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Sample records for acute assault-related injury

  1. Violent Reinjury and Mortality Among Youth Seeking Emergency Department Care for Assault-Related Injury A 2-Year Prospective Cohort Study

    PubMed Central

    Cunningham, Rebecca M.; Carter, Patrick M.; Ranney, Megan; Zimmerman, Marc A.; Blow, Fred C.; Booth, Brenda M.; Goldstick, Jason; Walton, Maureen A.

    2015-01-01

    IMPORTANCE Violence is a leading cause of morbidity and mortality among youth, with more than 700 000 emergency department (ED) visits annually for assault-related injuries. The risk for violent reinjury among high-risk, assault-injured youth is poorly understood. OBJECTIVE To compare recidivism for violent injury and mortality outcomes among drug-using, assault-injured youth (AI group) and drug-using, non–assault-injured control participants (non-AI group) presenting to an urban ED for care. DESIGN, SETTING, AND PARTICIPANTS Participants were enrolled in a prospective cohort study from December 2, 2009, through September 30, 2011, at an urban level I ED and followed up for 24 months. We administered validated measures of violence and substance use and mental health diagnostic interviews and reviewed medical records at baseline and at each point of follow-up (6, 12, 18, and 24 months). EXPOSURE Follow-up over 24 months. MAIN OUTCOMES AND MEASURES Use of ED services for assault or mortality measured from medical record abstraction supplemented with self-report. RESULTS We followed 349 AI and 250 non-AI youth for 24 months. Youth in the AI group had almost twice the risk for a violent injury requiring ED care within 2 years compared with the non-AI group (36.7% vs 22.4%; relative risk [RR], 1.65 [95% CI, 1.25-2.14]; P < .001). Two-year mortality was 0.8%. Poisson regression modeling identified female sex (RR, 1.30 [95% CI, 1.02-1.65]), assault-related injury (RR, 1.57 [95% CI, 1.19-2.04), diagnosis of a drug use disorder (RR, 1.29 [95% CI, 1.01-1.65]), and posttraumatic stress disorder (RR, 1.47 [95% CI, 1.09-1.97]) at the index visit as predictive of ED recidivism or death within 24 months. Parametric survival models demonstrated that assault-related injury (P < .001), diagnosis of posttraumatic stress disorder (P = .008), and diagnosis of a drug use disorder (P = .03) significantly shortened the expected waiting time until the first ED return visit for violence

  2. Acute kidney injury.

    PubMed

    Lang, Joanna; Zuber, Kim; Davis, Jane

    2016-04-01

    Acute kidney injury (AKI) complicates up to 20% of all hospital admissions. Responding to the increase in admissions, complications, mortality, morbidity, and cost of AKI, Kidney Disease: Improving Global Outcomes convened an expert panel to study the issue, review the literature, and publish guidelines to evaluate and treat patients with AKI in the acute setting. This article reviews those guidelines. PMID:27023656

  3. Acute Inhalation Injury

    PubMed Central

    Gorguner, Metin; Akgun, Metin

    2010-01-01

    Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

  4. Acute Kidney Injury.

    PubMed

    Zuk, Anna; Bonventre, Joseph V

    2016-01-01

    Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD). PMID:26768243

  5. Acute lung injury review.

    PubMed

    Tsushima, Kenji; King, Landon S; Aggarwal, Neil R; De Gorordo, Antonio; D'Alessio, Franco R; Kubo, Keishi

    2009-01-01

    The first report of acute respiratory distress syndrome (ARDS) was published in 1967, and even now acute lung injury (ALI) and ARDS are severe forms of diffuse lung disease that impose a substantial health burden all over the world. Recent estimates indicate approximately 190,000 cases per year of ALI in the United States each year, with an associated 74,500 deaths per year. Common causes of ALI/ARDS are sepsis, pneumonia, trauma, aspiration pneumonia, pancreatitis, and so on. Several pathologic stages of ALI/ARDS have been described: acute inflammation with neutrophil infiltration, fibroproliferative phase with hyaline membranes, with varying degrees of interstitial fibrosis, and resolution phase. There has been intense investigation into the pathophysiologic events relevant to each stage of ALI/ARDS, and much has been learned in the alveolar epithelial, endobronchial homeostasis, and alveolar cell immune responses, especially neutrophils and alveolar macrophages in an animal model. However, these effective results in the animal models are not equally adoptive to those in randomized, controlled trials. The clinical course of ALI/ARDS is variable with the likely pathophysiologic complexity of human ALI/ARDS. In 1994, the definition was recommended by the American-European Consensus Conference Committee, which facilitated easy nomination of patients with ALI/ARDS for a randomized, clinical trial. Here, we review the recent randomized, clinical trials of ALI/ARDS. PMID:19420806

  6. Hyperoxic Acute Lung Injury

    PubMed Central

    Kallet, Richard H; Matthay, Michael A

    2013-01-01

    Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies. PMID:23271823

  7. [Ascites and acute kidney injury].

    PubMed

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years. PMID:27571467

  8. Acute kidney injury.

    PubMed

    Patschan, Daniel; Müller, Gerhard Anton

    2015-01-01

    Acute kidney injury is a frequent and serious complication in hospitalized patients. Mortality rates have not substantially been decreased during the last 20 years. In most patients AKI results from transient renal hypoperfusion or ischemia. The consequences include tubular cell dysfunction/damage, inflammation of the organ, and post-ischemic microvasculopathy. The two latter events perpetuate kidney damage in AKI. Clinical manifestations result from diminished excretion of water, electrolytes, and endogenous / exogenous waste products. Patients are endangered by cardiovascular complications such as hypertension, heart failure, and arrhythmia. In addition, the whole organism may be affected by systemic toxification (uremia). The diagnostic approach in AKI involves several steps with renal biopsy inevitable in some patients. The current therapy focuses on preventing further kidney damage and on treatment of complications. Different pharmacological strategies have failed to significantly improve prognosis in AKI. If dialysis treatment becomes mandatory, intermittent and continuous renal replacement therapies are equally effective. Thus, new therapies are urgently needed in order to reduce short- and long-term outcome in AKI. In this respect, stem cell-based regimens may offer promising perspectives. PMID:25618438

  9. Acute kidney injury

    PubMed Central

    Müller, Gerhard Anton

    2015-01-01

    Abstract: Acute kidney injury is a frequent and serious complication in hospitalized patients. Mortality rates have not substantially been decreased during the last 20 years. In most patients AKI results from transient renal hypoperfusion or ischemia. The consequences include tubular cell dysfunction/damage, inflammation of the organ, and post-ischemic microvasculopathy. The two latter events perpetuate kidney damage in AKI. Clinical manifestations result from diminished excretion of water, electrolytes, and endogenous / exogenous waste products. Patients are endangered by cardiovascular complications such as hypertension, heart failure, and arrhythmia. In addition, the whole organism may be affected by systemic toxification (uremia). The diagnostic approach in AKI involves several steps with renal biopsy inevitable in some patients. The current therapy focuses on preventing further kidney damage and on treatment of complications. Different pharmacological strategies have failed to significantly improve prognosis in AKI. If dialysis treatment becomes mandatory, intermittent and continuous renal replacement therapies are equally effective. Thus, new therapies are urgently needed in order to reduce short- and long-term outcome in AKI. In this respect, stem cell-based regimens may offer promising perspectives. PMID:25618438

  10. Acute kidney injury in children.

    PubMed

    Merouani, A; Flechelles, O; Jouvet, P

    2012-04-01

    Acute kidney injury (AKI) affects 5% of critically ill hospitalized children and is a risk factor for increased morbidity and mortality. The current review focuses on new definitions of acute kidney injury, standardized to reflect the entire spectrum of the disease, as well as on ongoing research to identify early biomarkers of kidney injury. Its also provides an overview of current practice and available therapies, with emphasis on new strategies for the prevention and pharmacological treatment of diarrhea-associated hemolytic uremic syndrome. Furthermore, a decision-making algorithm is presented for the use of renal replacement therapies in critically ill children with AKI. PMID:22495187

  11. Acute injuries in Taekwondo.

    PubMed

    Schlüter-Brust, K; Leistenschneider, P; Dargel, J; Springorum, H P; Eysel, P; Michael, J W-P

    2011-08-01

    Although Taekwondo is becoming an increasingly popular sport, there is a lack of reliable epidemiologic data on Taekwondo injuries. To perform an epidemiologic study on the variety of types of injury in professional and amateur Taekwondo athletes and to find a relation between Taekwondo style, skill level, weight-class and warm-up routine and the occurrence of injuries, we analysed the injury data using a 7-page questionnaire from a total of 356 Taekwondo athletes who were randomly selected. Overall, we registered a total of 2,164 injuries in 356 athletes. Most traumas were contusions and sprains in the lower extremities. Professional Taekwondo athletes have an increased risk of injury in comparison to recreational athletes. Taekwondo style, weight class and tournament frequency have an influence on the athlete's injury profile. Warm-up routines were found to have a positive effect on injury rates. Overall, Taekwondo may be considered a rather benign activity, if injuries during Taekwondo tournaments can be avoided. If not, Taekwondo can result in serious musculoskeletal problems. PMID:21563037

  12. Acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Singh, Sarvesh Pal

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074

  13. Autophagy in acute brain injury.

    PubMed

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Blomgren, Klas; Kroemer, Guido

    2016-08-01

    Autophagy is an evolutionarily ancient mechanism that ensures the lysosomal degradation of old, supernumerary or ectopic cytoplasmic entities. Most eukaryotic cells, including neurons, rely on proficient autophagic responses for the maintenance of homeostasis in response to stress. Accordingly, autophagy mediates neuroprotective effects following some forms of acute brain damage, including methamphetamine intoxication, spinal cord injury and subarachnoid haemorrhage. In some other circumstances, however, the autophagic machinery precipitates a peculiar form of cell death (known as autosis) that contributes to the aetiology of other types of acute brain damage, such as neonatal asphyxia. Here, we dissect the context-specific impact of autophagy on non-infectious acute brain injury, emphasizing the possible therapeutic application of pharmacological activators and inhibitors of this catabolic process for neuroprotection. PMID:27256553

  14. Acute Shoulder Injuries in Adults.

    PubMed

    Monica, James; Vredenburgh, Zachary; Korsh, Jeremy; Gatt, Charles

    2016-07-15

    Acute shoulder injuries in adults are often initially managed by family physicians. Common acute shoulder injuries include acromioclavicular joint injuries, clavicle fractures, glenohumeral dislocations, proximal humerus fractures, and rotator cuff tears. Acromioclavicular joint injuries and clavicle fractures mostly occur in young adults as the result of a sports injury or direct trauma. Most nondisplaced or minimally displaced injuries can be treated conservatively. Treatment includes pain management, short-term use of a sling for comfort, and physical therapy as needed. Glenohumeral dislocations can result from contact sports, falls, bicycle accidents, and similar high-impact trauma. Patients will usually hold the affected arm in their contralateral hand and have pain with motion and decreased motion at the shoulder. Physical findings may include a palpable humeral head in the axilla or a dimple inferior to the acromion laterally. Reduction maneuvers usually require intra-articular lidocaine or intravenous analgesia. Proximal humerus fractures often occur in older patients after a low-energy fall. Radiography of the shoulder should include a true anteroposterior view of the glenoid, scapular Y view, and axillary view. Most of these fractures can be managed nonoperatively, using a sling, early range-of-motion exercises, and strength training. Rotator cuff tears can cause difficulty with overhead activities or pain that awakens the patient from sleep. On physical examination, patients may be unable to hold the affected arm in an elevated position. It is important to recognize the sometimes subtle signs and symptoms of acute shoulder injuries to ensure proper management and timely referral if necessary. PMID:27419328

  15. Acute Kidney Injury in Cirrhosis.

    PubMed

    Karvellas, Constantine J; Durand, Francois; Nadim, Mitra K

    2015-10-01

    Acute kidney injury (AKI) is a frequent complication of end-stage liver disease, especially in those with acute-on-chronic liver failure, occurring in up to 50% of hospitalized patients with cirrhosis. There is no specific blood or urine biomarker that can reliably identify the cause of AKI in cirrhotic patients. This review examines studies used to assess renal dysfunction in cirrhotic patients including new diagnostic criteria and potential novel biomarkers. Although biomarker development to differentiate the cause of AKI in cirrhosis has promise, the utility of biomarkers to determine irreversible renal dysfunction with liver transplant remains lacking, warranting further investigation. PMID:26410141

  16. Epigenetics in acute kidney injury

    PubMed Central

    Tang, Jinhua; Zhuang, Shougang

    2015-01-01

    Purpose of review Recent advances in epigenetics indicate the involvement of several epigenetic modifications in the pathogenesis of acute kidney injury (AKI). The purpose of this review is to summarize our understanding of recent advances in epigenetic regulation of AKI and provide mechanistic insight into the role of acetylation, methylation, and microRNA expression in the pathological processes of AKI. Recent findings Enhancement of protein acetylation by pharmacological inhibition of histone deacetylases (HDACs) leads to more severe tubular injury and impairment of renal structural and functional recovery. The changes in promoter DNA methylation occur in the kidney with ischemia/reperfusion. microRNA expression is associated with regulation of both renal injury and regeneration after AKI. Summary Recent studies on epigenetic regulation indicate that acetylation, methylation, and microRNA expression are critically implicated in the pathogenesis of AKI. Strategies targeting epigenetic processes may hold a therapeutic potential for patients with AKI. PMID:26050122

  17. Pathophysiology of Acute Kidney Injury

    PubMed Central

    Basile, David P.; Anderson, Melissa D.; Sutton, Timothy A.

    2014-01-01

    Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. PMID:23798302

  18. Biomarkers of Acute Kidney Injury

    PubMed Central

    Vaidya, Vishal S.; Ferguson, Michael A.; Bonventre, Joseph V.

    2009-01-01

    Acute kidney injury (AKI) is a common condition with a high risk of death. The standard metrics used to define and monitor the progression of AKI, such as serum creatinine and blood urea nitrogen levels, are insensitive, nonspecific, and change significantly only after significant kidney injury and then with a substantial time delay. This delay in diagnosis not only prevents timely patient management decisions, including administration of putative therapeutic agents, but also significantly affects the preclinical evaluation of toxicity thereby allowing potentially nephrotoxic drug candidates to pass the preclinical safety criteria only to be found to be clinically nephrotoxic with great human costs. Studies to establish effective therapies for AKI will be greatly facilitated by two factors: (a) development of sensitive, specific, and reliable biomarkers for early diagnosis/prognosis of AKI in preclinical and clinical studies, and (b) development and validation of high-throughput innovative technologies that allow rapid multiplexed detection of multiple markers at the bedside. PMID:17937594

  19. Exenatide induced acute kidney injury.

    PubMed

    Aijazi, Ishma; Abdulla, Fadhil M; Zuberi, Beyla J; Elhassan, Ahmed

    2014-01-01

    Exenatide is an incretin mimetic. It was approved by the federal drug authority in 2005 for the treatment of type-2 diabetes. Since it is a relatively new medicine clinicians have limited experience with regards to its side effects and safety profile. We report a 47 year old lady who presented with exenatide associated acute kidney injury. She had type-2 diabetes for 10 years with mild micro albuminuria and normal renal functions. She was also taking a stable dose of metformin, gliclazide, angiotensin converting enzyme inhibitor and diuretic for over a year and there was no history of any recent use of non-steroid anti-inflammatory medications. One week after starting exenatide, she developed severe vomiting, followed by hypotension. She presented with acute renal insufficiency and severe lactic acidosis and had to be dialyzed on emergency basis. To our knowledge this is probably the first case reported in the local United Arab Emirate (U.A.E) population. PMID:25672206

  20. [Acute kidney injury in children].

    PubMed

    Amira-Peco-Antić; Paripović, Dusan

    2014-01-01

    Acute kidney injury (AKI) is a clinical condition considered to be the consequence of a sudden decrease (> 25%) or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN) are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary) diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis) jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP). Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients. PMID:25033598

  1. The cell cycle and acute kidney injury

    PubMed Central

    Price, Peter M.; Safirstein, Robert L.; Megyesi, Judit

    2009-01-01

    Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used to control and perhaps to prevent acute kidney injury. This review is written to address the correlation between cellular life and death in kidney tubules, especially in acute kidney injury. PMID:19536080

  2. Rock Climbing Injuries: Acute and Chronic Repetitive Trauma.

    PubMed

    Chang, Connie Y; Torriani, Martin; Huang, Ambrose J

    2016-01-01

    Rock climbing has increased in popularity as a sport, and specific injuries related to its practice are becoming more common. Chronic repetitive injuries are more common than acute injuries, although acute injuries tend to be more severe. We review both acute and chronic upper and lower extremity injuries. Understanding the injury pattern in rock climbers is important for accurate diagnosis. PMID:26360057

  3. Nephrology Update: Acute Kidney Injury.

    PubMed

    Sarabu, Nagaraju; Rahman, Mahboob

    2016-05-01

    Acute kidney injury (AKI) refers to any acute decrease in glomerular filtration rate, regardless of etiology. Staging of AKI has been recommended to stratify AKI patients according to severity of the condition, based on serum creatinine level and urine output. Classification of AKI into prerenal, intrinsic renal, and postrenal etiologies is helpful in differential diagnosis and management. AKI in hospitalized patients typically occurs due to decreased renal perfusion. Drug-induced, contrast-associated, postoperative, and sepsis-associated AKI also can occur. Clinical assessment of a patient with AKI involves a medical record review, thorough history and physical examination, urinary and blood tests, renal imaging, and, in some instances, renal biopsy. Contrast-induced nephropathy is a common iatrogenic etiology of AKI associated with administration of intravenous iodinated contrast media. Measures to prevent AKI should be taken before administration of intravenous iodinated contrast. AKI can result in many short- and long-term complications, including chronic kidney disease and end-stage renal disease. Appropriate treatment of AKI patients involves management of the underlying etiology, when possible, and use of nondialytic and dialytic therapies. PMID:27163760

  4. Targeting Iron Homeostasis in Acute Kidney Injury.

    PubMed

    Walker, Vyvyca J; Agarwal, Anupam

    2016-01-01

    Iron is an essential metal involved in several major cellular processes required to maintain life. Because of iron's ability to cause oxidative damage, its transport, metabolism, and storage is strictly controlled in the body, especially in the small intestine, liver, and kidney. Iron plays a major role in acute kidney injury and has been a target for therapeutic intervention. However, the therapies that have been effective in animal models of acute kidney injury have not been successful in human beings. Targeting iron trafficking via ferritin, ferroportin, or hepcidin may offer new insights. This review focuses on the biology of iron, particularly in the kidney, and its implications in acute kidney injury. PMID:27085736

  5. [Perioperative acute kidney injury and failure].

    PubMed

    Chhor, Vibol; Journois, Didier

    2014-04-01

    Perioperative period is very likely to lead to acute renal failure because of anesthesia (general or perimedullary) and/or surgery which can cause acute kidney injury. Characterization of acute renal failure is based on serum creatinine level which is imprecise during and following surgery. Studies are based on various definitions of acute renal failure with different thresholds which skewed their comparisons. The RIFLE classification (risk, injury, failure, loss, end stage kidney disease) allows clinicians to distinguish in a similar manner between different stages of acute kidney injury rather than using a unique definition of acute renal failure. Acute renal failure during the perioperative period can mainly be explained by iatrogenic, hemodynamic or surgical causes and can result in an increased morbi-mortality. Prevention of this complication requires hemodynamic optimization (venous return, cardiac output, vascular resistance), discontinuation of nephrotoxic drugs but also knowledge of the different steps of the surgery to avoid further degradation of renal perfusion. Diuretics do not prevent acute renal failure and may even push it forward especially during the perioperative period when venous retourn is already reduced. Edema or weight gain following surgery are not correlated with the vascular compartment volume, much less with renal perfusion. Treatment of perioperative acute renal failure is similar to other acute renal failure. Renal replacement therapy must be mastered to prevent any additional risk of hemodynamic instability or hydro-electrolytic imbalance. PMID:24656890

  6. Management of acute spinal cord injury.

    PubMed

    Wagner, F C

    1977-06-01

    Based on the experience with 58 patients with acute spinal cord injuries, a system for rapidly evaluating such patients has been developed. With the knowledge that has been acquired clinically and experimentally of spinal cord injury and with the information provided by laminography and by either air or Pantopaque myelography, a reasonably certain diagnosis of the type of spinal cord injury may be made. Treatment designed to restore neurological function may then be instituted promptly. PMID:882906

  7. Acute forefoot and midfoot injuries.

    PubMed

    Laird, R Clinton

    2015-04-01

    Forefoot and midfoot injuries in the athlete are common. Injuries of the digits include subungual hematomas and fractures. Metatarsal fractures occur frequently in sports, and their treatments range greatly. Hyperflexion and extension injuries about the first metatarsophalangeal joint can be very debilitating. Midfoot sprains and fractures require a high index of suspicion for diagnosis. PMID:25804712

  8. Animal models of acute lung injury

    PubMed Central

    Matute-Bello, Gustavo; Frevert, Charles W.; Martin, Thomas R.

    2008-01-01

    Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury. PMID:18621912

  9. Acute kidney injury due to decompression illness.

    PubMed

    Viecelli, Andrea; Jamboti, Jagadish; Waring, Andrew; Banham, Neil; Ferrari, Paolo

    2014-08-01

    Decompression illness is a rare but serious complication of diving caused by intravascular or extravascular gas bubble formation. We report the first case of acute kidney injury in a 27-year-old diver following three rapid ascents. He presented with transient neurological symptoms and abdominal pain followed by rapidly progressive acute kidney injury (creatinine peak 1210 µmol/L) due to arterial air emboli. He received supportive care and 100% oxygen followed by hyperbaric therapy and recovered fully. Arterial air emboli caused by rapid decompression can affect multiple organs including the kidneys. Early transfer to a hyperbaric unit is important as complications may present delayed. PMID:25852912

  10. Acute kidney injury due to decompression illness

    PubMed Central

    Viecelli, Andrea; Jamboti, Jagadish; Waring, Andrew; Banham, Neil; Ferrari, Paolo

    2014-01-01

    Decompression illness is a rare but serious complication of diving caused by intravascular or extravascular gas bubble formation. We report the first case of acute kidney injury in a 27-year-old diver following three rapid ascents. He presented with transient neurological symptoms and abdominal pain followed by rapidly progressive acute kidney injury (creatinine peak 1210 µmol/L) due to arterial air emboli. He received supportive care and 100% oxygen followed by hyperbaric therapy and recovered fully. Arterial air emboli caused by rapid decompression can affect multiple organs including the kidneys. Early transfer to a hyperbaric unit is important as complications may present delayed. PMID:25852912

  11. CAPing inflammation and acute kidney injury.

    PubMed

    Inoue, Tsuyoshi; Rosin, Diane L; Okusa, Mark D

    2016-09-01

    The cholinergic anti-inflammatory pathway has been shown to modulate inflammation in disease models such as rheumatoid arthritis and inflammatory bowel disease. A recent study demonstrated a protective effect of vagus nerve stimulation with activation of the cholinergic anti-inflammatory pathway in the ischemia reperfusion model of acute kidney injury. PMID:27521104

  12. A SCUBA diver with acute kidney injury.

    PubMed

    Gleeson, Patrick James; Kelly, Yvelynne; Ni Sheaghdha, Eadaoin; Lappin, David

    2015-01-01

    An otherwise healthy young man was transferred to our hospital after a diving incident. He had made an uncontrolled ascent from 10 m. On arrival he appeared well. No hypotensive episodes occurred during the transfer. He denied having arthralgias, back pain, dyspnoea or neurological symptoms. Laboratory investigations revealed acutely elevated creatinine (170 µmol/L) and creatine kinase (909 U/L). Radiology was consistent with a focus of pulmonary barotrauma and intrinsic renal disease. Creatine kinase is a marker of arterial gas embolism (AGE). We determined that our patient suffered acute kidney injury as a result of gas embolisation to his renal vasculature from an area of pulmonary barotrauma. Creatinine fell the following day in response to aggressive intravenous fluids. This is the first reported case of acute kidney injury secondary to AGE. Biochemical studies should be part of the routine assessment of patients involved in diving incidents. PMID:25948841

  13. Acute kidney injury: current concepts and new insights

    PubMed Central

    Koza, Yavuzer

    2016-01-01

    Abstract: Background: Acute kidney injury, which was previously named as acute renal failure, is a complex clinical disorder and continues to be associated with poor outcomes. It is frequently seen in hospitalized patients, especially in critically ill patients. The primary causes of acute kidney injury are divided into three categories: prerenal, intrinsic renal and postrenal. The definition and staging of acute kidney injury are mainly based on the risk, injury, failure, loss, end-stage kidney disease (RIFLE) criteria and the acute kidney injury network (AKIN) criteria, which have previously been defined. However the clinical utility of these criteria is still uncertain. Several biomarkers such as Cystatin C and neutrophil gelatinase-associated lipocalin have been suggested for the diagnosis, severity classification and most importantly, the modification of outcome in acute kidney injury. Methods: Current literature on the definition, biomarkers, management and epidemiology of acute kidney injury was reviewed by searching keywords in Medline and PubMed databases. Results: The epidemiology, pathophysiology and diagnosis of acute kidney injury were discussed. The clinical implications of novel biomarkers and management of acute kidney injury were also discussed. Conclusions: The current definitions of acute kidney injury are based on the RIFLE, AKIN and KDIGO criteria. Although these criteria have been widely validated, some of limitations are still remain. Since acute kidney injury is common and harmful, all preventive measures should be taken to avoid its occurrence. Currently, there is no a definitive role for novel biomarkers. PMID:26804946

  14. Acute Kidney Injury in the Surgical Patient.

    PubMed

    Hobson, Charles; Singhania, Girish; Bihorac, Azra

    2015-10-01

    Perioperative acute kidney injury (AKI) is a common, morbid, and costly surgical complication. Current efforts to understand and manage AKI in surgical patients focus on prevention, mitigation of further injury when AKI has occurred, treatment of associated conditions, and facilitation of renal recovery. Lesser severity AKI is now understood to be much more common, and more morbid, than was previously thought. The ability to detect AKI within hours of onset would be helpful in protecting the kidney and in preserving renal function, and several imaging and biomarker modalities are currently being evaluated. PMID:26410139

  15. First aid for acute sports injuries.

    PubMed

    Bull, R C

    1987-09-01

    This article deals with management of acute sports injuries on the field or on the ice and in the dressing room or in the arena's first-aid room. Its most vital message is "Be prepared". A team approach and suitable ambulance and hospital back-up are mandatory. Individual management of a specific acute injury should be approached with a practice plan. Collars, splints, back board, doctor's bag, ambu bag, suture tray and emergency medications should be at hand. Care must be taken that no long-term harm befalls the player. The attending physician must be knowledgeable about preventive equipment and immediate institution of rehabilitation procedures, and must try to inform the coach or trainer and parent as to when the athlete can safely return to play. It is important that the athlete not return to play until he/she is 100% fit. PMID:21263977

  16. Sodium hypochlorite-induced acute kidney injury.

    PubMed

    Peck, Brandon W; Workeneh, Biruh; Kadikoy, Huseyin; Abdellatif, Abdul

    2014-03-01

    Sodium hypochlorite (bleach) is commonly used as an irrigant during dental procedures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo-chlorite has never been implicated as a cause of an acute kidney injury (AKI). In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis. PMID:24626008

  17. Ischaemic Markers in Acute Hepatic Injury

    PubMed Central

    Jena, Sushanta Kumar; Nanda, Rachita; Mangaraj, Manaswini; Nayak, Parsuram

    2016-01-01

    Introduction Hepatic injury of varied aetiology may progress to Acute Liver Failure (ALF). Compromised microcirculation is thought to be a deciding factor of hepatic hypoxia may be involved in disease progression that needs early detection. Ischaemia markers like serum Ischaemia- modified albumin (IMA), ALT-LDH ratio and ALT-LDH index have been suggested for its detection at early stage. Aim To find out the association of Ischaemia markers like serum IMA, ALT-LDH ratio and ALT-LDH index in acute hepatic injury cases. Materials and Methods Forty one diagnosed acute liver injury cases of varied aetiology admitted in Department of Medicine, and Gastroenterology of SCB Medical College, Cuttack were enrolled in the study along with 30 age and sex matched healthy controls. Blood collected at time of admission and at time of discharge (1st day and 7th day) were evaluated for FPG, RFT, LFT, Serum Albumin along with serum LDH, IMA, PT-INR and platelet count. Result Serum bilirubin, hepatic enzymes, IMA, PT-INR was more markedly raised in cases than controls on the 1st day of admission. ALT-LDH ratio and index were significantly low in complicated cases. However, on responding to treatment the ALT-LDH index on 7th day registered a rise in comparison to the 1st day, while serum IMA revealed an insignificant decline showing improvement in hepatic hypoxia. ALT-LDH ratio remains more or less same on response to treatment. Conclusion Serum IMA and ALT-LDH Index reveals association with disease process in Acute Hepatic Injury cases both clinically and biochemically and can be used as supportive parameters for the diagnosis of disease process. PMID:27190791

  18. Dengue-associated acute kidney injury

    PubMed Central

    Oliveira, João Fernando Picollo; Burdmann, Emmanuel A.

    2015-01-01

    Dengue is presently the most relevant viral infection transmitted by a mosquito bite that represents a major threat to public health worldwide. Acute kidney injury (AKI) is a serious and potentially lethal complication of this disease, and the actual incidence is unknown. In this review, we will assess the most relevant epidemiological and clinical data regarding dengue and the available evidence on the frequency, etiopathogenesis, outcomes and treatment of dengue-associated AKI. PMID:26613023

  19. Modulation of acute lung injury by integrins.

    PubMed

    Sheppard, Dean

    2012-07-01

    Acute lung injury is a common disorder with a high mortality rate, but previous efforts to develop drugs to treat this disorder have been unsuccessful. In an effort to develop more effective treatments, we have been studying the molecular pathways that regulate the dysfunction of alveolar epithelial cells and endothelial cells that serve as a final common pathway leading to alveolar flooding. Using integrin subunit knockout mice and antibodies we developed by immunizing these mice, we have found important and distinct roles for the αvβ6 integrin on epithelial cells and the αvβ5 integrin on endothelial cells in mediating increases in alveolar permeability in multiple models of acute lung injury. We have also found therapeutic effects of αvβ5 inhibition in two models of septic shock even when the antibody was administered to animals that were obviously ill. These results identify αvβ6 and αvβ5 as promising therapeutic targets for the treatment of acute lung injury and septic shock. PMID:22802286

  20. Acute kidney injury due to rhabdomyolysis.

    PubMed

    Lima, Rafael Siqueira Athayde; da Silva Junior, Geraldo Bezerra; Liborio, Alexandre Braga; Daher, Elizabeth De Francesco

    2008-09-01

    Rhabdomyolysis is a clinical and biochemical syndrome that occurs when skeletal muscle cells disrupt and release creatine phosphokinase (CK), lactate dehydrogenase (LDH), and myoglobin into the interstitial space and plasma. The main causes of rhabdomyolysis include direct muscular injury, strenuous exercise, drugs, toxins, infections, hyperthermia, seizures, meta-bolic and/or electrolyte abnormalities, and endocrinopathies. Acute kidney injury (AKI) occurs in 33-50% of patients with rhabdomyolysis. The main pathophysiological mechanisms of renal injury are renal vasoconstriction, intraluminal cast formation, and direct myoglobin toxicity. Rhabdo-myolysis can be asymptomatic, present with mild symptoms such as elevation of muscular en-zymes, or manifest as a severe syndrome with AKI and high mortality. Serum CK five times higher than the normal value usually confirms rhabdomyolysis. Early diagnosis and saline volume expansion may reduce the risk of AKI. Further studies are necessary to establish the importance of bicarbonate and mannitol in the prevention of AKI due to rhabdomyolysis. PMID:18711286

  1. Antifibrinolytic drugs for acute traumatic injury.

    PubMed

    McCaul, Michael; Kredo, Tamara

    2016-08-01

    In South Africa, trauma is a major concern, with violence and road traffic accidents being the fifth and seventh leading causes of death, respectively. Antifibrinolytic agents have been used in trauma and major surgery to prevent fibrinolysis and reduce blood loss. We highlight an updated Cochrane review investigating the effect of antifibrinolytic drugs in patients with acute traumatic injury. The review authorsconducted comprehensive literature searches in January 2015 with regard to all randomised controlled trials comparing antifibrinolytic agents after acute traumatic injury. Three randomised controlled trials, of which two (n=20 451) assessed the effect of tranexamic acid (TXA), were included. The authors concluded that TXA safely reduces mortality in trauma with bleeding without increasing the risk ofadverse events. TXA should be administered as early as possible, and within 3 hours of injury. There is still uncertainty with regard to the effect of TXA on patients with traumatic brain injury; however, ongoing randomised controlled trials should shed more light on this. PMID:27499400

  2. Interleukin-1 and acute brain injury

    PubMed Central

    Murray, Katie N.; Parry-Jones, Adrian R.; Allan, Stuart M.

    2015-01-01

    Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review. PMID:25705177

  3. Epidemiology of Overuse and Acute Injuries Among Competitive Collegiate Athletes

    PubMed Central

    Yang, Jingzhen; Tibbetts, Abigail S.; Covassin, Tracey; Cheng, Gang; Nayar, Saloni; Heiden, Erin

    2012-01-01

    Context: Although overuse injuries are gaining attention, epidemiologic studies on overuse injuries in male and female collegiate athletes are lacking. (70.7%) acute injuries were reported. The overall injury rate was Objective: To report the epidemiology of overuse injuries sustained by collegiate athletes and to compare the rates of overuse and acute injuries. Design: Descriptive epidemiology study. Setting: A National Collegiate Athletic Association Division I university. Patients or Other Participants: A total of 1317 reported injuries sustained by 573 male and female athletes in 16 collegiate sports teams during the 2005–2008 seasons. Main Outcome Measure(s): The injury and athlete-exposure (AE) data were obtained from the Sports Injury Monitoring System. An injury was coded as either overuse or acute based on the nature of injury. Injury rate was calculated as the total number of overuse (or acute) injuries during the study period divided by the total number of AEs during the same period. Results: A total of 386 (29.3%) overuse injuries and 931 63.1 per 10000 AEs. The rate ratio (RR) of acute versus overuse injuries was 2.34 (95% confidence interval [CI] = 2.05, 2.67). Football had the highest RR (RR = 8.35, 95% CI = 5.38, 12.97), and women's rowing had the lowest (RR = 0.75, 95% CI = 0.51, 1.10). Men had a higher acute injury rate than women (49.8 versus 38.6 per 10000 AEs). Female athletes had a higher rate of overuse injury than male athletes (24.6 versus 13.2 per 10000 AEs). More than half of the overuse injuries (50.8%) resulted in no time loss from sport. Conclusions: Additional studies are needed to examine why female athletes are at greater risk for overuse injuries and identify the best practices for prevention and rehabilitation of overuse injuries. PMID:22488286

  4. Inflammatory sequences in acute pulmonary radiation injury.

    PubMed Central

    Slauson, D. O.; Hahn, F. F.; Benjamin, S. A.; Chiffelle, T. L.; Jones, R. K.

    1976-01-01

    The histopathologic events in the developing acute pulmonary inflammatory reaction to inhaled particles of Yttrium 90 are detailed. In animals that died or were sacrificed during the first year after inhalation exposure, microscopic findings of acute inflammation predominated and included vascular congestion; stasis, focal hemorrhage; edema; various inflammatory cell infiltrates; cytolysis and desquamation of bronchiolar and alveolar epithelium followed by regeneration; vascular injury and repair; and the eventual development of pulmonary fibrosis. Accumulation of alveolar fibrin deposits was an additional characteristic, though not a constant feature of the early stages of radiation pneumonitis. In addition to the direct effects of radiation on pulmonary cell populations, the histopathologic findings were suggestive of diverse activation of various cellular and humoral mediation systems in their pathogenesis. The potential interrelationships of systems responsible for increased vascular permeability, coagulation and fibrinolysis, chemotaxis, and direct cellular injury were discussed and related to the pathogenesis of the microscopic findings characteristic of early pulmonary radiation injury. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:1258976

  5. Acute Kidney Injury in Patients with Cirrhosis

    PubMed Central

    Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.

    2015-01-01

    Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK. PMID:26623266

  6. [Drug-induced acute kidney injury].

    PubMed

    Derungs, Adrian

    2015-12-01

    Due to their physiological function, the kidneys are exposed to high concentrations of numerous drugs and their metabolites, making them vulnerable to drug-related injuries. This article provides an overview of the pathophysiological mechanisms involved in nephrotoxicity, the most common nephrotoxic drugs, and the risk factors for the occurrence of drug-induced acute kidney injuries. NSAIDs, diuretics, ACE inhibitors, and angiotensin II receptor blockers (ARBs} are the most frequent prerenal causes of an acute elevation in creatinine levels. Primary vascular damage arises from thrombotic microangiopathy (e. g. due to cic/osporin, tacrolimus, muromonab-CD3, mitomycin C, quinine, ticlopidine, clopidogrel}. Anticoagulants and thrombolytic medications lead to secondary blood vessel damage by cholesterol emboli, embolism of thrombus material into the periphery or bleeding. Tubulopathies can be observed on treatment with ifosfamide and cisplatin (rarely with cyclophosphamide or carboplatin), aminoglycosides, vancomycin, and radiocontrast agents. Immunological mechanisms underlie interstitial nephritides, which are induced by drugs in about 85% of cases. In drug-induced glomerulopathies;- renal biopsy allows closer identification of the triggering medication. Drug-induced systemic lupus erythematosus (SLE} represents a special form of immune complex glomerulonephritis and can be triggered by procainamide, hydralazine, isoniazid, methyldopa, quinidine, chlorpromazine, and propylthiouracil. Crystal-induced kidney injury is caused by precipitation of drugs (e. g. aciclovir, sulfonamide antibiotics, methotrexate, indinavir) in the renal tubules and the urine-conducting organs with consecutive obstruction thereof. PMID:26654816

  7. Acute kidney injury in patients with acute coronary syndromes.

    PubMed

    Marenzi, Giancarlo; Cosentino, Nicola; Bartorelli, Antonio L

    2015-11-01

    Acute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACSs). This condition has a complex pathogenesis, an incidence that can reach 30% and it is associated with higher short-term and long-term morbidity and mortality. Nevertheless, AKI is still characterised by lack of a single accepted definition, unclear pathophysiology understanding and insensitive diagnostic tools that make its detection difficult, particularly in the setting of ACS. Recent data suggested that patients with AKI during ACS, even those in whom renal function seems to fully recover, face an increased, persisting risk of future AKI and may develop chronic kidney disease. Thus, in these patients, nephrology follow-up, after hospital discharge, and secondary preventive measures should possibly be implemented. In this review, we aim at providing a framework of knowledge to increase cardiologists' awareness of AKI, with the goal of improving the outcome of patients with ACS. PMID:26243789

  8. Acute kidney injury: A rare cause.

    PubMed

    Mendonca, Satish; Barki, Satish; Mishra, Mayank; Kumar, R S V; Gupta, Devika; Gupta, Pooja

    2015-09-01

    We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering. PMID:26354573

  9. Clinical Scenarios in Acute Kidney Injury: Parenchymal Acute Kidney Injury-Tubulo-Interstitial Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria; Ronco, Claudio

    2016-01-01

    Acute tubular necrosis (ATN) is the most common type of acute kidney injury (AKI) related to parenchymal damage (90% of cases). It may be due to a direct kidney injury, such as sepsis, drugs, toxins, contrast media, hemoglobinuria and myoglobinuria, or it may be the consequence of a prolonged systemic ischemic injury. Conventional ultrasound (US) shows enlarged kidneys with hypoechoic pyramids. Increased volume is largely sustained by the increase of anteroposterior diameter, while longitudinal axis usually maintains its normal length. Despite the role of color Doppler in AKI still being debated, many studies demonstrate that renal resistive indexes (RIs) vary on the basis of primary disease. Moreover, several studies assessed that higher RI values are predictive of persistent AKI. Nevertheless, due to the marked heterogeneity among the studies, further investigations focused on timing of RI measurement and test performances are needed. Acute interstitial nephritis is also a frequent cause of AKI, mainly due to non-steroidal anti-inflammatory drugs and antibiotics administration. The development of acute interstitial nephritis is due to an immunological reaction against nephritogenic exogenous antigens, processed by tubular cells. In acute interstitial nephritis, as well as in ATN, conventional US does not allow a definitive diagnosis. Kidneys appear enlarged and widely hyperechoic due to interstitial edema and inflammatory infiltration. Also, in this condition, hemodynamic changes are closely correlated to the severity and the progression of the anatomical damage. PMID:27169885

  10. Thaliporphine derivative improves acute lung injury after traumatic brain injury.

    PubMed

    Chen, Gunng-Shinng; Huang, Kuo-Feng; Huang, Chien-Chu; Wang, Jia-Yi

    2015-01-01

    Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI. PMID:25705683

  11. Acute complications of spinal cord injuries.

    PubMed

    Hagen, Ellen Merete

    2015-01-18

    The aim of this paper is to give an overview of acute complications of spinal cord injury (SCI). Along with motor and sensory deficits, instabilities of the cardiovascular, thermoregulatory and broncho-pulmonary system are common after a SCI. Disturbances of the urinary and gastrointestinal systems are typical as well as sexual dysfunction. Frequent complications of cervical and high thoracic SCI are neurogenic shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperature control and disturbance of sweating, vasodilatation and autonomic dysreflexia. Autonomic dysreflexia is an abrupt, uncontrolled sympathetic response, elicited by stimuli below the level of injury. The symptoms may be mild like skin rash or slight headache, but can cause severe hypertension, cerebral haemorrhage and death. All personnel caring for the patient should be able to recognize the symptoms and be able to intervene promptly. Disturbance of respiratory function are frequent in tetraplegia and a primary cause of both short and long-term morbidity and mortality is pulmonary complications. Due to physical inactivity and altered haemostasis, patients with SCI have a higher risk of venous thromboembolism and pressure ulcers. Spasticity and pain are frequent complications which need to be addressed. The psychological stress associated with SCI may lead to anxiety and depression. Knowledge of possible complications during the acute phase is important because they may be life threatening and/ or may lead to prolonged rehabilitation. PMID:25621207

  12. Human models of acute lung injury

    PubMed Central

    Proudfoot, Alastair G.; McAuley, Danny F.; Griffiths, Mark J. D.; Hind, Matthew

    2011-01-01

    Acute lung injury (ALI) is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome. PMID:21357760

  13. Acute complications of spinal cord injuries

    PubMed Central

    Hagen, Ellen Merete

    2015-01-01

    The aim of this paper is to give an overview of acute complications of spinal cord injury (SCI). Along with motor and sensory deficits, instabilities of the cardiovascular, thermoregulatory and broncho-pulmonary system are common after a SCI. Disturbances of the urinary and gastrointestinal systems are typical as well as sexual dysfunction. Frequent complications of cervical and high thoracic SCI are neurogenic shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperature control and disturbance of sweating, vasodilatation and autonomic dysreflexia. Autonomic dysreflexia is an abrupt, uncontrolled sympathetic response, elicited by stimuli below the level of injury. The symptoms may be mild like skin rash or slight headache, but can cause severe hypertension, cerebral haemorrhage and death. All personnel caring for the patient should be able to recognize the symptoms and be able to intervene promptly. Disturbance of respiratory function are frequent in tetraplegia and a primary cause of both short and long-term morbidity and mortality is pulmonary complications. Due to physical inactivity and altered haemostasis, patients with SCI have a higher risk of venous thromboembolism and pressure ulcers. Spasticity and pain are frequent complications which need to be addressed. The psychological stress associated with SCI may lead to anxiety and depression. Knowledge of possible complications during the acute phase is important because they may be life threatening and/ or may lead to prolonged rehabilitation. PMID:25621207

  14. Electrophysiologic monitoring in acute brain injury.

    PubMed

    Claassen, Jan; Vespa, Paul

    2014-12-01

    To determine the optimal use and indications of electroencephalography (EEG) in critical care management of acute brain injury (ABI). An electronic literature search was conducted for articles in English describing electrophysiological monitoring in ABI from January 1990 to August 2013. A total of 165 studies were included. EEG is a useful monitor for seizure and ischemia detection. There is a well-described role for EEG in convulsive status epilepticus and cardiac arrest (CA). Data suggest EEG should be considered in all patients with ABI and unexplained and persistent altered consciousness and in comatose intensive care unit (ICU) patients without an acute primary brain condition who have an unexplained impairment of mental status. There remain uncertainties about certain technical details, e.g., the minimum duration of EEG studies, the montage, and electrodes. Data obtained from both EEG and EP studies may help estimate prognosis in ABI patients, particularly following CA and traumatic brain injury. Data supporting these recommendations is sparse, and high quality studies are needed. EEG is used to monitor and detect seizures and ischemia in ICU patients and indications for EEG are clear for certain disease states, however, uncertainty remains on other applications. PMID:25208668

  15. Acute Kidney Injury Subsequent to Cardiac Surgery

    PubMed Central

    Kramer, Robert S.; Herron, Crystal R.; Groom, Robert C.; Brown, Jeremiah R.

    2015-01-01

    Abstract: Acute kidney injury (AKI) after cardiac surgery is a common and underappreciated syndrome that is associated with poor short- and long-term outcomes. AKI after cardiac surgery may be epiphenomenon, a signal for adverse outcomes by virtue of other affected organ systems, and a consequence of multiple factors. Subtle increases in serum creatinine (SCr) postoperatively, once considered inconsequential, have been shown to reflect a kidney injury that likely occurred in the operating room during cardiopulmonary bypass (CPB) and more often in susceptible individuals. The postoperative elevation in SCr is a delayed signal reflecting the intraoperative injury. Preoperative checklists and the conduct of CPB represent opportunities for prevention of AKI. Newer definitions of AKI provide us with an opportunity to scrutinize perioperative processes of care and determine strategies to decrease the incidence of AKI subsequent to cardiac surgery. Recognizing and mitigating risk factors preoperatively and optimizing intraoperative practices may, in the aggregate, decrease the incidence of AKI. This review explores the pathophysiology of AKI and addresses the features of patients who are the most vulnerable to AKI. Preoperative strategies are discussed with particular attention to a readiness for surgery checklist. Intraoperative strategies include minimizing hemodilution and maximizing oxygen delivery with specific suggestions regarding fluid management and plasma preservation. PMID:26390675

  16. Acute Kidney Injury Subsequent to Cardiac Surgery.

    PubMed

    Kramer, Robert S; Herron, Crystal R; Groom, Robert C; Brown, Jeremiah R

    2015-03-01

    Acute kidney injury (AKI) after cardiac surgery is a common and underappreciated syndrome that is associated with poor shortand long-term outcomes. AKI after cardiac surgery may be epiphenomenon, a signal for adverse outcomes by virtue of other affected organ systems, and a consequence of multiple factors. Subtle increases in serum creatinine (SCr) postoperatively, once considered inconsequential, have been shown to reflect a kidney injury that likely occurred in the operating room during cardiopulmonary bypass (CPB) and more often in susceptible individuals. The postoperative elevation in SCr is a delayed signal reflecting the intraoperative injury. Preoperative checklists and the conduct of CPB represent opportunities for prevention of AKI. Newer definitions of AKI provide us with an opportunity to scrutinize perioperative processes of care and determine strategies to decrease the incidence of AKI subsequent to cardiac surgery. Recognizing and mitigating risk factors preoperatively and optimizing intraoperative practices may, in the aggregate, decrease the incidence of AKI. This review explores the pathophysiology of AKI and addresses the features of patients who are the most vulnerable to AKI. Preoperative strategies are discussed with particular attention to a readiness for surgery checklist. Intraoperative strategies include minimizing hemodilution and maximizing oxygen delivery with specific suggestions regarding fluid management and plasma preservation. PMID:26390675

  17. [Pre-hospital care management of acute spinal cord injury].

    PubMed

    Hess, Thorsten; Hirschfeld, Sven; Thietje, Roland; Lönnecker, Stefan; Kerner, Thoralf; Stuhr, Markus

    2016-04-01

    Acute injury to the spine and spinal cord can occur both in isolation as also in the context of multiple injuries. Whereas a few decades ago, the cause of paraplegia was almost exclusively traumatic, the ratio of traumatic to non-traumatic causes in Germany is currently almost equivalent. In acute treatment of spinal cord injury, restoration and maintenance of vital functions, selective control of circulation parameters, and avoidance of positioning or transport-related additional damage are in the foreground. This article provides information on the guideline for emergency treatment of patients with acute injury of the spine and spinal cord in the preclinical phase. PMID:27070515

  18. Babesiosis-induced acute kidney injury with prominent urinary macrophages.

    PubMed

    Luciano, Randy L; Moeckel, Gilbert; Palmer, Matthew; Perazella, Mark A

    2013-10-01

    Babesia is an obligate intracellular erythrocyte parasite that can infect humans. Severe symptomatic disease from massive hemolysis and multiorgan system failure, including acute kidney injury (AKI), occurs. Acute tubular injury from a combination of volume depletion and heme pigment toxicity from profound hemolysis is the most common cause of AKI. We present a case of severe babesiosis complicated by dialysis-requiring AKI with the unique finding of large macrophages containing engulfed erythrocyte fragments in urine sediment. This urinary finding raised the possibility of another diagnosis distinct from acute tubular injury. Subsequent kidney biopsy demonstrated infection-associated acute interstitial nephritis. PMID:23643302

  19. Acute vertebrobasilar ischemic stroke due to electric injury.

    PubMed

    Singh Jain, Rajendra; Kumar, Sunil; Suresh, Desai Tushar; Agarwal, Rakesh

    2015-07-01

    Electrical injuries are most commonly due to household accidents.Various factors determine the severity of electric injury, including type of current, amperage, voltage, tissue resistance, pathway of current,and duration of contact with the body. Various types of neurologic damage due to electrical injury have been described in literature. It may manifest as peripheral nerve injury, spinal cord damage, seizures, cerebellarataxia, hypoxic encephalopathy, and intracerebral hemorrhage. Acute ischemic stroke is an infrequent complication of electrical injury. Herein,we report a case of middle-aged man, who accidentally sustained high voltage electrical injury followed by acute vertebrobasilar ischemic stroke. Magnetic resonance imaging of the brain showed acute infarctin bilateral cerebellar and medial occipital regions. Computed tomographic angiogram of the brain and neck vessels was normal. Possibly,in our patient, the mechanism could be related to direct vascular injury due to electric current. PMID:25684743

  20. The effects of sexual assault-related intrusion suppression in the laboratory and natural environment.

    PubMed

    Rosenthal, M Zachary; Follette, Victoria M

    2007-01-01

    Individuals with a history of sexual victimization often experience enduring intrusive thoughts associated with their assault history. Research suggests that the characteristic ways in which sexually assaulted individuals respond to aversive internal experiences (i.e., thoughts, emotions, etc.) can influence the psychological distress associated with these intrusions. This study investigated the effects of suppressing sexual assault-related intrusions in a sample of 61 female college students with a history of adolescent or adult sexual assault and recent assault-related intrusions. Participants were randomly assigned to suppress or monitor intrusions during a laboratory task and for 48 h outside the laboratory. In contrast to study hypotheses, findings indicated that intrusion monitoring was associated with higher subjective distress than suppression both in the laboratory and in the natural environment. No differences were found for the frequency of intrusions between groups in the laboratory. However, modest evidence for a rebound effect in intrusion frequency was found outside the laboratory. PMID:16580627

  1. Acute Kidney Injury Associated with Linagliptin.

    PubMed

    Nandikanti, Deepak K; Gosmanova, Elvira O; Gosmanov, Aidar R

    2016-01-01

    Linagliptin is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that is approved for the treatment of type 2 diabetes mellitus. About 5% of linagliptin is eliminated by the kidneys and no dose adjustment is recommended in kidney impairment. We report a first case of linagliptin-associated acute kidney injury (AKI) in a patient with preexisting chronic kidney disease (CKD). We hypothesize that AKI was due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use, which is known to impair autoregulation and potentiate hypotension-induced AKI. It may be prudent to exert caution and closely monitor kidney function when initiating linagliptin in combination with ACE-inhibitors in CKD patients. PMID:26981294

  2. Contrast Medium-Induced Acute Kidney Injury

    PubMed Central

    Sadat, Umar; Usman, Ammara; Boyle, Jonathan R.; Hayes, Paul D.; Solomon, Richard J.

    2015-01-01

    Contrast medium-induced acute kidney injury (CI-AKI) is a predominant cause of hospital-acquired renal insufficiency. With an increasing number of contrast medium-enhanced radiological procedures being performed in a rapidly increasing ageing population in the Western world, it is imperative that more attention is given to understand the aetiology of CI-AKI to devise novel diagnostic methods and to formulate effective prophylactic and therapeutic regimens to reduce its incidence and its associated morbidity and mortality. This article presents high-yield information on the above-mentioned aspects of CI-AKI, primarily based on results of randomised controlled trials, meta-analyses, systematic reviews and international consensus guidelines. PMID:26195974

  3. Acute Kidney Injury Associated with Linagliptin

    PubMed Central

    Nandikanti, Deepak K.; Gosmanova, Elvira O.; Gosmanov, Aidar R.

    2016-01-01

    Linagliptin is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that is approved for the treatment of type 2 diabetes mellitus. About 5% of linagliptin is eliminated by the kidneys and no dose adjustment is recommended in kidney impairment. We report a first case of linagliptin-associated acute kidney injury (AKI) in a patient with preexisting chronic kidney disease (CKD). We hypothesize that AKI was due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use, which is known to impair autoregulation and potentiate hypotension-induced AKI. It may be prudent to exert caution and closely monitor kidney function when initiating linagliptin in combination with ACE-inhibitors in CKD patients. PMID:26981294

  4. Transfusion-related acute lung injury (TRALI).

    PubMed

    Roberts, George H

    2004-01-01

    Transfusion is an inevitable event in the life of many individuals. Transfusion medicine personnel attempt to provide blood products that will result in a safe and harmless transfusion. However, this is not always possible since no laboratory test gives totally accurate and reliable results all the time and testing in routine transfusion services is devoted primarily to the identification of red blood cell problems. Thus, when patients are transfused, several possible adverse effects may occur in the transfused patient even though quality testing indicates no potential problem. These adverse events include infectious complications, hemolytic reactions, anaphylaxis, urticaria, circulatory overload, transfusion-associated graft-versus-host disease, chills and fever, immunomodulation, and transfusion-related acute lung injury (TRALI). PMID:15314887

  5. Acute kidney injury in HCT: an update.

    PubMed

    Lopes, J A; Jorge, S; Neves, M

    2016-06-01

    Acute kidney injury (AKI) is highly prevalent whether the patients undergo myeloablative or non-myeloablative hematopoietic cell transplantation (HCT); however, the pathogenesis and risk factors leading to AKI can differ between the two. The prognosis of AKI in patients receiving HCT is poor. In fact, AKI following HCT is associated not only with increased short- and long-term mortality, but also with progression to chronic kidney disease. Herein, the authors provide a comprehensive and up-to-date review of the definition and diagnosis, as well as of the incidence, pathogenesis and outcome of AKI in patients undergoing HCT, centering on the differences between myeloablative and non-myeloablative regimens. PMID:26855155

  6. The Anatomic Pattern of Injuries in Acute Inversion Ankle Sprains

    PubMed Central

    Khor, Yuet Peng; Tan, Ken Jin

    2013-01-01

    Background: There are little data on the incidence and patterns of injuries seen on magnetic resonance imaging (MRI) in acute inversion ankle sprains. This study may help in the understanding of the pathomechanics, natural history, and outcomes of this common injury. Study Design: Case series; Level of evidence, 4. Methods: From June 2011 to June 2013, a total of 64 consecutive patients had MRI of the ankle performed for acute inversion injury to the ankle. All injuries/pathologies reported were recorded. Results: Only 22% of patients had isolated lateral ligament complex injuries. Twenty-two percent of patients had other pathologies but no lateral ligament injury, and 53% had lateral ligament injuries in combination with other pathologies or injuries. The most common associated finding with lateral ligament injuries was bone bruising (76%) followed by deltoid ligament injury (50%). The overall incidence of bone bruising was 50%. Thirty percent of ankles had tendon pathology, 27% had deltoid ligament injury, and 22% had occult fractures. Conclusion: Isolated lateral ligament ankle injury is not as common as is believed. The pattern of injury seems complex, and most patients appear to have more injuries than expected. MRI reveals additional information that may have significance in terms of diagnosis, treatment, and prognosis in this common injury. PMID:26535261

  7. Cardiac Surgery-Associated Acute Kidney Injury

    PubMed Central

    Mao, Huijuan; Katz, Nevin; Ariyanon, Wassawon; Blanca-Martos, Lourdes; Adýbelli, Zelal; Giuliani, Anna; Danesi, Tommaso Hinna; Kim, Jeong Chul; Nayak, Akash; Neri, Mauro; Virzi, Grazia Maria; Brocca, Alessandra; Scalzotto, Elisa; Salvador, Loris; Ronco, Claudio

    2013-01-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. PMID:24454314

  8. Septic acute kidney injury: the glomerular arterioles.

    PubMed

    Bellomo, Rinaldo; Wan, Li; Langenberg, Christoph; Ishikawa, Ken; May, Clive N

    2011-01-01

    Acute kidney injury (AKI) is a serious condition that affects many intensive care unit (ICU) patients. The most common causes of AKI in the ICU are severe sepsis and septic shock. The mortality of AKI in septic critically ill patients remains high despite our increasing ability to support vital organs. This is partly due to our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. However, new concepts are emerging to explain the pathogenesis of septic AKI, which challenge previously held dogma. Throughout the past half century, septic AKI has essentially been considered secondary to tubular injury, which, in turn, has been considered secondary to renal ischemia. This belief is curious because the hallmark of septic AKI and AKI in general is the loss of glomerular filtration rate (GFR). It would seem logical, therefore, to focus on the glomerulus in trying to understand why such loss of GFR occurs. Recent experimental observations suggest that, at least in the initial phases of septic AKI, profound changes occur which involve glomerular hemodynamics and lead to loss of GFR. These observations imply that changes in the vasoconstrictor tone of both the afferent and efferent arterioles are an important component of the pathogenesis of septic AKI. PMID:21921614

  9. Sepsis-Associated Acute Kidney Injury

    PubMed Central

    Alobaidi, Rashid; Basu, Rajit K.; Goldstein, Stuart L.; Bagshaw, Sean M.

    2015-01-01

    Summary Acute kidney injury (AKI) is an epidemic problem. Sepsis has long been recognized as a foremost precipitant of AKI. Sepsis-associated AKI (SA-AKI) portends a high burden of morbidity and mortality in both children and adults with critical illness. Although our understanding of its pathophysiology is incomplete, SA-AKI likely represents a distinct subset of AKI contributed to by a unique constellation of hemodynamic, inflammatory, and immune mechanisms. SA-AKI poses significant clinical challenges for clinicians. To date, no singular effective therapy has been developed to alter the natural history of SA-AKI. Rather, current strategies to alleviate poor outcomes focus on clinical risk identification, early detection of injury, modifying clinician behavior to avoid harm, early appropriate antimicrobial therapy, and surveillance among survivors for the longer-term sequelae of kidney damage. Recent evidence has confirmed that patients no longer die with AKI, but from AKI. To improve the care and outcomes for sufferers of SA-AKI, clinicians need a robust appreciation for its epidemiology and current best-evidence strategies for prevention and treatment. PMID:25795495

  10. [Transfusion-related acute lung injury].

    PubMed

    Tank, S; Sputtek, A; Kiefmann, R

    2013-04-01

    Transfusion-related acute lung injury (TRALI) developed into the leading cause of transfusion-related morbidity and mortality after the first description by Popovsky et al. approximately three decades ago. It was the most frequent reason for transfusion-related fatalities worldwide before implementation of risk minimization strategies by donor selection. Plasma-rich blood products, such as fresh frozen plasma and apheresis platelets seem to be the leading triggers of TRALI. Hypoxemia and development of pulmonary edema within 6 h of transfusion are the diagnostic criteria for TRALI. The differentiation between cardiac failure and other transfusion-related lung injuries, such astransfusion-associated circulatory overload ( TACO) is difficult and causal treatment is not available. Therapy is based on supportive measures, such as oxygen insufflationor mechanical ventilation. The exactly pathogenesis is still unknown but the most propagated hypothesis is the two-event-model. Neutrophils are primed by the underlying condition, e.g. sepsis or trauma during the first event and these primed neutrophils are activated by transfused leukoagglutinating antibodies (immunogen) or bioreactive mediators (non-immunogen) during the second-event. Transfusion of leukoagglutinating antibodies from female donors with one or more previous pregnancies is the most frequent reason. No more TRALI fatalities were reported after implementation of the donor selection in Germany in 2009. PMID:23558721

  11. Cardiac surgery-associated acute kidney injury.

    PubMed

    Mao, Huijuan; Katz, Nevin; Ariyanon, Wassawon; Blanca-Martos, Lourdes; Adýbelli, Zelal; Giuliani, Anna; Danesi, Tommaso Hinna; Kim, Jeong Chul; Nayak, Akash; Neri, Mauro; Virzi, Grazia Maria; Brocca, Alessandra; Scalzotto, Elisa; Salvador, Loris; Ronco, Claudio

    2013-10-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. PMID:24454314

  12. Acute renal injury after partial hepatectomy

    PubMed Central

    Peres, Luis Alberto Batista; Bredt, Luis Cesar; Cipriani, Raphael Flavio Fachini

    2016-01-01

    Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs. PMID:27478539

  13. Acute renal injury after partial hepatectomy.

    PubMed

    Peres, Luis Alberto Batista; Bredt, Luis Cesar; Cipriani, Raphael Flavio Fachini

    2016-07-28

    Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs. PMID:27478539

  14. Wasp sting-induced acute kidney injury

    PubMed Central

    Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Sakthirajan, Ramanathan; Shankar, Palaniselvam; Gopalakrishnan, Natarajan; Balasubramaniyan, Thoppalan

    2016-01-01

    Background Wasp stings are a common form of envenomation in tropical countries, especially in farmers. The aim of this study was to document the clinical presentation, treatment and outcomes of patients with acute kidney injury (AKI) due to multiple wasp stings in a tertiary care hospital. Methods We conducted a retrospective observational study of patients with multiple wasp stings and AKI at the Department of Nephrology between July 2011 and August 2015. The clinical features, laboratory data, treatment details and outcomes were noted. Results A total of 11 patients were included. All were from rural areas. All of them were males with age ranging from 21 to 70 years, mean age 45 ± 23 years. Six had oliguria and two had hypotension. All 11 patients had evidence of rhabdomyolysis and three also had hemolysis. Ten patients required hemodialysis with a mean number of hemodialysis sessions of 8.7 ± 2.8. Renal biopsy carried out on four patients, showed acute interstitial nephritis (AIN) in one patient, acute tubular necrosis (ATN) in two patients, and one patient had both AIN and ATN. The two patients with AIN were given steroids, while all other patients were managed with supportive measures. One patient died within 48 h of presentation due to shock. At a mean follow-up of 24 months, one had progressed to chronic kidney disease and the remaining nine had normal renal function. Conclusions Wasp sting is an occupational hazard. AKI was most commonly due to rhabdomyolysis. Early renal biopsy is indicated in those patients who do not respond to supportive measures. Timely dialysis and steroid in the case of AIN improves renal survival. PMID:26985369

  15. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide

    PubMed Central

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  16. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide.

    PubMed

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  17. Acute Kidney Injury: Quoi de Neuf?

    PubMed Central

    Reichel, Ronald R.

    2014-01-01

    Background Acute kidney injury (AKI) is frequently encountered in the nephrology practice. Serum creatinine, with its many shortcomings, is still the main biomarker used to detect AKI. Methods This review focuses on recent advances in definition, diagnosis, risk factors, and molecular mechanisms of AKI. In addition, specific AKI syndromes such as contrast-induced AKI, hepatorenal syndrome, and acute decompensated heart failure are discussed. The connection between AKI and subsequent chronic kidney disease and recent developments in renal replacement therapy are also covered. Results Novel biomarkers such as cystatin C and neutrophil gelatinase–associated lipocalin (NGAL) are being investigated to replace serum creatinine in the detection of AKI. Recent studies suggest that intravenous (IV) fluid use is beneficial for the prevention of contrast-induced AKI, while N-acetylcysteine use is not as well established. Diuretics are clearly beneficial in the treatment of acute decompensated heart failure. Ultrafiltration is less promising and can lead to adverse side effects. Although terlipressin use in hepatorenal syndrome is associated with reduced mortality, it is not available in the United States; combination therapy with midodrine, octreotide, and albumin provides an alternative. Fluid resuscitation is frequently used in critically ill patients with AKI; however, overly aggressive fluid resuscitation is frequently associated with an increased risk of mortality. A 3-step approach that combines guided fluid resuscitation, establishment of an even fluid balance, and an appropriate rate of fluid removal may be beneficial. If fluid resuscitation is needed, crystalloid solutions are preferred over hetastarch solutions. Renal replacement therapy is the last resort in AKI treatment, and timing, modality, and dosing are discussed. Research suggests that AKI leads to an increased incidence of subsequent chronic kidney disease. However, this relationship has not been fully

  18. MicroRNAs in acute kidney injury.

    PubMed

    Fan, Pei-Chun; Chen, Chia-Chun; Chen, Yung-Chang; Chang, Yu-Sun; Chu, Pao-Hsien

    2016-01-01

    Acute kidney injury (AKI) is an important clinical issue that is associated with significant morbidity and mortality. Despite research advances over the past decades, the complex pathophysiology of AKI is not fully understood. The regulatory mechanisms underlying post-AKI repair and fibrosis have not been clarified either. Furthermore, there is no definitively effective treatment for AKI. MicroRNAs (miRNAs) are endogenous single-stranded noncoding RNAs of 19~23 nucleotides that have been shown to be crucial to the post-transcriptional regulation of various cellular biological functions, including proliferation, differentiation, metabolism, and apoptosis. In addition to being fundamental to normal development and physiology, miRNAs also play important roles in various human diseases. In AKI, some miRNAs appear to act pathogenically by promoting inflammation, apoptosis, and fibrosis, while others may act protectively by exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenic effects. Thus, miRNAs have not only emerged as novel biomarkers for AKI; they also hold promise to be potential therapeutic targets. PMID:27608623

  19. Inductive and Deductive Approaches to Acute Cell Injury

    PubMed Central

    DeGracia, Donald J.; Tri Anggraini, Fika; Taha, Doaa Taha Metwally; Huang, Zhi-Feng

    2014-01-01

    Many clinically relevant forms of acute injury, such as stroke, traumatic brain injury, and myocardial infarction, have resisted treatments to prevent cell death following injury. The clinical failures can be linked to the currently used inductive models based on biological specifics of the injury system. Here we contrast the application of inductive and deductive models of acute cell injury. Using brain ischemia as a case study, we discuss limitations in inductive inferences, including the inability to unambiguously assign cell death causality and the lack of a systematic quantitative framework. These limitations follow from an overemphasis on qualitative molecular pathways specific to the injured system. Our recently developed nonlinear dynamical theory of cell injury provides a generic, systematic approach to cell injury in which attractor states and system parameters are used to quantitatively characterize acute injury systems. The theoretical, empirical, and therapeutic implications of shifting to a deductive framework are discussed. We illustrate how a deductive mathematical framework offers tangible advantages over qualitative inductive models for the development of therapeutics of acutely injured biological systems. PMID:27437490

  20. [PARTICULAR QUALITIES OF DIAGNOSTIC ACUTE LATERAL ANKLE LIGAMENT INJURIES].

    PubMed

    Krasnoperov, S N; Shishka, I V; Golovaha, M L

    2015-01-01

    Delayed diagnosis of acute lateral ankle ligaments injury and subsequent inadequate treatment leads to the development of chronic instability and rapid progression of degenerative processes in the joint. The aim of our work was to improve treatment results by developing an diagnostic algorithm and treatment strategy of acute lateral ankle ligament injuries. The study included 48 patients with history of acute inversion ankle injury mechanism. Diagnostic protocol included clinical and radiological examination during 48 hours and after 7-10 days after injury. According to the high rate of inaccurate clinical diagnosis in the first 48 hours of the injury a short course of conservative treatment for 7-10 days is needed with follow-up and controlling clinical and radiographic instability tests. Clinical symptoms of ankle inversion injury showed that the combination of local tenderness in the projection of damaged ligaments, the presence of severe periarticular hematoma in the lateral department and positive anterior drawer and talar tilt tests in 7-10 days after the injury in 87% of cases shows the presence of ligament rupture. An algorithm for diagnosis of acute lateral ankle ligament injury was developed, which allowed us to determine differential indications for surgical repair of the ligaments and conservative treatment of these patients. PMID:27089717

  1. MRI in acute ligamentous injuries of the ankle.

    PubMed

    Martella, Ilenia; Azzali, Emanuele; Milanese, Gianluca; Praticò, Francesco Emanuele; Ruggirello, Margherita; Trunfio, Vincenzo; Parziale, Raffaele; Corrado, Michele; Della Casa, Giovanni; Capasso, Raffaella; De Filippo, Massimo

    2016-01-01

    Ankle sprains are the most common lower limb injuries and affect more frequently young athletes; imaging is needed for an accurate diagnosis of such traumatic injuries. The purpose of this review is to analyse the magnetic resonance (MR) findings of both normal and pathological ankle's ligaments; indeed, MRI is the gold standard for the diagnosis of acute traumatic injuries and is useful for differentiation of the causes of ankle instability as well as for pre-operative planning. PMID:27467862

  2. Unique aspects of downhill ski injuries part 2: diagnosis and acute management of specific injuries.

    PubMed

    Buck, P G; Sophocles, A M; Beckenbaugh, R D

    1982-04-01

    As in many sports, a wide spectrum of injuries is seen in skiing (Table 1). This includes injuries to the upper and lower extremities as well as miscellaneous injuries and medical problems (frostbite, hypothermia, and high altitude effects). Six relatively unique injuries in skiing will be presented in detail. The discussion will focus on the acute management of these injuries: subluxing peroneal tendons, fibular stress fractures, tibial shaft fractures (spiral, transverse), medical compartment knee injuries, anterior shoulder dislocations with associated greater tuberosity fractures, and gamekeeper's thumb. PMID:24822536

  3. Acute traumatic injuries in automotive manufacturing.

    PubMed

    Warner, M; Baker, S P; Li, G; Smith, G S

    1998-10-01

    Motor vehicle manufacturing, with its varied tasks, challenging work environment, and diverse worker populations, presents many hazards to employees. This study examined routinely collected surveillance data from a major motor vehicle manufacturer to identify injury types, high-risk workers, causes of injury, and factors associated with work loss. Injury and personnel data were used to calculate injury rates. Injury data were from the routinely collected medical and safety surveillance system on occupational injuries. The number of persons working in the plants was estimated using year-end personnel reports. Key word searches supplementing the analyses provided insight into the specific circumstances of injury. The most common injuries were sprains/strains (39% of the total), lacerations (22%), and contusions (15%). Forty-nine percent of the injuries resulted in one or more lost or restricted workdays; 25% resulted in 7 or more lost or restricted workdays. The injuries most likely to result in work loss were amputations, hernias and fractures. Sprains/strains accounted for 65% of all lost workdays. Injury rates ranged from 13.8 per 100 person-years at stamping plants to 28.7 at parts depots. Even within similar types of plants, injury rates varied widely, with a twofold difference among the individual assembly plants in overall injury rates. Injury surveillance systems with descriptive data on injury events shed light on the circumstances under which certain types of injuries occur and can provide the basis for preventive interventions. Sources of variation and potential biases are discussed, providing guidance for those interested in designing and using surveillance systems for occupational injuries. PMID:9750941

  4. Pediatric traumatic brain injury: acute and rehabilitation costs.

    PubMed

    Jaffe, K M; Massagli, T L; Martin, K M; Rivara, J B; Fay, G C; Polissar, N L

    1993-07-01

    Pediatric traumatic brain injury constitutes an enormous public health problem, but little is known about the economic costs of such injury. Using charges as a proxy for cost, we prospectively collected data on initial hospital charges and professional fees for emergency department services, acute inpatient care, and acute inpatient rehabilitation for 96 patients with mild, moderate, and severe traumatic brain injuries. We also examined the relationship between these costs and injury severity and etiology. Acute care and rehabilitation median costs were $5,233 per child, $11,478 for hospitalized children, and $230 for those only seen in the emergency department. Median costs for injuries due to motor vehicles, bicycles, and falls were $15,213, $6,311, and $792, respectively. Using Glasgow Coma Scale criteria, median cost of mild, moderate, and severe traumatic brain injuries were $598, $12,022, and $53,332, respectively. Injury etiology added modestly but significantly to the prediction of cost over and above that predicted by injury severity alone. Rehabilitation costs accounted for 37% of the total for all children, but 45% of those with the most severe injuries. PMID:8328886

  5. Recent advances in the understanding of acute kidney injury

    PubMed Central

    Tögel, Florian

    2014-01-01

    Acute kidney injury (AKI) is a common clinical entity associated with high morbidity and mortality and clinical costs. The pathophysiology is multifaceted and involves inflammation, tubular injury, and vascular damage. Recently identified components include necroptosis, a special form of cell death, and autophagy. Most of the pathophysiological knowledge is obtained from animal models but these do not directly reflect the reality of the clinical situation. Tubular cells have a remarkable capacity to regenerate, and the role of stem/progenitor cells is discussed. Acute kidney injury is frequently associated with chronic kidney disease, and the implications are widespread. PMID:25343040

  6. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

    NASA Astrophysics Data System (ADS)

    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  7. Molecular determinants of acute kidney injury

    PubMed Central

    Husi, Holger; Human, Christin

    2015-01-01

    Abstract: Background: Acute kidney injury (AKI) is a condition that leads to a rapid deterioration of renal function associated with impairment to maintain electrolyte and acid balance, and, if left untreated, ultimately irreversible kidney damage and renal necrosis. There are a number of causes that can trigger AKI, ranging from underlying conditions as well as trauma and surgery. Specifically, the global rise in surgical procedures led to a substantial increase of AKI incidence rates, which in turn impacts on mortality rates, quality of life and economic costs to the healthcare system. However, no effective therapy for AKI exists. Current approaches, such as pharmacological intervention, help in alleviating symptoms in slowing down the progression, but do not prevent or reverse AKI-induced organ damage. Methods: An in-depth understanding of the molecular machinery involved in and modulated by AKI induction and progression is necessary to specifically pharmacologically target key molecules. A major hurdle to devise a successful strategy is the multifactorial and complex nature of the disorder itself, whereby the activation of a number of seemingly independent molecular pathways in the kidney leads to apoptotic and necrotic events. Results: The renin-angiotensin-aldosterone-system (RAAS) axis appears to be a common element, leading to downstream events such as triggers of immune responses via the NFB pathway. Other pathways intricately linked with AKI-induction and progression are the tumor necrosis factor alpha (TNF α) and transforming growth factor beta (TGF β) signaling cascades, as well as a number of other modulators. Surprisingly, it has been shown that the involvement of the glutamatergic axis, believed to be mainly a component of the neurological system, is also a major contributor. Conclusions: Here we address the current understanding of the molecular pathways evoked in AKI, their interplay, and the potential to pharmacologically intervene in the

  8. Molecular mediators of favism-induced acute kidney injury.

    PubMed

    García-Camín, Rosa María; Goma, Montserrat; Osuna, Rosa García; Rubio-Navarro, Alfonso; Buendía, Irene; Ortiz, Alberto; Egido, Jesús; Manzarbeitia, Félix; Chevarria, Julio Leonel; Gluksmann, María Constanza; Moreno, Juan Antonio

    2014-03-01

    Intolerance to fava beans in subjects with glucose-6-phosphate-dehydrogenase deficiency (favism) may lead to severe hemolytic crises and decreased renal function. Renal biopsy findings exploring the molecular mechanisms of renal damage in favism have not been previously reported. We report a case of favism-associated acute kidney injury in which renal biopsy showed acute tubular necrosis and massive iron deposits in tubular cells. Interestingly, iron deposit areas were characterized by the presence of oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) and macrophages expressing the hemoglobin scavenger receptor CD163. In addition, iron deposits, NADPH-p22 phox, hemeoxigenase- 1 and CD163 positive cells were observed in some glomeruli. These results identify both glomerular and tubular involvement in favism-associated acute kidney injury and suggest novel therapeutic targets to prevent or accelerate recovery from acute kidney injury. PMID:23006341

  9. The incidence of acute hospital-treated eye injuries.

    PubMed

    Karlson, T A; Klein, B E

    1986-10-01

    Little information is available on the incidence and severity of eye injuries despite the disfigurement and vision loss they cause. From a population-based study in Dane County, Wisconsin, the incidence of acute hospital-treated eye injuries was 423/100,000 residents in 1979. The most common causes of eye injuries were assaults, work-related events, sports and recreational activities, motor vehicle crashes, and falls. Consumer products were involved in almost 70% (9/13) of severe eye injuries classified as severe. Injuries from fireworks were not found at all in this population. Implementing known strategies for eye injury prevention would substantially reduce their incidence. These include requiring certified eye protectors at workplaces and in sports activities whenever possible rather than making their use voluntary. For the preponderance of eye injuries, however, modifying potentially hazardous consumer products, including the interior of passenger cars, will be necessary. PMID:3767676

  10. Endovascular Treatment of Acute and Chronic Thoracic Aortic Injury

    SciTech Connect

    Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan

    2007-11-15

    Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.

  11. Acute Kidney Injury is More Common in Acute Haemorrhagic Stroke in Mymensingh Medical College Hospital.

    PubMed

    Ray, N C; Chowdhury, M A; Sarkar, S R

    2016-01-01

    Acute kidney injury (AKI) is a common complication after acute stroke and is an independent predictor of both early and long-term mortality after acute stroke. Acute kidney injury is associated with increased mortality in haemorrhagic stroke patients. This cross sectional observational study was conducted in Nephrology, Neuromedicine and Medicine department of Mymensingh Medical College & Hospital, Mymensingh from July 2012 to June 2014. A total of 240 patients with newly detected acute stroke confirmed by CT scan of brain were included in this study. According to this study, 15.42% of acute stroke patients developed AKI. Among the patients with haemorrhagic stroke 21.87% developed AKI while only 13.07% patients with ischaemic stroke developed AKI. So, early diagnosis and management of AKI in patients with acute stroke especially in haemorrhagic stroke is very important to reduce the morbidity and mortality of these patients. PMID:26931240

  12. Acute blast injury reduces brain abeta in two rodent species.

    PubMed

    De Gasperi, Rita; Gama Sosa, Miguel A; Kim, Soong Ho; Steele, John W; Shaughness, Michael C; Maudlin-Jeronimo, Eric; Hall, Aaron A; Dekosky, Steven T; McCarron, Richard M; Nambiar, Madhusoodana P; Gandy, Sam; Ahlers, Stephen T; Elder, Gregory A

    2012-01-01

    Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). The β-amyloid (Aβ) peptide associated with the development of Alzheimer's disease is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain Aβ following experimental blast injury using enzyme-linked immunosorbent assays for Aβ 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain Aβ levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP) were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the β-secretase, β-site APP cleaving enzyme 1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain. PMID:23267342

  13. [Acute and overuse injuries in elite paracycling - an epidemiological study].

    PubMed

    Kromer, P; Röcker, K; Sommer, A; Baur, H; Konstantinidis, L; Gollhofer, A; Südkamp, N P; Hirschmüller, A

    2011-09-01

    Although paracycling is a growing discipline in high level competitive sports as well as in posttraumatic rehabilitation, epidemiological data of resulting injuries is still missing. Therefore, 19 athletes of the German national paracycling team were asked about their injuries during the 2008 season using a standardized questionnaire. Overall, 18 (94.7 %) of 19 athletes reported overuse injuries; most commonly localized at the back (83.3 %), neck/shoulder (77.8 %), knee (50 %), groin/buttock (50 %) and hands/wrists (38.9 %). Altogether, 18 accidents were registered, corresponding to an injury rate of 0,95 acute injuries per athlete per year (0,07 / 1000 km). The most common acute injuries were abrasions (69.2 %) and contusions (61.5 %), whereas fractures were stated only twice (11.8 %). The anatomical distribution of overuse injuries in disabled cyclists confirms the results of studies in able-bodied cycling, although the incidences in low-back pain and neck/shoulder pain is clearly higher in disabled cycling, as well as the rate of traumatic injuries. PMID:21922439

  14. Acute assessment and management of burn injuries.

    PubMed

    Purdue, Gary F; Arnoldo, Brett D; Hunt, John L

    2011-05-01

    Burns are ubiquitous injuries in modern society, with virtually all adults having sustained a burn at some point in their lives. The skin is the largest organ of the body, basically functioning to protect self from non-self. Burn injury to the skin is painful, resource-intensive, and often associated with scarring, contracture formation, and long-term disability. Larger burns are associated with morbidity and mortality disproportionate to their initial appearance. Electrical and chemical burns are less common injuries but are often associated with significant morbidity. PMID:21624716

  15. Acute aortic dissection from cross-clamp injury.

    PubMed

    Litchford, B; Okies, J E; Sugimura, S; Starr, A

    1976-11-01

    Acute dissection of the ascending aorta secondary to cross-clamp injury can be successfully managed if the problem is recognized immediately. Bypass must be instituted after recannulation at a point distal to the innominate artery so that proper exposure of the site of injury can be obtained. Systemic as well as local hypothermia for myocardial preservation are both necessary. Direct suture closure of all layers at the site of dissection over Teflon felt can terminate this process. PMID:979312

  16. Ammonium dichromate poisoning: A rare cause of acute kidney injury

    PubMed Central

    Radhakrishnan, H.; Gopi, M.; Arumugam, A.

    2014-01-01

    Ammonium dichromate is an inorganic compound frequently used in screen and color printing. Being a strong oxidizing agent, it causes oxygen free radical injury resulting in organ failure. We report a 25-year-old female who presented with acute kidney injury after consumption of ammonium dichromate. She was managed successfully with hemodialysis and supportive measures. This case is reported to highlight the toxicity of ammonium dichromate. PMID:25484533

  17. Acute Management of Nutritional Demands after Spinal Cord Injury

    PubMed Central

    Thibault-Halman, Ginette; Casha, Steven; Singer, Shirley

    2011-01-01

    Abstract A systematic review of the literature was performed to address pertinent clinical questions regarding nutritional management in the setting of acute spinal cord injury (SCI). Specific metabolic challenges are present following spinal cord injury. The acute stage is characterized by a reduction in metabolic activity, as well as a negative nitrogen balance that cannot be corrected, even with aggressive nutritional support. Metabolic demands need to be accurately monitored to avoid overfeeding. Enteral feeding is the optimal route following SCI. When oral feeding is not possible, nasogastric, followed by nasojejunal, then by percutaneous endoscopic gastrostomy, if necessary, is suggested. PMID:20373845

  18. Severe but reversible acute kidney injury resulting from Amanita punctata poisoning

    PubMed Central

    Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee

    2015-01-01

    Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney injury. PMID:26779427

  19. Dyselectrolytemia in acute kidney injury causing tetany and quadriparesis.

    PubMed

    Palkar, Atul Vijay; Mewada, Mayur; Thakur, Sonal; Shrivastava, Makardhwaj Sarvadaman

    2011-01-01

    A 40-year-old female, presented with prerenal acute kidney injury secondary to diarrhoea. With appropriate hydration, she went into diuretic phase and subsequently developed hypokalemic quadriparesis with hypocalcaemic tetany due to hypomagnesemia and subclinical vitamin D deficiency. The patient improved with oral potassium, magnesium, calcium and vitamin D supplementation. PMID:22674589

  20. Acute kidney injury and dermonecrosis after Loxosceles reclusa envenomation

    PubMed Central

    Nag, A.; Datta, J.; Das, A.; Agarwal, A. K.; Sinha, D.; Mondal, S.; Ete, T.; Chakraborty, A.; Ghosh, S.

    2014-01-01

    Spiders of the Loxosceles species can cause dermonecrosis and acute kidney injury (AKI). Hemolysis, rhabdomyolysis and direct toxin-mediated renal damage have been postulated. There are very few reports of Loxoscelism from India. We report a case of AKI, hemolysis and a “gravitational” pattern of ulceration following the bite of the brown recluse spider (Loxosceles spp). PMID:25097339

  1. Acute kidney injury and dermonecrosis after Loxosceles reclusa envenomation.

    PubMed

    Nag, A; Datta, J; Das, A; Agarwal, A K; Sinha, D; Mondal, S; Ete, T; Chakraborty, A; Ghosh, S

    2014-07-01

    Spiders of the Loxosceles species can cause dermonecrosis and acute kidney injury (AKI). Hemolysis, rhabdomyolysis and direct toxin-mediated renal damage have been postulated. There are very few reports of Loxoscelism from India. We report a case of AKI, hemolysis and a "gravitational" pattern of ulceration following the bite of the brown recluse spider (Loxosceles spp). PMID:25097339

  2. Pancreatitis-induced acute lung injury. An ARDS model.

    PubMed Central

    Guice, K S; Oldham, K T; Johnson, K J; Kunkel, R G; Morganroth, M L; Ward, P A

    1988-01-01

    Cerulein-induced acute pancreatitis in rats is associated with acute lung injury characterized by increased pulmonary microvascular permeability, increased wet lung weights, and histologic features of alveolar capillary endothelial cell and pulmonary parenchymal injury. The alveolar capillary permeability index is increased 1.8-fold after a 3-hour injury (0.30 to 0.54, p less than 0.05). Gravimetric analysis shows a similar 1.5-fold increase in wet lung weights at 3 hours (0.35% vs. 0.51% of total body weight, p less than 0.05). Histologic features assessed by quantitative morphometric analysis include significant intra-alveolar hemorrhage (0.57 +/- 0.08 vs. 0.12 +/- 0.02 RBC/alveolus at 6 hours, p less than 0.001); endothelial cell disruption (28.11% vs. 4.3%, p less than 0.001); and marked, early neutrophil infiltration (7.45 +/- 0.53 vs. 0.83 +/- 0.18 PMN/hpf at 3 hours, p less than 0.001). The cerulein peptide itself, a cholecystokinin (CCK) analog, is naturally occurring and is not toxic and in several in vitro settings including exposure to pulmonary artery endothelial cells, Type II epithelial cells, and an ex vivo perfused lung preparation. The occurrence of this ARDS-like acute lung injury with acute pancreatitis provides an excellent experimental model to investigate mechanisms and mediators involved in the pathogenesis of ARDS. Images Fig. 1. PMID:3389946

  3. Pancreatitis-induced acute lung injury. An ARDS model.

    PubMed

    Guice, K S; Oldham, K T; Johnson, K J; Kunkel, R G; Morganroth, M L; Ward, P A

    1988-07-01

    Cerulein-induced acute pancreatitis in rats is associated with acute lung injury characterized by increased pulmonary microvascular permeability, increased wet lung weights, and histologic features of alveolar capillary endothelial cell and pulmonary parenchymal injury. The alveolar capillary permeability index is increased 1.8-fold after a 3-hour injury (0.30 to 0.54, p less than 0.05). Gravimetric analysis shows a similar 1.5-fold increase in wet lung weights at 3 hours (0.35% vs. 0.51% of total body weight, p less than 0.05). Histologic features assessed by quantitative morphometric analysis include significant intra-alveolar hemorrhage (0.57 +/- 0.08 vs. 0.12 +/- 0.02 RBC/alveolus at 6 hours, p less than 0.001); endothelial cell disruption (28.11% vs. 4.3%, p less than 0.001); and marked, early neutrophil infiltration (7.45 +/- 0.53 vs. 0.83 +/- 0.18 PMN/hpf at 3 hours, p less than 0.001). The cerulein peptide itself, a cholecystokinin (CCK) analog, is naturally occurring and is not toxic and in several in vitro settings including exposure to pulmonary artery endothelial cells, Type II epithelial cells, and an ex vivo perfused lung preparation. The occurrence of this ARDS-like acute lung injury with acute pancreatitis provides an excellent experimental model to investigate mechanisms and mediators involved in the pathogenesis of ARDS. PMID:3389946

  4. Critical care in the emergency department: acute kidney injury.

    PubMed

    Nee, Patrick A; Bailey, David J; Todd, Victoria; Lewington, Andrew J; Wootten, Andrea E; Sim, Kevin J

    2016-05-01

    Acute kidney injury (AKI) is common among emergency department patients admitted to hospital. There is evidence of inadequate management of the condition leading to adverse outcomes. We present an illustrative case of AKI complicating a gastrointestinal disorder in an older adult. We discuss the clinical presentation, assessment and management of AKI with reference to recent consensus guidelines on classification and treatment. PMID:25969433

  5. Research Progress on Regulatory T Cells in Acute Kidney Injury

    PubMed Central

    Wang, Yamei; Tao, Yuhong

    2015-01-01

    Immune inflammation is crucial in mediating acute kidney injury (AKI). Immune cells of both the innate and adaptive immune systems substantially contribute to overall renal damage in AKI. Regulatory T cells (Tregs) are key regulator of immunological function and have been demonstrated to ameliorate injury in several murine experimental models of renal inflammation. Recent studies have illuminated the renal-protective function of Tregs in AKI. Tregs appear to exert beneficial effects in both the acute injury phase and the recovery phase of AKI. Additionally, Tregs-based immunotherapy may represent a promising approach to ameliorate AKI and promote recovery from AKI. This review will highlight the recent insights into the role of Tregs and their therapeutic potential in AKI. PMID:26273681

  6. Transfusion-Related Acute Lung Injury: The Work of DAMPs*

    PubMed Central

    Land, Walter G.

    2013-01-01

    Current notions in immunology hold that not only pathogen-mediated tissue injury but any injury activates the innate immune system. In principle, this evolutionarily highly conserved, rapid first-line defense system responds to pathogen-induced injury with the creation of infectious inflammation, and non-pathogen-induced tissue injury with ‘sterile’ tissue inflammation. In this review, evidence has been collected in support of the notion that the transfusion-related acute lung injury induces a ‘sterile’ inflammation in the lung of transfused patients in terms of an acute innate inflammatory disease. The inflammatory response is mediated by the patient's innate immune cells including lung-passing neutrophils and pulmonary endothelial cells, which are equipped with pattern recognition receptors. These receptors are able to sense injury-induced, damage-associated molecular patterns (DAMPs) generated during collection, processing, and storage of blood/blood components. The recognition process leads to activation of these innate cells. A critical role for a protein complex known as the NLRP3 inflammasome has been suggested to be at the center of such a scenario. This complex undergoes an initial ‘priming’ step mediated by 1 class of DAMPs and then an ‘activating’ step mediated by another class of DAMPs to activate interleukin-1beta and interleukin-18. These 2 cytokines then promote, via transactivation, the formation of lung inflammation. PMID:23637644

  7. Racial and Ethnic Disparities in Mortality from Acute Lung Injury

    PubMed Central

    Erickson, Sara E.; Shlipak, Michael G.; Martin, Greg S.; Wheeler, Arthur P.; Ancukiewicz, Marek; Matthay, Michael A.; Eisner, Mark D.

    2009-01-01

    Objective: Little is known about the influence of race and ethnicity on mortality from acute lung injury. We sought to determine whether black race or Hispanic ethnicity are independently associated with mortality among patients with acute lung injury. Design: Retrospective cohort study of patients enrolled in the Acute Respiratory Distress Syndrome (ARDS) Network randomized controlled trials. Setting: Adult intensive care units participating in the ARDS Network trials. Patients: 2362 mechanically ventilated patients (1,715 white, 449 black and 198 Hispanic) with acute lung injury. Measurements and Main Results: The primary outcome was 60-day mortality. A secondary outcome was number of ventilator-free days. Crude mortality was 33% for both blacks and Hispanics compared with 27% for whites (p=0.02). After adjusting for demographic and clinical covariates, the association between race/ethnicity and mortality persisted (OR = 1.42; 95% CI 1.10-1.84 for blacks; OR=1.94; 95% CI, 1.36-2.77 for Hispanics; OR=1 for whites, reference). After adjustment for severity of illness (Acute Physiology Score), black race was no longer significantly associated with mortality (OR =1.25; 95% CI, 0.95-1.66), whereas the association with Hispanic ethnicity persisted (OR=2.00; 95% CI, 1.37-2.90). Hispanics had significantly fewer ventilator-free days compared with whites after adjustment for demographic and clinical covariates (mean difference in days = -2.3; 95% CI -3.9 to -0.7). Conclusions: Black and Hispanic patients with acute lung injury have a significantly higher risk of death compared to white patients. This increased risk appeared to be mediated by increased severity of illness at presentation for blacks, but was unexplained among Hispanics. PMID:19050621

  8. Incidence of acute volleyball injuries: a prospective cohort study of injury mechanisms and risk factors.

    PubMed

    Bahr, R; Bahr, I A

    1997-06-01

    The purpose of the study was to examine the incidence and mechanisms of acute volleyball injuries, with particular reference to possible risk factors for ankle injuries. Coaches and players in the top two divisions of the Norwegian Volleyball Federation were asked to keep records of exposure time and all acute volleyball injuries causing a player to miss at least one playing day during one season. We found 89 injuries among 272 players during 51588 player hours, 45837 h of training and 5751 h of match play. The total injury incidence was 1.7 +/- 0.2 per 1000 h of play, 1.5 +/- 0.2 during training and 3.5 +/- 0.8 during match play. The ankle (54%) was the most commonly injured region, followed by the lower back (11%), knee (8%), shoulder (8%) and fingers (7%). Of the ankle injuries, 79% were recurrences, and the relative risk of injury was 3.8 (P < 0.0001) for previously injured ankles (38 of 232) vs. non-injured ankles (10 of the 234). Moreover, a reinjury was observed in 21 of the 50 ankles that had suffered an ankle sprain within the last 6 months (42.0 +/- 7.0%; risk ratio: 9.8 vs. uninjured ankles; P < 0.000001). The data indicate that external supports should be worn for 6-12 months after an ankle sprain and that specific injury prevention programs may be developed for ankle sprains in volleyball. PMID:9200321

  9. Understanding acute ankle ligamentous sprain injury in sports

    PubMed Central

    Fong, Daniel TP; Chan, Yue-Yan; Mok, Kam-Ming; Yung, Patrick SH; Chan, Kai-Ming

    2009-01-01

    This paper summarizes the current understanding on acute ankle sprain injury, which is the most common acute sport trauma, accounting for about 14% of all sport-related injuries. Among, 80% are ligamentous sprains caused by explosive inversion or supination. The injury motion often happens at the subtalar joint and tears the anterior talofibular ligament (ATFL) which possesses the lowest ultimate load among the lateral ligaments at the ankle. For extrinsic risk factors to ankle sprain injury, prescribing orthosis decreases the risk while increased exercise intensity in soccer raises the risk. For intrinsic factors, a foot size with increased width, an increased ankle eversion to inversion strength, plantarflexion strength and ratio between dorsiflexion and plantarflexion strength, and limb dominance could increase the ankle sprain injury risk. Players with a previous sprain history, players wearing shoes with air cells, players who do not stretch before exercising, players with inferior single leg balance, and overweight players are 4.9, 4.3, 2.6, 2.4 and 3.9 times more likely to sustain an ankle sprain injury. The aetiology of most ankle sprain injuries is incorrect foot positioning at landing – a medially-deviated vertical ground reaction force causes an explosive supination or inversion moment at the subtalar joint in a short time (about 50 ms). Another aetiology is the delayed reaction time of the peroneal muscles at the lateral aspect of the ankle (60–90 ms). The failure supination or inversion torque is about 41–45 Nm to cause ligamentous rupture in simulated spraining tests on cadaver. A previous case report revealed that the ankle joint reached 48 degrees inversion and 10 degrees internal rotation during an accidental grade I ankle ligamentous sprain injury during a dynamic cutting trial in laboratory. Diagnosis techniques and grading systems vary, but the management of ankle ligamentous sprain injury is mainly conservative. Immobilization should not

  10. Acute care management of spinal cord injuries.

    PubMed

    Mitcho, K; Yanko, J R

    1999-08-01

    Meeting the health care needs of the spinal cord-injured patient is an immense challenge for the acute care multidisciplinary team. The critical care nurse clinician, as well as other members of the team, needs to maintain a comprehensive knowledge base to provide the care management that is essential to the care of the spinal cord-injured patient. With the active participation of the patient and family in care delivery decisions, the health care professionals can help to meet the psychosocial and physical needs of the patient/family unit. This article provides an evidence-based, comprehensive review of the needs of the spinal cord-injured patient in the acute care setting including optimal patient outcomes, methods to prevent complications, and a plan that provides an expeditious transition to rehabilitation. PMID:10646444

  11. MicroRNAs: Novel regulatory molecules in acute lung injury/acute respiratory distress syndrome

    PubMed Central

    CAO, YONGMEI; LYU, YI; TANG, JIAHUA; LI, YINGCHUAN

    2016-01-01

    Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are common and complex inflammatory lung diseases. MicroRNAs (miRNAs), a type of non-coding RNA molecule that regulate gene expression at the post-transcriptional level, have emerged as a novel class of gene regulators, which have critical roles in a wide range of human disorders and diseases, including ALI. Certain types of miRNAs are abnormally expressed in response to lung injury. miRNAs can regulate inflammation pathways by targeting specific molecules and modulate immune response in the process of lung injury and repair. The regulation of miRNA can relieve injury response and promote the recovery of ALI/ARDS. Therefore, miRNAs may serve as novel therapeutic targets in ALI/ARDS. PMID:27123242

  12. Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

    PubMed Central

    Koeppen, Michael; Eckle, Tobias; Eltzschig, Holger K.

    2011-01-01

    Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion. PMID:21587159

  13. KIM-1-mediated phagocytosis reduces acute injury to the kidney.

    PubMed

    Yang, Li; Brooks, Craig R; Xiao, Sheng; Sabbisetti, Venkata; Yeung, Melissa Y; Hsiao, Li-Li; Ichimura, Takaharu; Kuchroo, Vijay; Bonventre, Joseph V

    2015-04-01

    Kidney injury molecule 1 (KIM-1, also known as TIM-1) is markedly upregulated in the proximal tubule after injury and is maladaptive when chronically expressed. Here, we determined that early in the injury process, however, KIM-1 expression is antiinflammatory due to its mediation of phagocytic processes in tubule cells. Using various models of acute kidney injury (AKI) and mice expressing mutant forms of KIM-1, we demonstrated a mucin domain-dependent protective effect of epithelial KIM-1 expression that involves downregulation of innate immunity. Deletion of the mucin domain markedly impaired KIM-1-mediated phagocytic function, resulting in increased proinflammatory cytokine production, decreased antiinflammatory growth factor secretion by proximal epithelial cells, and a subsequent increase in tissue macrophages. Mice expressing KIM-1Δmucin had greater functional impairment, inflammatory responses, and mortality in response to ischemia- and cisplatin-induced AKI. Compared with primary renal proximal tubule cells isolated from KIM-1Δmucin mice, those from WT mice had reduced proinflammatory cytokine secretion and impaired macrophage activation. The antiinflammatory effect of KIM-1 expression was due to the interaction of KIM-1 with p85 and subsequent PI3K-dependent downmodulation of NF-κB. Hence, KIM-1-mediated epithelial cell phagocytosis of apoptotic cells protects the kidney after acute injury by downregulating innate immunity and inflammation. PMID:25751064

  14. Demographics of acute admissions to a National Spinal Injuries Unit

    PubMed Central

    Boran, S.; Street, J.; Higgins, T.; McCormack, D.; Poynton, A. R.

    2009-01-01

    This prospective demographic study was undertaken to review the epidemiology and demographics of all acute admissions to the National Spinal Injuries Unit in Ireland for the 5 years to 2003. The study was conducted at the National Spinal Injuries Unit, Mater Miscericordiae University Hospital, Dublin, Ireland. Records of all patients admitted to our unit from 1999 to 2003 were compiled from a prospective computerized spinal database. In this 5-year period, 942 patients were acutely hospitalized at the National Spinal Injuries Unit. There were 686 (73%) males and 256 (27%) females, with an average age of 32 years (range 16–84 years). The leading cause of admission with a spinal injury was road traffic accidents (42%), followed by falls (35%), sport (11%), neoplasia (7.5%) and miscellaneous (4.5%). The cervical spine was most commonly affected (51%), followed by lumbar (28%) and thoracic (21%). On admission 38% of patients were ASIA D or worse, of which one-third were AISA A. Understanding of the demographics of spinal column injuries in unique populations can help us to develop preventative and treatment strategies at both national and international levels. PMID:19283414

  15. Utilization and cost of a new model of care for managing acute knee injuries: the Calgary acute knee injury clinic

    PubMed Central

    2012-01-01

    Background Musculoskeletal disorders (MSDs) affect a large proportion of the Canadian population and present a huge problem that continues to strain primary healthcare resources. Currently, the Canadian healthcare system depicts a clinical care pathway for MSDs that is inefficient and ineffective. Therefore, a new inter-disciplinary team-based model of care for managing acute knee injuries was developed in Calgary, Alberta, Canada: the Calgary Acute Knee Injury Clinic (C-AKIC). The goal of this paper is to evaluate and report on the appropriateness, efficiency, and effectiveness of the C-AKIC through healthcare utilization and costs associated with acute knee injuries. Methods This quasi-experimental study measured and evaluated cost and utilization associated with specific healthcare services for patients presenting with acute knee injuries. The goal was to compare patients receiving care from two clinical care pathways: the existing pathway (i.e. comparison group) and a new model, the C-AKIC (i.e. experimental group). This was accomplished through the use of a Healthcare Access and Patient Satisfaction Questionnaire (HAPSQ). Results Data from 138 questionnaires were analyzed in the experimental group and 136 in the comparison group. A post-hoc analysis determined that both groups were statistically similar in socio-demographic characteristics. With respect to utilization, patients receiving care through the C-AKIC used significantly less resources. Overall, patients receiving care through the C-AKIC incurred 37% of the cost of patients with knee injuries in the comparison group and significantly incurred less costs when compared to the comparison group. The total aggregate average cost for the C-AKIC group was $2,549.59 compared to $6,954.33 for the comparison group (p <.001). Conclusions The Calgary Acute Knee Injury Clinic was able to manage and treat knee injured patients for less cost than the existing state of healthcare delivery. The combined results from

  16. Paeoniflorin ameliorates acute necrotizing pancreatitis and pancreatitis‑induced acute renal injury.

    PubMed

    Wang, Peng; Wang, Weixing; Shi, Qiao; Zhao, Liang; Mei, Fangchao; Li, Chen; Zuo, Teng; He, Xiaobo

    2016-08-01

    Acute renal injury caused by acute necrotizing pancreatitis (ANP) is a common complication that is associated with a high rate of mortality. Paeoniflorin is the active ingredient of paeonia radix and exhibits a number of pharmacological effects, such as anti‑inflammatory, anticancer, analgesic and immunomodulatory effects. The present study detected the potential treatment effects of paeoniflorin on acute renal injury induced by ANP in a rat model. The optimal dose of paeoniflorin for preventing acute renal injury induced by ANP was determined. Then, the possible protective mechanism of paeoniflorin was investigated. The serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 were measured with enzyme‑linked immunosorbent assay kits. Renal inflammation and apoptosis were measured by immunohistochemistry and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assay. The expression of nitric oxide in kidney tissues was also evaluated. The p38 mitogen‑activated protein kinases (MAPKs) were measured by western blotting. The results shown that paeoniflorin may ameliorate acute renal injury following ANP in rats by inhibiting inflammatory responses and renal cell apoptosis. These effects may be associated with the p38MAPK and nuclear factor‑κB signal pathway. PMID:27279569

  17. Paeoniflorin ameliorates acute necrotizing pancreatitis and pancreatitis-induced acute renal injury

    PubMed Central

    Wang, Peng; Wang, Weixing; Shi, Qiao; Zhao, Liang; Mei, Fangchao; Li, Chen; Zuo, Teng; He, Xiaobo

    2016-01-01

    Acute renal injury caused by acute necrotizing pancreatitis (ANP) is a common complication that is associated with a high rate of mortality. Paeoniflorin is the active ingredient of paeonia radix and exhibits a number of pharmacological effects, such as anti-inflammatory, anticancer, analgesic and immunomodulatory effects. The present study detected the potential treatment effects of paeoniflorin on acute renal injury induced by ANP in a rat model. The optimal dose of paeoniflorin for preventing acute renal injury induced by ANP was determined. Then, the possible protective mechanism of paeoniflorin was investigated. The serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were measured with enzyme-linked immunosorbent assay kits. Renal inflammation and apoptosis were measured by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression of nitric oxide in kidney tissues was also evaluated. The p38 mitogen-activated protein kinases (MAPKs) were measured by western blotting. The results shown that paeoniflorin may ameliorate acute renal injury following ANP in rats by inhibiting inflammatory responses and renal cell apoptosis. These effects may be associated with the p38MAPK and nuclear factor-κB signal pathway. PMID:27279569

  18. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats. PMID:27593574

  19. Tracheoinnominate fistula: a rare acute complication of penetrating neck injury.

    PubMed

    Kulyapina, Alena; Díaz, Dolores Pérez; Rodríguez, Teresa Sanchez; Fuentes, Fernando Turegano

    2015-05-01

    Penetrating injuries in the base of the neck are considered to be the most dangerous due to the potential combination of vascular and intrathoracic lesions. We describe an extremely rare case of combined injury of the trachea and innominate artery, which resulted in formation of a traumatic acute tracheoinnominate fistula. Previously, these fistulas have been described as an iatrogenic complication of tracheostomy, presenting with massive peristomal bleed or hemoptysis. This case demonstrates that a combination of lesions to vital anatomical structures in the neck can change their clinical presentation, making them extremely difficult to diagnose. PMID:24948779

  20. The perfect storm: older adults and acute kidney injury.

    PubMed

    Hain, Debra; Paixao, Rute

    2015-01-01

    Older adults have a high risk for acute kidney injury (AKI), often necessitating critical care admission. The majority of older adults live with 1 or more chronic conditions requiring multiple medications, and when faced with acute illness increased vulnerability can lead to poor health outcomes. When combined with circumstances that exacerbate chronic conditions, clinicians may witness the perfect storm. Some factors that contribute to AKI risk include the aging kidney, sepsis, polypharmacy, and nephrotoxic medications and contrast media. This paper discusses specific risks and approaches to care for older adults with AKI who are in critical care. PMID:26039649

  1. The Role of Chemokines in Acute Liver Injury

    PubMed Central

    Saiman, Yedidya; Friedman, Scott L.

    2012-01-01

    Chemokines are small molecular weight proteins primarily known to drive migration of immune cell populations. In both acute and chronic liver injury, hepatic chemokine expression is induced resulting in inflammatory cell infiltration, angiogenesis, and cell activation and survival. During acute injury, massive parenchymal cell death due to apoptosis and/or necrosis leads to chemokine production by hepatocytes, cholangiocytes, Kupffer cells, hepatic stellate cells, and sinusoidal endothelial cells. The specific chemokine profile expressed during injury is dependent on both the type and course of injury. Hepatotoxicity by acetaminophen for example leads to cellular necrosis and activation of Toll-like receptors while the inciting insult in ischemia reperfusion injury produces reactive oxygen species and subsequent production of pro-inflammatory chemokines. Chemokine expression by these cells generates a chemoattractant gradient promoting infiltration by monocytes/macrophages, NK cells, NKT cells, neutrophils, B cells, and T cells whose activity are highly regulated by the specific chemokine profiles within the liver. Additionally, resident hepatic cells express chemokine receptors both in the normal and injured liver. While the role of these receptors in normal liver has not been well described, during injury, receptor up-regulation, and chemokine engagement leads to cellular survival, proliferation, apoptosis, fibrogenesis, and expression of additional chemokines and growth factors. Hepatic-derived chemokines can therefore function in both paracrine and autocrine fashions further expanding their role in liver disease. More recently it has been appreciated that chemokines can have diverging effects depending on their temporal expression pattern and the type of injury. A better understanding of chemokine/chemokine receptor axes will therefore pave the way for development of novel targeted therapies for the treatment of liver disease. PMID:22723782

  2. Acute kidney injury and ESRD management in austere environments.

    PubMed

    Raman, Gaurav; Perkins, Robert M; Jaar, Bernard G

    2012-05-01

    Current knowledge about managing acute kidney injury in disaster situations stems mostly from lessons learned while taking care of crush syndrome patients during major earthquakes. More recently, there has been a greater focus on emergency preparedness for ESRD management. Natural or man-made disasters create an "austere environment," wherein resources to administer standard of care are limited. Advance planning and timely coordinated intervention during disasters are paramount to administer effective therapies and save lives. This article reviews the presentation and management of disaster victims with acute kidney injury and those requiring renal replacement therapies. Major contributions of some key national and international organizations in the field of disaster nephrology are highlighted. The article intends to increase awareness about nephrology care of disaster victims, among nephrology and non-nephrology providers alike. PMID:22578674

  3. Mechanical ventilation of patients with acute lung injury.

    PubMed

    Sessler, C N

    1998-10-01

    Ventilatory management of patients with acute lung injury (ALI), particularly its most severe subset, acute respiratory distress syndrome (ARDS), is complex. Newer lung protective strategies emphasize measures to enhance alveolar recruitment and avoid alveolar overdistention, thus minimizing the risk of ventilator-induced lung injury (VILI). Key components of such strategies include the use of smaller-than-conventional tidal volumes which maintain peak transpulmonary pressure below the pressure associated with overdistention, and titration of positive end-expiratory pressure to promote maximal alveolar recruitment. Novel techniques, including prone positioning, inverse ratio ventilation, tracheal gas insufflation, and high frequency ventilation, are considerations in severe ARDS. No single approach is best for all patients; adjustment of ventilatory parameters to individual characteristics, such as lung mechanics and gas exchange, is required. PMID:9891634

  4. Acute kidney injury caused by bothrops snake venom.

    PubMed

    Rodrigues Sgrignolli, Lívia; Florido Mendes, Glória Elisa; Carlos, Carla Patricia; Burdmann, Emmanuel A

    2011-01-01

    Medically important venomous snakes in Latin America belong to the genus Bothrops, Crotalus, Lachesis and Micrurus. The Bothrops genus is responsible for the majority of accidents. The WHO globally estimates 2,500,000 poisonous snakebites and 125,000 deaths annually. In its last report in 2001, the Brazilian Ministry of Health accounted 359 deaths due to snakebites, of which the Bothrops genus was responsible for 185. Snake venoms cause local and systemic damage, including acute kidney injury, which is the most important cause of death among patients surviving the early effects of envenoming by the Crotalus and Bothrops genuses. Venom-induced acute kidney injury is a frequent complication of Bothrops snakebite, carrying relevant morbidity and mortality. PMID:21757950

  5. Paneth cell-mediated multiorgan dysfunction after acute kidney injury

    PubMed Central

    Park, Sang Won; Kim, Mihwa; Kim, Joo Yun; Ham, Ahrom; Brown, Kevin M.; Mori-Akiyama, Yuko; Ouellette, André J.; D’Agati, Vivette D.; Lee, H. Thomas

    2012-01-01

    Acute kidney injury (AKI) is frequently complicated by extra-renal multi-organ injury including intestinal and hepatic dysfunction. In this study, we hypothesized that a discrete intestinal source of pro-inflammatory mediators drives multi-organ injury in response to AKI. After induction of AKI in mice by renal ischemia-reperfusion or bilateral nephrectomy, small intestinal Paneth cells increased the synthesis and release of IL-17A in conjunction with severe intestinal apoptosis and inflammation. We also detected significantly increased IL-17A in portal and systemic circulation after AKI. Intestinal macrophages appear to transport released Paneth cell granule constituents induced by AKI, away from the base of the crypts into the liver. Genetic or pharmacologic depletion of Paneth cells decreased small intestinal IL-17A secretion and plasma IL-17A levels significantly and attenuated intestinal, hepatic, and renal injury after AKI. Similarly, portal delivery of IL-17A in macrophage depleted mice decreased markedly, and intestinal, hepatic, and renal injury following AKI was attenuated without affecting intestinal IL-17A generation. In conclusion, AKI induces IL-17A synthesis and secretion by Paneth cells to initiate intestinal and hepatic injury by hepatic and systemic delivery of IL-17A by macrophages. Modulation of Paneth cell dysregulation may have therapeutic implications by reducing systemic complications arising from AKI. PMID:23109723

  6. Suramin protects from cisplatin-induced acute kidney injury.

    PubMed

    Dupre, Tess V; Doll, Mark A; Shah, Parag P; Sharp, Cierra N; Kiefer, Alex; Scherzer, Michael T; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G; Beverly, Levi J; Siskind, Leah J

    2016-02-01

    Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

  7. [Uncaria tomentosa and acute ischemic kidney injury in rats].

    PubMed

    de Fátima Fernandes Vattimo, Maria; da Silva, Natalia Oliveira

    2011-03-01

    The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat's claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities. PMID:21445508

  8. Presumptive acute lung injury following multiple surgeries in a cat

    PubMed Central

    Katayama, Masaaki; Okamura, Yasuhiko; Katayama, Rieko; Sasaki, Jun; Shimamura, Shunsuke; Uzuka, Yuji; Kamishina, Hiroaki; Nezu, Yoshinori

    2013-01-01

    A 12-year-old, 3.5-kg spayed female domestic shorthair cat had a tracheal mass identified as malignant B-cell lymphoma. The cat had tracheal resection and subsequently developed laryngeal paralysis. Due to multiple episodes of respiratory distress the cat subsequently had tracheal surgeries. Finally, the cat had a sudden onset of severe respiratory distress and collapsed. Computed tomography imaging and arterial blood gas analysis supported a diagnosis of acute lung injury. PMID:24082167

  9. Iron, hormesis, and protection in acute kidney injury.

    PubMed

    Swaminathan, Sundararaman

    2016-07-01

    Iron is critical for cellular, organismal, and possibly universal existence. Use of iron complexes to treat human diseases is ancient and is described in detail in Ayurveda/Siddha systems of medicine. Old aphorisms from Siddha medicine ("Alavukku Minjinal Amirdhamum Nanjagum," an elixir turns poisonous when taken in excess) and Paracelsus ("Die Dosis macht das Gift," the dose makes the poison) are of practical relevance in understanding the role of this ancient metal in acute kidney injury. PMID:27312440

  10. [Sodium dichloroisocyanurate-induced acute lung injury in a child].

    PubMed

    Wiel, E; Sicot, J; Leteurtre, S; Binoche, A; Nisse, P; Assez, N

    2013-04-01

    Intoxication, by cyanurate and its chlorated derivatives in children, is increasingly reported in the literature due to accidental ingestion compared to accidental inhalation. We report a case in a 5-year-old child who presented with acute lung injury due to accidental inhalation of gas formed after a reaction of sodium dichloroisocyanurate tablets with water. Prevention remains the best way to reduce the risk of children being intoxicated by inhalation of the gas formed after contact of tablets with water. PMID:23433843

  11. Transfusion-related acute lung injury; clinical perspectives

    PubMed Central

    Kim, Jeongmin

    2015-01-01

    Transfusion-related acute lung injury (TRALI) was introduced in 1983 to describe a clinical syndrome seen within 6 h of a plasma-containing blood products transfusion. TRALI is a rare transfusion complication; however, the FDA has suggested that TRALI is the leading cause of transfusion-related mortality. Understanding the pathogenesis of TRALI will facilitate adopting preventive strategies, such as deferring high plasma volume female product donors. This review outlines the clinical features, pathogenesis, treatment, and prevention of TRALI. PMID:25844126

  12. Acetaminophen-induced acute liver injury in HCV transgenic mice

    SciTech Connect

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  13. Drug and alcohol abuse in patients with acute burn injuries.

    PubMed

    Swenson, J R; Dimsdale, J E; Rockwell, E; Carroll, W; Hansbrough, J

    1991-01-01

    We reviewed records of adult patients admitted to our burn unit who were reported to abuse drugs or alcohol from 1985 to 1988. The proportion of patients reported as abusing drugs increased significantly from 1987 to 1988, compared to previous years. However, there was no increase in the proportion of patients reported to abuse alcohol. Patients identified as abusing drugs had longer hospital stays, compared to patients who were not reported to abuse substances. Methamphetamine and cocaine were the drugs most often abused by patients who abused drugs or both drugs and alcohol. Mechanisms of burn injury in these patients included "accidental" burn injury related to acute intoxication, and self-injury due to psychosis or depression. PMID:1882020

  14. Acute gastroduodenal injury after ingestion of diluted herbicide pendimethalin.

    PubMed

    Tsukada, K; Azuhata, H; Katoh, H; Kuwano, H

    2009-03-01

    The herbicide, pendimethalin, is used worldwide, but its acute toxicity is not yet widely known. There have been some reported acute pendimethalin poisoning cases in humans and most of them intentionally ingested the concentrated formulation. We describe a 73-year-old man who developed corrosive gastroduodenal injury after accidental ingestion of the diluted (300 times with water) pendimethalin formulation. He had a history of reflux oesophagitis and had been taking omeprazol (10 mg/day) for a year. He consumed alcohol two hours after the accidental ingestion and then had nausea and epigastric pain. Endoscopy performed three days post-exposure revealed gastroduodenal injury. As he had consumed alcohol every day for years and had no history of gastroduodenal ulcer, the accidental ingestion may be associated with this injury. He was successfully treated by increasing his dosage of omeprazol (20 mg/day) for two weeks. This case indicates that ingestion of a small quantity of pendimethalin can provoke gastroduodenal injury. PMID:19352552

  15. Pathophysiology of cisplatin-induced acute kidney injury.

    PubMed

    Ozkok, Abdullah; Edelstein, Charles L

    2014-01-01

    Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality. PMID:25165721

  16. Targeted Lipid Profiling Discovers Plasma Biomarkers of Acute Brain Injury

    PubMed Central

    Sheth, Sunil A.; Iavarone, Anthony T.; Liebeskind, David S.; Won, Seok Joon; Swanson, Raymond A.

    2015-01-01

    Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain. Here we examined the feasibility of using SLs as biomarkers for acute brain injury. A rat model of traumatic brain injury (TBI) and a mouse model of stroke were used to identify candidate SL species though our mass-spectrometry based lipid profiling approach. Plasma samples collected after TBI in the rat showed large increases in many circulating SLs following injury, and larger lesions produced proportionately larger increases. Plasma samples collected 24 hours after stroke in mice similarly revealed a large increase in many SLs. We constructed an SL score (sum of the two SL species showing the largest relative increases in the mouse stroke model) and then evaluated the diagnostic value of this score on a small sample of patients (n = 14) who presented with acute stroke symptoms. Patients with true stroke had significantly higher SL scores than patients found to have non-stroke causes of their symptoms. The SL score correlated with the volume of ischemic brain tissue. These results demonstrate the feasibility of using lipid biomarkers to diagnose brain injury. Future studies will be needed to further characterize the diagnostic utility of this approach and to transition to an assay method applicable to clinical settings. PMID:26076478

  17. Anemia management after acute brain injury.

    PubMed

    Lelubre, Christophe; Bouzat, Pierre; Crippa, Ilaria Alice; Taccone, Fabio Silvio

    2016-01-01

    Anemia is frequent among brain-injured patients, where it has been associated with an increased risk of poor outcome. The pathophysiology of anemia in this patient population remains multifactorial; moreover, whether anemia merely reflects a higher severity of the underlying disease or is a significant determinant of the neurological recovery of such patients remains unclear. Interestingly, the effects of red blood cell transfusions (RBCT) in moderately anemic patients remain controversial; although hemoglobin levels are increased, different studies observed only a modest and inconsistent improvement in cerebral oxygenation after RBCT and raised serious concerns about the risk of increased complications. Thus, considering this "blood transfusion anemia paradox", the optimal hemoglobin level to trigger RBCT in brain-injured patients has not been defined yet; also, there is insufficient evidence to provide strong recommendations regarding which hemoglobin level to target and which associated transfusion strategy (restrictive versus liberal) to select in this patient population. We summarize in this review article the more relevant studies evaluating the effects of anemia and RBCT in patients with an acute neurological condition; also, we propose some potential strategies to optimize transfusion management in such patients. PMID:27311626

  18. Pathophysiology of pulmonary hypertension in acute lung injury

    PubMed Central

    Price, Laura C.; McAuley, Danny F.; Marino, Philip S.; Finney, Simon J.; Griffiths, Mark J.

    2012-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI. PMID:22246001

  19. Imaging of acute thoracic injury: the advent of MDCT screening.

    PubMed

    Mirvis, Stuart E

    2005-10-01

    Chest radiography remains the primary screening study for the assessment of victims of chest trauma, but computed tomography (CT), particularly multidetector CT (MDCT), has progressively changed the imaging approach to these patients. MDCT acquires thinner sections with greater speed, allowing higher quality axial images and nonaxial reformations than conventional or single-detector helical CT. The speed of MDCT, both in acquiring data and in reconstructing images, makes the performance of total body surveys in the blunt polytrauma patient practicable. In general, CT has been well documented to offer major advantages over chest radiography in both screening for thoracic injuries and in characterizing such injuries. This capacity has been enhanced by the application of multichannel data acquisition. The greater sensitivity of MDCT has been well demonstrated in diagnosing vascular and diaphragmatic injuries. This article reviews current concepts of diagnostic imaging in acute chest trauma from blunt force and penetrating mechanisms emphasizing the spectrum of diagnostic imaging findings for various injuries, based primarily on radiographic and CT appearances. The advantages of MDCT for selected injuries are emphasized. PMID:16274001

  20. Biomarkers and acute brain injuries: interest and limits

    PubMed Central

    2014-01-01

    For patients presenting with acute brain injury (such as traumatic brain injury, subarachnoid haemorrhage and stroke), the diagnosis and identification of intracerebral lesions and evaluation of the severity, prognosis and treatment efficacy can be challenging. The complexity and heterogeneity of lesions after brain injury are most probably responsible for this difficulty. Patients with apparently comparable brain lesions on imaging may have different neurological outcomes or responses to therapy. In recent years, plasmatic and cerebrospinal fluid biomarkers have emerged as possible tools to distinguish between the different pathophysiological processes. This review aims to summarise the plasmatic and cerebrospinal fluid biomarkers evaluated in subarachnoid haemorrhage, traumatic brain injury and stroke, and to clarify their related interests and limits for diagnosis and prognosis. For subarachnoid haemorrhage, particular interest has been focused on the biomarkers used to predict vasospasm and cerebral ischaemia. The efficacy of biomarkers in predicting the severity and outcome of traumatic brain injury has been stressed. The very early diagnostic performance of biomarkers and their ability to discriminate ischaemic from haemorrhagic stroke were studied. PMID:25029344

  1. Prospective Study on the Clinical Course and Outcomes in Transfusion-Related Acute Lung Injury

    PubMed Central

    Looney, Mark R.; Roubinian, Nareg; Gajic, Ognjen; Gropper, Michael A.; Hubmayr, Rolf D.; Lowell, Clifford A.; Bacchetti, Peter; Wilson, Gregory; Koenigsberg, Monique; Lee, Deanna C.; Wu, Ping; Grimes, Barbara; Norris, Philip J.; Murphy, Edward L.; Gandhi, Manish J.; Winters, Jeffrey L.; Mair, David C.; Schuller, Randy M.; Hirschler, Nora V.; Rosen, Rosa Sanchez; Matthay, Michael A.; Toy, Pearl

    2014-01-01

    Objective Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases. Design Prospective case study with controls. Setting University of California, San Francisco and Mayo Clinic, Rochester. Patients We prospectively enrolled 89 patients with transfusion-related acute lung injury, 164 transfused controls, and 145 patients with possible transfusion-related acute lung injury. Interventions None. Measurements and Main Results Patients with transfusion-related acute lung injury had fever, tachycardia, tachypnea, hypotension, and prolonged hypoxemia compared with controls. Of the patients with transfusion-related acute lung injury, 29 of 37 patients (78%) required initiation of mechanical ventilation and 13 of 53 (25%) required initiation of vasopressors. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury had an increased duration of mechanical ventilation and increased days in the ICU and hospital compared with controls. There were 15 of 89 patients with transfusion-related acute lung injury (17%) who died, whereas 61 of 145 patients with possible transfusion-related acute lung injury (42%) died and 7 of 164 of controls (4%) died. Patients with transfusion-related acute lung injury had evidence of more systemic inflammation with increases in circulating neutrophils and a decrease in platelets compared with controls. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury also had a statistically significant increase in plasma interleukin-8, interleukin-10, and interleukin-1 receptor antagonist posttransfusion compared with controls. Conclusions In conclusion, transfusion-related acute lung injury produced a condition

  2. Acute traumatic spinal injury following bicycle accidents: a report of three cases.

    PubMed

    McGoldrick, Niall P; Green, Connor; Burke, Neil; Synnott, Keith

    2012-06-01

    Although the vast majority of injuries suffered while cycling are minor, acute spinal injuries have been reported. We describe three cases of acute spinal injury occurring while cycling. All three patients reported being thrown over the handlebars, while travelling downhill at speed. Two of the cases resulted in profound neurological deficit. These cases show that there is a spectrum of spinal injury due to bicycle accidents, ranging from no neurological deficit to profound insult, and from high cervical injury to mid-thoracic spinal injury. In cases of bicycle accidents, increased awareness of the possibility of such spinal injury is advisable. PMID:22822586

  3. Neuroprotection and Acute Spinal Cord Injury: A Reappraisal

    PubMed Central

    Hall, Edward D.; Springer, Joe E.

    2004-01-01

    Summary: It has long been recognized that much of the post-traumatic degeneration of the spinal cord following injury is caused by a multi-factorial secondary injury process that occurs during the first minutes, hours, and days after spinal cord injury (SCI). A key biochemical event in that process is reactive oxygen-induced lipid peroxidation (LP). In 1990 the results of the Second National Acute Spinal Cord Injury Study (NASCIS II) were published, which showed that the administration of a high-dose regimen of the glucocorticoid steroid methylprednisolone (MP), which had been previously shown to inhibit post-traumatic LP in animal models of SCI, could improve neurological recovery in spinal-cord-injured humans. This resulted in the registration of high-dose MP for acute SCI in several countries, although not in the U.S. Nevertheless, this treatment quickly became the standard of care for acute SCI since the drug was already on the U.S. market for many other indications. Subsequently, it was demonstrated that the non-glucocorticoid 21-aminosteroid tirilazad could duplicate the antioxidant neuroprotective efficacy of MP in SCI models, and evidence of human efficacy was obtained in a third NASCIS trial (NASCIS III). In recent years, the use of high-dose MP in acute SCI has become controversial largely on the basis of the risk of serious adverse effects versus what is perceived to be on average a modest neurological benefit. The opiate receptor antagonist naloxone was also tested in NASCIS II based upon the demonstration of its beneficial effects in SCI models. Although it did not a significant overall effect, some evidence of efficacy was seen in incomplete (i.e., paretic) patients. The monosialoganglioside GM1 has also been examined in a recently completed clinical trial in which the patients first received high-dose MP treatment. However, GM1 failed to show any evidence of a significant enhancement in the extent of neurological recovery over the level afforded by

  4. [Sequential changes in acute phase reactant proteins and complement activation in patients with acute head injuries].

    PubMed

    Ikeda, Y; Matsuura, H; Nakazawa, S

    1987-12-01

    The role of immunological mechanisms in head injury is not clearly defined. In this study we investigated the immunological function in patients with acute head injuries. Serum acute phase reactant proteins (APRP), complement activation and immunoglobulines as immunological parameters were studied. APRP are produced in the liver and increase in cancer patients as well as those with acute and chronic inflammations, trauma and autoimmune diseases. APRP are known to be one of the immunosuppressive factors in the serum. Forty patients with acute head injuries were studied. Thirty-four patients were male and six patients were female, ages ranged from 12 to 81 years. Serial blood samples were obtained during the first seven days of trauma. The Glasgow Coma Score (GCS) were recorded at the time of admission for all patients. Clinical outcome was assessed at the time of discharge according to the Glasgow Outcome Scale. The "good" group consisted of patients with good recovery or moderate disability. The "bad" group consisted of patients with severe disability, persistent vegetative state and death. The concentrations of immunoglobulines (IgG, IgM, IgA) were within normal range and humoral immunity was not affected. Complement activation at the time of admission was closely related to GCS (p less than 0.01), but the levels of C4, C3, and C3 activator except for these of CH50 were within normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2451531

  5. Fluid Balance, Diuretic Use, and Mortality in Acute Kidney Injury

    PubMed Central

    Estrella, Michelle M.; Coresh, Josef; Brower, Roy G.; Liu, Kathleen D.

    2011-01-01

    Summary Background and objectives Management of volume status in patients with acute kidney injury (AKI) is complex, and the role of diuretics is controversial. The primary objective was to elucidate the association between fluid balance, diuretic use, and short-term mortality after AKI in critically ill patients. Design, setting, participants, & measurements Using data from the Fluid and Catheter Treatment Trial (FACTT), a multicenter, randomized controlled trial evaluating a conservative versus liberal fluid-management strategy in 1000 patients with acute lung injury (ALI), we evaluated the association of post-renal injury fluid balance and diuretic use with 60-day mortality in patients who developed AKI, as defined by the AKI Network criteria. Results 306 patients developed AKI in the first 2 study days and were included in our analysis. There were 137 in the fluid-liberal arm and 169 in the fluid-conservative arm (P = 0.04). Baseline characteristics were similar between groups. Post-AKI fluid balance was significantly associated with mortality in both crude and adjusted analysis. Higher post-AKI furosemide doses had a protective effect on mortality but no significant effect after adjustment for post-AKI fluid balance. There was no threshold dose of furosemide above which mortality increased. Conclusions A positive fluid balance after AKI was strongly associated with mortality. Post-AKI diuretic therapy was associated with 60-day patient survival in FACTT patients with ALI; this effect may be mediated by fluid balance. PMID:21393482

  6. Acute Injuries among Professional Boxers in New York State: A Two-Year Survey.

    ERIC Educational Resources Information Center

    Jordan, Barry D.; Campbell, Edwin A.

    1988-01-01

    From August 1982 through July 1984, all acute boxing injuries among professional boxers in New York State were reviewed in order to classify them as craniocerebral or other injuries. Results and methodology are discussed. (Author/MT)

  7. Biomarkers of acute kidney injury and associations with short- and long-term outcomes

    PubMed Central

    Schaub, Jennifer A.; Parikh, Chirag R.

    2016-01-01

    Acute kidney injury is strongly associated with increased mortality and other adverse outcomes. Medical researchers have intensively investigated novel biomarkers to predict short- and long-term outcomes of acute kidney injury in many patient care settings, such as cardiac surgery, intensive care units, heart failure, and transplant. Future research should focus on leveraging this relationship to improve enrollment for clinical trials of acute kidney injury. PMID:27239295

  8. [Acute lung injury as a consequence of blood transfusion].

    PubMed

    Rodríguez-Moyado, Héctor

    2011-01-01

    Acute lung injury (ALI) has been recognized as a consequence of blood transfusion (BT) since 1978; the Food and Drug Administration, has classified it as the third BT mortality issue, in 2004, and in first place related with ALI. It can be mainly detected as: Acute respiratory distress syndrome (ARDS), transfusion associated circulatory overload (TACO) and transfusion related acute lung injury (TRALI). The clinical onset is: severe dyspnea, bilateral lung infiltration and low oxygen saturation. In USA, ARDS has an incidence of three to 22.4 cases/100 000 inhabitants, with 58.3 % mortality. TACO and TRALI are less frequent; they have been reported according to the number of transfusions: one in 1275 to 6000 for TRALI and one in 356 transfusions for TACO. Mortality is reported from two to 20 % in TRALI and 20 % in TACO. Antileukocyte antibodies in blood donors plasma, caused TRALI in 89 % of cases; also it has been found antigen specificity against leukocyte blood receptor in 59 %. The UCI patients who received a BT have ALI as a complication in 40 % of cases. The capillary pulmonary endothelia is the target of leukocyte antibodies and also plasma biologic modifiers of the stored plasma, most probable like a Sanarelli-Shwar-tzman phenomenon. PMID:21838994

  9. Innate danger signals in acute injury: From bench to bedside.

    PubMed

    Fontaine, Mathieu; Lepape, Alain; Piriou, Vincent; Venet, Fabienne; Friggeri, Arnaud

    2016-08-01

    The description of the systemic inflammatory response syndrome (SIRS) as a reaction to numerous insults marked a turning point in the understanding of acute critical states, which are intensive care basic cases. This concept highlighted the final inflammatory response features whichever the injury mechanism is: infectious, or non-infectious such as extensive burns, traumas, major surgery or acute pancreatitis. In these cases of severe non-infectious insult, many endogenous mediators are released. Like infectious agents components, they can activate the immune system (via common signaling pathways) and initiate an inflammatory response. They are danger signals or alarmins. These molecules generally play an intracellular physiological role and acquire new functions when released in extracellular space. Many progresses brought new information on these molecules and on their function in infectious and non-infectious inflammation. These danger signals can be used as biomarkers and provide new pathophysiological and therapeutic approaches, particularly for immune dysfunctions occurring after an acute injury. We present herein the danger model, the main danger signals and the clinical consequences. PMID:26987739

  10. Contrast-Induced Acute Kidney Injury: An Update.

    PubMed

    Chalikias, George; Drosos, Ioannis; Tziakas, Dimitrios N

    2016-04-01

    Contrast-induced acute kidney injury (CI-AKI) is defined as an abrupt deterioration in renal function associated with the administration of iodinated contrast media. This type of acute kidney injury is frequently encountered as a complication of percutaneous coronary intervention (PCI) and is associated with adverse short- and long-term outcomes including mainly mortality, cardiovascular morbidity and prolongation of hospitalization. The incidence of CI-AKI after PCI ranges from 2 to 20 % according to baseline kidney function. It may also range according to the clinical setting, being higher after emergency PCI. The primary manifestation is a small decline in kidney function, occurring 1 to 3 days after the procedure. Kidney function usually returns to preexisting levels within 7 days. Incidence of acute renal failure requiring dialysis following PCI is rare (<1 %). The present article aims to review up-to-date published data concerning diagnosis, definition, epidemiology and prognosis of this novel in-hospital epidemic. PMID:26780748

  11. Role of liver progenitors in acute liver injury

    PubMed Central

    Best, Jan; Dollé, Laurent; Manka, Paul; Coombes, Jason; van Grunsven, Leo A.; Syn, Wing-Kin

    2013-01-01

    Acute liver failure (ALF) results from the acute and rapid loss of hepatocyte function and frequently exhibits a fulminant course, characterized by high mortality in the absence of immediate state-of-the-art intensive care and/or emergency liver transplantation (ELT). The role of hepatocyte-mediated liver regeneration during acute and chronic liver injury has been extensively investigated, and recent studies suggest that hepatocytes are not exclusively responsible for the regeneration of the injured liver during fulminant liver injury. Liver progenitor cells (LPC) (or resident liver stem cells) are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. This review aims to provide an overview of the role of the LPC population during ALF, and the role of putative cytokines, growth factors, mitogens, and hormones in the LPC response. We will highlight the potential interaction among cellular compartments during ALF, and discuss the possible prognostic value of the LPC response on ALF outcomes. PMID:24133449

  12. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products. PMID:25510780

  13. Renalase and Biomarkers of Contrast-Induced Acute Kidney Injury

    PubMed Central

    Wybraniec, Maciej T.; Mizia-Stec, Katarzyna

    2015-01-01

    Background Contrast-induced acute kidney injury (CI-AKI) remains one of the crucial issues related to the development of invasive cardiology. The massive use of contrast media exposes patients to a great risk of contrast-induced nephropathy and chronic kidney disease development, and increases morbidity and mortality rates. The serum creatinine concentration does not allow for a timely and accurate CI-AKI diagnosis; hence numerous other biomarkers of renal injury have been proposed. Renalase, a novel catecholamine-metabolizing amine oxidase, is synthesized mainly in proximal tubular cells and secreted into urine and blood. It is primarily engaged in the degradation of circulating catecholamines. Notwithstanding its key role in blood pressure regulation, renalase remains a potential CI-AKI biomarker, which was shown to be markedly downregulated in the aftermath of renal injury. In this sense, renalase appears to be the first CI-AKI marker revealing an actual loss of renal function and indicating disease severity. Summary The purpose of this review is to summarize the contemporary knowledge about the application of novel biomarkers of CI-AKI and to highlight the potential role of renalase as a functional marker of contrast-induced renal injury. Key Messages Renalase may constitute a missing biochemical link in the mutual interplay between kidney and cardiac pathology known as the cardiorenal syndrome. PMID:27194994

  14. Protein methionine oxidation augments reperfusion injury in acute ischemic stroke

    PubMed Central

    Gu, Sean X.; Blokhin, Ilya O.; Wilson, Katina M.; Dhanesha, Nirav; Doddapattar, Prakash; Grumbach, Isabella M.; Chauhan, Anil K.; Lentz, Steven R.

    2016-01-01

    Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB–dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke. PMID:27294204

  15. Management of Acute Lumbar Injuries in the Workplace.

    PubMed

    Lurati, Ann Regina

    2016-01-01

    Occupational acute lumbar injuries are a common injury. One intervention that is unique to occupational health is the determination of the amount of physical activity that an injured worker can perform without increasing the risk of further injury. Clinical recommendations suggest that workers continue to stay active; however, it is still the clinician's responsibility to determine the level of activity. The level of work activity is determined on a case-to-case basis and is done by evaluating the physical capacity of an injured worker and the job description. Current evidence-based guidelines suggest that staying active may actually reduce pain levels. The purpose of this evidence-based literature review is to outline the proper assessment and management of workers who have sustained a work-related low back injury. The related literature has been reviewed as well as red flags for more severe neurological conditions that require more in-depth evaluation. Determining the safe level of activity and guided return to work have been discussed. PMID:27187219

  16. Cell-specific translational profiling in acute kidney injury

    PubMed Central

    Liu, Jing; Krautzberger, A. Michaela; Sui, Shannan H.; Hofmann, Oliver M.; Chen, Ying; Baetscher, Manfred; Grgic, Ivica; Kumar, Sanjeev; Humphreys, Benjamin; Hide, Winston A.; McMahon, Andrew P.

    2014-01-01

    Acute kidney injury (AKI) promotes an abrupt loss of kidney function that results in substantial morbidity and mortality. Considerable effort has gone toward identification of diagnostic biomarkers and analysis of AKI-associated molecular events; however, most studies have adopted organ-wide approaches and have not elucidated the interplay among different cell types involved in AKI pathophysiology. To better characterize AKI-associated molecular and cellular events, we developed a mouse line that enables the identification of translational profiles in specific cell types. This strategy relies on CRE recombinase–dependent activation of an EGFP-tagged L10a ribosomal protein subunit, which allows translating ribosome affinity purification (TRAP) of mRNA populations in CRE-expressing cells. Combining this mouse line with cell type–specific CRE-driver lines, we identified distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Twenty-four hours following IRI, distinct translational signatures were identified in the nephron, kidney interstitial cell populations, vascular endothelium, and macrophages/monocytes. Furthermore, TRAP captured known IRI-associated markers, validating this approach. Biological function annotation, canonical pathway analysis, and in situ analysis of identified response genes provided insight into cell-specific injury signatures. Our study provides a deep, cell-based view of early injury-associated molecular events in AKI and documents a versatile, genetic tool to monitor cell-specific and temporal-specific biological processes in disease modeling. PMID:24569379

  17. Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury.

    PubMed

    McKee, Robert A; Wingert, Rebecca A

    2016-01-01

    The kidneys are susceptible to harm from exposure to chemicals they filter from the bloodstream. This can lead to organ injury associated with a rapid decline in renal function and development of the clinical syndrome known as acute kidney injury (AKI). Pharmacological agents used to treat medical circumstances ranging from bacterial infection to cancer, when administered individually or in combination with other drugs, can initiate AKI. Zebrafish are a useful animal model to study the chemical effects on renal function in vivo, as they form an embryonic kidney comprised of nephron functional units that are conserved with higher vertebrates, including humans. Further, zebrafish can be utilized to perform genetic and chemical screens, which provide opportunities to elucidate the cellular and molecular facets of AKI and develop therapeutic strategies such as the identification of nephroprotective molecules. Here, we demonstrate how microinjection into the zebrafish embryo can be utilized as a paradigm for nephrotoxin studies. PMID:27500823

  18. Autophagy is activated to protect against endotoxic acute kidney injury.

    PubMed

    Mei, Shuqin; Livingston, Man; Hao, Jielu; Li, Lin; Mei, Changlin; Dong, Zheng

    2016-01-01

    Endotoxemia in sepsis, characterized by systemic inflammation, is a major cause of acute kidney injury (AKI) in hospitalized patients, especially in intensive care unit; however the underlying pathogenesis is poorly understood. Autophagy is a conserved, cellular catabolic pathway that plays crucial roles in cellular homeostasis including the maintenance of cellular function and viability. The regulation and role of autophagy in septic or endotoxic AKI remains unclear. Here we show that autophagy was induced in kidney tubular cells in mice by the endotoxin lipopolysaccharide (LPS). Pharmacological inhibition of autophagy with chloroquine enhanced LPS-induced AKI. Moreover, specific ablation of autophagy gene 7 (Atg7) from kidney proximal tubules worsened LPS-induced AKI. Together, the results demonstrate convincing evidence of autophagy activation in endotoxic kidney injury and support a renoprotective role of autophagy in kidney tubules. PMID:26916346

  19. Snakebite-induced acute kidney injury in Latin America.

    PubMed

    Pinho, Fábia M Oliveira; Yu, Luis; Burdmann, Emmanuel A

    2008-07-01

    There are 4 genera of venomous snakes in Latin America: Bothrops, Crotalus, Lachesis, and Micrurus. Acute kidney injury (AKI) has been reported consistently after Bothrops and Crotalus envenomations. In fact, these 2 genera of snakes are responsible, along with the Russell's viper, for the majority of cases of snakebite-induced AKI reported worldwide. Although the Bothrops snakes are the leading cause of venomous snakebites in Latin America, the absolute number of AKI cases seen after Bothrops and Crotalus snakebites is similar. In this article the main characteristics of Bothrops and Crotalus snakes and their venoms, the clinical picture, and the pattern of accidents, risk factors, and mechanisms of renal injury are reviewed. PMID:18620958

  20. Immediate Consequences of Acute Kidney Injury: The Impact of Traditional and Nontraditional Complications on Mortality in Acute Kidney Injury.

    PubMed

    Faubel, Sarah; Shah, Pratik B

    2016-05-01

    Acute kidney injury (AKI) that requires renal replacement therapy is associated with a mortality rate that exceeds 50% in the intensive care unit, which is greater than other serious illnesses such as acute lung injury and myocardial infarction. Much information is now available regarding the complications of AKI that contribute to mortality and may be usefully categorized as "traditional" and "nontraditional". Traditional complications are the long-recognized complications of AKI such as hyperkalemia, acidosis, and volume overload, which may be typically corrected with renal replacement therapy. "Nontraditional" complications include complications such as sepsis, lung injury, and heart failure that may arise due to the effects of AKI on inflammatory cytokines, immune function, and cell death pathways such as apoptosis. In this review, we discuss both traditional and nontraditional complications of AKI with a focus on factors that contribute to mortality, considering both pathophysiology and potential remedies. Because AKI is the most common inpatient consult to nephrologists, it is essential to be aware of the complications of AKI that contribute to mortality to devise appropriate treatment strategies to prevent and manage AKI complications with the ultimate goal of reducing the unacceptably high mortality rate of AKI. PMID:27113694

  1. Bilateral ureteric stones: an unusual cause of acute kidney injury.

    PubMed

    Sumner, Daniel; Rehnberg, Lucas; Kler, Aaron

    2016-01-01

    A 49-year-old man presented to the accident and emergency department, with a short history of vague abdominal pain, abdominal distension and two episodes of frank haematuria. A plain chest film showed dilated loops of large bowel and blood results on admission showed an acute kidney injury (stage 3). A diagnosis of bowel obstruction was made initially but a CT scan of the abdomen showed bilateral obstructing calculi. After initial resuscitation, the patient had bilateral ultrasound-guided nephrostomies and haemofiltration. He later underwent bilateral antegrade ureteric stenting. A decision will later be made on whether or not he is fit enough to undergo ureteroscopy and laser stone fragmentation. PMID:27030462

  2. Dynamic Multiphoton Microscopy: Focusing Light on Acute Kidney Injury

    PubMed Central

    Molitoris, Bruce A.

    2014-01-01

    Acute kidney injury (AKI) is a major global health problem; much research has been conducted on AKI, and numerous agents have shown benefit in animal studies, but none have translated into treatments. There is, therefore, a pressing unmet need to increase knowledge of the pathophysiology of AKI. Multiphoton microscopy (MPM) provides a tool to non-invasively visualize dynamic events in real time and at high resolution in rodent kidneys, and in this article we review its application to study novel mechanisms and treatments in different forms of AKI. PMID:25180263

  3. Acute traumatic cord injury associated with ossified ligamentum flavum.

    PubMed

    Kow, Chien Yew; Chan, Patrick; Etherington, Greg; Rosenfeld, Jeffrey V

    2016-08-01

    Ossification of the ligamentum flavum (OLF) is an uncommon condition, which usually occurs amongst people of Asian descent, and most commonly in the thoracic spine region. Whilst often asymptomatic, OLF can cause spinal canal stenosis, with patients presenting with back pain, posterior cord syndrome or myelopathy. We present a rare case of acute spinal cord injury associated with OLF after a kite surfing accident, with the resulting paraplegia partially improved after decompression was performed. The prevalence, presentation and management of OLF are also discussed. PMID:27052256

  4. Imaging of Spinal Cord Injury: Acute Cervical Spinal Cord Injury, Cervical Spondylotic Myelopathy, and Cord Herniation.

    PubMed

    Talekar, Kiran; Poplawski, Michael; Hegde, Rahul; Cox, Mougnyan; Flanders, Adam

    2016-10-01

    We review the pathophysiology and imaging findings of acute traumatic spinal cord injury (SCI), cervical spondylotic myelopathy, and briefly review the much less common cord herniation as a unique cause of myelopathy. Acute traumatic SCI is devastating to the patient and the costs to society are staggering. There are currently no "cures" for SCI and the only accepted pharmacologic treatment regimen for traumatic SCI is currently being questioned. Evaluation and prognostication of SCI is a demanding area with significant deficiencies, including lack of biomarkers. Accurate classification of SCI is heavily dependent on a good clinical examination, the results of which can vary substantially based upon the patient׳s condition or comorbidities and the skills of the examiner. Moreover, the full extent of a patients׳ neurologic injury may not become apparent for days after injury; by then, therapeutic response may be limited. Although magnetic resonance imaging (MRI) is the best imaging modality for the evaluation of spinal cord parenchyma, conventional MR techniques do not appear to differentiate edema from axonal injury. Recently, it is proposed that in addition to characterizing the anatomic extent of injury, metrics derived from conventional MRI and diffusion tensor imaging, in conjunction with the neurological examination, can serve as a reliable objective biomarker for determination of the extent of neurologic injury and early identification of patients who would benefit from treatment. Cervical spondylosis is a common disorder affecting predominantly the elderly with a potential to narrow the spinal canal and thereby impinge or compress upon the neural elements leading to cervical spondylotic myelopathy and radiculopathy. It is the commonest nontraumatic cause of spinal cord disorder in adults. Imaging plays an important role in grading the severity of spondylosis and detecting cord abnormalities suggesting myelopathy. PMID:27616315

  5. Preventing Flow-Metabolism Uncoupling Acutely Reduces Axonal Injury after Traumatic Brain Injury

    PubMed Central

    Mironova, Yevgeniya A.; Chen, Szu-Fu; Richards, Hugh K.; Pickard, John D.

    2012-01-01

    Abstract We have previously presented evidence that the development of secondary traumatic axonal injury is related to the degree of local cerebral blood flow (LCBF) and flow-metabolism uncoupling. We have now tested the hypothesis that augmenting LCBF in the acute stages after brain injury prevents further axonal injury. Data were acquired from rats with or without acetazolamide (ACZ) that was administered immediately following controlled cortical impact injury to increase cortical LCBF. Local cerebral metabolic rate for glucose (LCMRglc) and LCBF measurements were obtained 3 h post-trauma in the same rat via 18F-fluorodeoxyglucose and 14C-iodoantipyrine co-registered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections, and in additional groups at 24 h used to assess different populations of injured axons stereologically. ACZ treatment significantly and globally elevated LCBF twofold above untreated-injured rats at 3 h (p<0.05), but did not significantly affect LCMRglc. As a result, ipsilateral LCMRglc:LCBF ratios were reduced by twofold to sham-control levels, and the density of β-APP-stained axons at 24 h was significantly reduced in most brain regions compared to the untreated-injured group (p<0.01). Furthermore, early LCBF augmentation prevented the injury-associated increase in the number of stained axons from 3–24 h. Additional robust stereological analysis of impaired axonal transport and neurofilament compaction in the corpus callosum and cingulum underlying the injury core confirmed the amelioration of β-APP axon density, and showed a trend, but no significant effect, on RMO14-positive axons. These data underline the importance of maintaining flow-metabolism coupling immediately after injury in order to prevent further axonal injury, in at least one population of injured axons. PMID:22321027

  6. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats

    PubMed Central

    Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F.; Hua, Ya

    2014-01-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron level in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 hours (lateral ventricle volume: 24.1±3.0 vs. 9.9±0.2 mm3 in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm3 in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI. PMID:24935175

  7. Renal and urological diseases of the newborn neonatal acute kidney injury.

    PubMed

    Mistry, Kirtida

    2014-01-01

    Survival of critically ill neonates in the intensive care unit has improved over the past decades reflecting improvements in obstetric, delivery room and neonatal intensive care, however, morbidity remains significant. Acute kidney injury is a common occurrence in these neonates and despite improved understanding of the pathophysiology and management of acute kidney injury in full term and preterm infants, the mortality remains as high as 61%. Furthermore, there is growing evidence that despite recovery from the acute injury, these infants are at risk for developing hypertension and chronic kidney disease later in life. Emphasis on improving our capability to detect renal insult and injury early, before renal failure occurs, and identification of novel therapeutic agents to prevent and treat acute kidney injury may impact mortality and morbidity. This review focuses on our current knowledge of acute kidney injury in the newborn, approaches to investigating and managing this complication and what future trends in this field may bring. PMID:25088261

  8. Pros and cons of recruitment maneuvers in acute lung injury and acute respiratory distress syndrome.

    PubMed

    Rocco, Patricia R M; Pelosi, Paolo; de Abreu, Marcelo Gama

    2010-08-01

    In patients with acute lung injury and acute respiratory distress syndrome, a protective mechanical ventilation strategy characterized by low tidal volumes has been associated with reduced mortality. However, such a strategy may result in alveolar collapse, leading to cyclic opening and closing of atelectatic alveoli and distal airways. Thus, recruitment maneuvers (RMs) have been used to open up collapsed lungs, while adequate positive end-expiratory pressure (PEEP) levels may counteract alveolar derecruitment during low tidal volume ventilation, improving respiratory function and minimizing ventilator-associated lung injury. Nevertheless, considerable uncertainty remains regarding the appropriateness of RMs. The most commonly used RM is conventional sustained inflation, associated with respiratory and cardiovascular side effects, which may be minimized by newly proposed strategies: prolonged or incremental PEEP elevation; pressure-controlled ventilation with fixed PEEP and increased driving pressure; pressure-controlled ventilation applied with escalating PEEP and constant driving pressure; and long and slow increase in pressure. The efficiency of RMs may be affected by different factors, including the nature and extent of lung injury, capability of increasing inspiratory transpulmonary pressures, patient positioning and cardiac preload. Current evidence suggests that RMs can be used before setting PEEP, after ventilator circuit disconnection or as a rescue maneuver to overcome severe hypoxemia; however, their routine use does not seem to be justified at present. The development of new lung recruitment strategies that have fewer hemodynamic and biological effects on the lungs, as well as randomized clinical trials analyzing the impact of RMs on morbidity and mortality of acute lung injury/acute respiratory distress syndrome patients, are warranted. PMID:20658909

  9. Risk Factors and Outcomes of Acute Kidney Injury in Patients With Acute Liver Failure

    PubMed Central

    Tujios, Shannan R.; Hynan, Linda S.; Vazquez, Miguel A.; Larson, Anne M.; Seremba, Emmanuel; Sanders, Corron M.; Lee, William M.

    2016-01-01

    BACKGROUND & AIMS Patients with acute liver failure (ALF) frequently develop renal dysfunction, yet its overall incidence and outcomes have not been fully assessed. We investigated the incidence of acute kidney injury (AKI) among patients with ALF, using defined criteria to identify risk factors and to evaluate its effect on overall outcomes. METHODS We performed a retrospective review of data from 1604 patients enrolled in the Acute Liver Failure Study Group, from 1998 through 2010. Patients were classified by the Acute Kidney Injury Network criteria, as well as for etiology of liver failure (acetaminophen-based, ischemic, and all others). RESULTS Seventy percent of patients with ALF developed AKI, and 30% received renal replacement therapy (RRT). Patients with severe AKI had higher international normalized ratio values than those without renal dysfunction (P < .001), and a higher proportion had advanced-grade coma (coma grades 3 or 4; P < .001) or presented with hypotension requiring vasopressor therapy (P < .001). A greater proportion of patients with acetaminophen-induced ALF had severe kidney injury than of patients with other etiologies of ALF; 34% required RRT, compared with 25% of patients with ALF not associated with acetaminophen or ischemia (P < .002). Of the patients with ALF who were alive at 3 weeks after study entry, significantly fewer with AKI survived for 1 year. Although AKI reduced the overall survival time, more than 50% of patients with acetaminophen-associated or ischemic ALF survived without liver transplantation (even with RRT), compared with 19% of patients with ALF attribute to other causes (P < .001). Only 4% of patients requiring RRT became dependent on dialysis. CONCLUSIONS Based on a retrospective analysis of data from more than 1600 patients, AKI is common in patients with ALF and affects short- and long-term outcomes, but rarely results in chronic kidney disease. Acetaminophen-induced kidney injury is frequent, but patients have

  10. Liver autophagy in anorexia nervosa and acute liver injury.

    PubMed

    Kheloufi, Marouane; Boulanger, Chantal M; Durand, François; Rautou, Pierre-Emmanuel

    2014-01-01

    Autophagy, a lysosomal catabolic pathway for long-lived proteins and damaged organelles, is crucial for cell homeostasis, and survival under stressful conditions. During starvation, autophagy is induced in numerous organisms ranging from yeast to mammals, and promotes survival by supplying nutrients and energy. In the early neonatal period, when transplacental nutrients supply is interrupted, starvation-induced autophagy is crucial for neonates' survival. In adult animals, autophagy provides amino acids and participates in glucose metabolism following starvation. In patients with anorexia nervosa, autophagy appears initially protective, allowing cells to copes with nutrient deprivation. However, when starvation is critically prolonged and when body mass index reaches 13 kg/m(2) or lower, acute liver insufficiency occurs with features of autophagic cell death, which can be observed by electron microscopy analysis of liver biopsy samples. In acetaminophen overdose, a classic cause of severe liver injury, autophagy is induced as a protective mechanism. Pharmacological enhancement of autophagy protects against acetaminophen-induced necrosis. Autophagy is also activated as a rescue mechanism in response to Efavirenz-induced mitochondrial dysfunction. However, Efavirenz overdose blocks autophagy leading to liver cell death. In conclusion, in acute liver injury, autophagy appears as a protective mechanism that can be however blocked or overwhelmed. PMID:25250330

  11. Adrenal insufficiency presenting as hypercalcemia and acute kidney injury

    PubMed Central

    Ahn, Seung Won; Kim, Tong Yoon; Lee, Sangmin; Jeong, Jeong Yeon; Shim, Hojoon; Han, Yu min; Choi, Kyu Eun; Shin, Seok Joon; Yoon, Hye Eun

    2016-01-01

    Adrenal insufficiency is an uncommon cause of hypercalcemia and not easily considered as an etiology of adrenal insufficiency in clinical practice, as not all cases of adrenal insufficiency manifest as hypercalcemia. We report a case of secondary adrenal insufficiency presenting as hypercalcemia and acute kidney injury in a 66-year-old female. The patient was admitted to the emergency department with general weakness and poor oral intake. Hypercalcemia (11.5 mg/dL) and moderate renal dysfunction (serum creatinine 4.9 mg/dL) were shown in her initial laboratory findings. Studies for malignancy and hyperparathyroidism showed negative results. Basal cortisol and adrenocorticotropic hormone levels and adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency. With the administration of oral hydrocortisone, hypercalcemia was dramatically resolved within 3 days. This case shows that adrenal insufficiency may manifest as hypercalcemia and acute kidney injury, which implicates that adrenal insufficiency should be considered a cause of hypercalcemia in clinical practice. PMID:27536162

  12. Preemptive mechanical ventilation can block progressive acute lung injury

    PubMed Central

    Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

    2016-01-01

    Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS. PMID:26855896

  13. Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention

    PubMed Central

    Faga, Teresa; Pisani, Antonio; Michael, Ashour

    2014-01-01

    It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24–72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. PMID:25197639

  14. Liver Autophagy in Anorexia Nervosa and Acute Liver Injury

    PubMed Central

    Kheloufi, Marouane; Boulanger, Chantal M.; Durand, François

    2014-01-01

    Autophagy, a lysosomal catabolic pathway for long-lived proteins and damaged organelles, is crucial for cell homeostasis, and survival under stressful conditions. During starvation, autophagy is induced in numerous organisms ranging from yeast to mammals, and promotes survival by supplying nutrients and energy. In the early neonatal period, when transplacental nutrients supply is interrupted, starvation-induced autophagy is crucial for neonates' survival. In adult animals, autophagy provides amino acids and participates in glucose metabolism following starvation. In patients with anorexia nervosa, autophagy appears initially protective, allowing cells to copes with nutrient deprivation. However, when starvation is critically prolonged and when body mass index reaches 13 kg/m2 or lower, acute liver insufficiency occurs with features of autophagic cell death, which can be observed by electron microscopy analysis of liver biopsy samples. In acetaminophen overdose, a classic cause of severe liver injury, autophagy is induced as a protective mechanism. Pharmacological enhancement of autophagy protects against acetaminophen-induced necrosis. Autophagy is also activated as a rescue mechanism in response to Efavirenz-induced mitochondrial dysfunction. However, Efavirenz overdose blocks autophagy leading to liver cell death. In conclusion, in acute liver injury, autophagy appears as a protective mechanism that can be however blocked or overwhelmed. PMID:25250330

  15. Preemptive mechanical ventilation can block progressive acute lung injury.

    PubMed

    Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

    2016-02-01

    Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS. PMID:26855896

  16. Acute kidney injury by radiographic contrast media: pathogenesis and prevention.

    PubMed

    Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Michael, Ashour

    2014-01-01

    It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24-72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. PMID:25197639

  17. [Role of computed tomography in the diagnosis of acute lung injury/acute respiratory distress syndrome].

    PubMed

    Mazzei, Maria Antonietta; Guerrini, Susanna; Cioffi Squitieri, Nevada; Franchi, Federico; Volterrani, Luca; Genovese, Eugenio Annibale; Macarini, Luca

    2012-11-01

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a complex pulmonary pathology with high mortality rates, manifesting over a wide range of severity. Clinical diagnosis relies on the following 4 criteria stated by the American-European Consensus Conference: acute onset of impaired gas exchange, severe hypoxemia defined as a PaO2 to FiO2 ratio <300 (PaO2 in mmHg), bilateral diffuse infiltration on chest X-ray; pulmonary artery wedge pressure of ≤18 mmHg to rule out cardiogenic causes of pulmonary edema. The aim of this study was to determine the usefulness of CT in the diagnosis and management of this condition. PMID:23096732

  18. Immune Mechanisms and Novel Pharmacological Therapies of Acute Kidney Injury

    PubMed Central

    Bajwa, Amandeep; Kinsey, Gilbert R.; Okusa, Mark D.

    2010-01-01

    Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and both innate and adaptive immunity contribute to the pathogenesis. Kidney resident cells promote inflammation after IRI by increasing endothelial cell adhesion molecule expression and vascular permeability. Kidney epithelial cells bind complement and express tolllike receptors and resident and infiltrating cells produce cytokines/chemokines. Early activation of kidney dendritic cells (DCs) initiates a cascade of events leading to accumulation of interferon-γ-producing neutrophils, infiltrating macrophages, CD4+ T cells, B cells and invariant natural killer T (NKT) cells. Recent studies from our laboratory now implicate the IL23/IL17 pathway in kidney IRI. Following the initial early phase of inflammation, the late phase involves infiltration of anti-inflammatory cells including regulatory T cells, alternatively activated macrophages and stem cells leading to attenuation of inflammation and initiation of repair. Based upon these immune mechanisms of injury, recent studies hold promise for novel drug therapies. These pharmacological agents have been shown to reduce inflammation or cytotoxicity in rodent models of AKI and some show early promise in clinical trials. This review summarizes recent advances to further our understanding of the immune mechanisms of AKI and potential pharmacological therapies. PMID:19715538

  19. Vitamin D deficiency aggravates ischemic acute kidney injury in rats

    PubMed Central

    de Bragança, Ana Carolina; Volpini, Rildo A; Canale, Daniele; Gonçalves, Janaína G; Shimizu, Maria Heloisa M; Sanches, Talita R; Seguro, Antonio C; Andrade, Lúcia

    2015-01-01

    Vitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which activates cell cycle inhibitors, including p21, a cyclin-dependent kinase inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent immunomodulator with antiproliferative effects. In this study, we assess the impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were euthanized; blood, urine, and kidney tissue samples were collected. Compared with IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration rate, greater urinary protein excretion, a higher kidney/body weight ratio and lower renal aquaporin 2 expression, as well as greater morphological damage, characterized by increased interstitial area and tubular necrosis. Our results suggest that the severity of tubular damage in IRI may be associated with downregulation of vitamin D receptors and p21. VDD increases renal inflammation, cell proliferation and cell injury in ischemic AKI. PMID:25780095

  20. Novel Biomarkers of Acute Kidney Injury After Contrast Coronary Angiography.

    PubMed

    Connolly, M; McEneaney, D; Menown, Ian; Morgan, N; Harbinson, M

    2015-01-01

    Acute kidney injury (AKI), defined as a rise in serum creatinine of greater than 25% from baseline measured at 48 hours after renal insult, may follow iodinated contrast coronary angiography. Termed contrast-induced nephropathy, it can result in considerable morbidity and mortality. Measurement of serum creatinine as a functional biomarker of glomerular filtration rate is widely used for detection of AKI, but it lacks sensitivity for the early diagnosis of AKI (typically rising 24 hours after functional loss) and, as a solely functional marker of glomerular filtration rate, is unable to differentiate among the various causes of AKI. These intrinsic limitations to creatinine measurement and the recognition that improved clinical outcomes are linked to a more timely diagnosis of AKI, has led investigators to search for novel biomarkers of "early" kidney injury. Several studies have investigated the utility of renal injury biomarkers in a variety of clinical settings including angiography/percutaneous coronary intervention, coronary artery bypass graft surgery, sepsis in intensive care patients, and pediatric cardiac surgery. In this article, we discuss the use of iodinated contrast for coronary procedures and the risk factors for contrast-induced nephropathy, followed by a review the potential diagnostic utility of several novel biomarkers of early AKI in the clinical settings of coronary angiography/percutaneous coronary intervention. In particular, we discuss neutrophil gelatinase associated lipocalin in depth. If validated, such biomarkers would facilitate earlier AKI diagnosis and improve clinical outcomes. PMID:25699983

  1. Comparison of stem cell therapies for acute kidney injury

    PubMed Central

    Barnes, Carol J; Distaso, Casey T; Spitz, Kristin M; Verdun, Valerie A; Haramati, Aviad

    2016-01-01

    Acute kidney injury (AKI) is the rapid onset of decreased kidney function that ultimately increases mortality and morbidity. Stem cell research is a promising avenue for curative and preventative therapies of kidney injury, however, there are many types of stem cells under investigation. Currently there is no research to compare the value of one stem cell method over another. Induced pluripotent stem cells (iPSCs) and spermatogonial stem cells (SSCs) have been shown to differentiate into renal cells, though further clinical research is needed to fully explore potential therapeutic strategies. Mesenchymal stem cells (MSCs) have long been investigated in the preclinical setting and have recently been successful in Phase I clinical trials. MSCs may represent a promising new therapeutic approach to treat AKI as they demonstrate renoprotective effects post-injury via the secretion of promitotic, anti-apoptotic, anti-inflammatory, and immunomodulatory factors. Given the most current research, MSCs appear to offer a promising course of treatment for AKI. PMID:27335697

  2. Microglia: Dismantling and rebuilding circuits after acute neurological injury

    PubMed Central

    Ziebell, Jenna M.; Adelson, P. David; Lifshitz, Jonathan

    2014-01-01

    The brain is comprised of neurons and its support system including astrocytes, glial cells and microglia, thereby forming neurovascular units. Neurons require support from glial cells to establish and maintain functional circuits, but microglia are often overlooked. Microglia function as the immune cell of the central nervous system, acting to monitor the microenvironment for changes in signaling, pathogens and injury. More recently, other functional roles for microglia within the healthy brain have been identified, including regulating synapse formation, elimination and function. This review aims to highlight and discuss these alternate microglial roles in the healthy and in contrast, diseased brain with a focus on two acute neurological diseases, traumatic brain injury and epilepsy. In these conditions, microglial roles in synaptic stripping and stabilization as part of neuronal:glial interactions may position them as mediators of the transition between injury-induced circuit dismantling and subsequent reorganization. Increased understanding of microglia roles could identify therapeutic targets to mitigate the consequences of neurological disease. PMID:24733573

  3. Acute kidney injury: from clinical to molecular diagnosis.

    PubMed

    Ronco, Claudio

    2016-01-01

    The RIFLE classification was introduced in 2004 to describe the presence of acute kidney injury (AKI) and to define its clinical stage, based upon the serum creatinine level and urine output. The same criteria, although slightly modified, are used in the other scoring systems AKIN and KDIGO. Mortality and morbidity remain high in AKI, suggesting that current diagnostic methods are suboptimal, poorly accurate, and often timely inadequate in detecting the presence of early kidney injury. Conversely, a growing body of evidence indicates that new AKI biomarkers can be used to both rule out AKI and to assess high-risk conditions or the presence of subclinical forms. Neutrophil gelatinase-associated lipocalin or cell cycle arrest biomarkers seem to be sensitive and specific enough to be used in conjunction with existing markers of AKI for better classifying renal injury as well as dysfunction. Improvements in diagnosis, risk identification, stratification, prognosis, and therapeutic monitoring may improve prevention and protection from organ damage and help to identify patients at risk, allowing individualized therapy. In this view, we may say that AKI diagnosis has finally moved from clinical to molecular level with potential benefits for the patients because similar progress has been shown in other disciplines. PMID:27384344

  4. Acetaminophen-induced acute liver injury in mice.

    PubMed

    Mossanen, J C; Tacke, F

    2015-04-01

    The induction of acute hepatic damage by acetaminophen (N-acetyl-p-aminophenol [APAP]), also termed paracetamol, is one of the most commonly used experimental models of acute liver injury in mice. The specific values of this model are the highly reproducible, dose-dependent hepatotoxicity of APAP and its outstanding translational importance, because acetaminophen overdose is one of the most frequent reasons for acute liver failure (ALF) in humans. However, preparation of concentrated APAP working solutions, application routes, fasting period and variability due to sex, genetic background or barrier environment represent important considerations to be taken into account before implementing this model. This standard operating procedure (SOP) provides a detailed protocol for APAP preparation and application in mice, aimed at facilitating comparability between research groups as well as minimizing animal numbers and distress. The mouse model of acetaminophen poisoning therefore helps to unravel the pathogenesis of APAP-induced toxicity or subsequent immune responses in order to explore new therapeutic interventions for improving the prognosis of ALF in patients. PMID:25835736

  5. Pathophysiology and Clinical Work-Up of Acute Kidney Injury.

    PubMed

    Meola, Mario; Nalesso, Federico; Petrucci, Ilaria; Samoni, Sara; Ronco, Claudio

    2016-01-01

    Acute kidney injury (AKI), also known in the past as acute renal failure, is a syndrome characterized by the rapid loss of kidney excretory function. It is usually diagnosed by the accumulation of end products of nitrogen metabolism (urea and creatinine) or decreased urine output or both. AKI is the clinical consequence of several disorders that acutely affect the kidney, causing electrolytes and acid-base imbalance, hyperhydration and loss of depurative function. AKI is common in critical care patients in whom it is often secondary to extrarenal events. No specific therapies can attenuate AKI or accelerate renal function recovery; thus, the only treatment is supportive. New diagnostic techniques such as renal biomarkers might improve early diagnosis. Also ultrasonography helps nephrologists in AKI diagnosis, in order to describe and follow kidney alterations and find possible causes of AKI. Renal replacement therapy is a life-saving treatment if AKI is severe. If patients survive to AKI, and did not have previous chronic kidney disease (CKD), they typically recover to dialysis independence. However, evidence suggests that patients who have had AKI are at increased risk of subsequent CKD. PMID:27169469

  6. Psychiatric Disease and Post-Acute Traumatic Brain Injury.

    PubMed

    Zgaljardic, Dennis J; Seale, Gary S; Schaefer, Lynn A; Temple, Richard O; Foreman, Jack; Elliott, Timothy R

    2015-12-01

    Psychiatric disorders are common following traumatic brain injury (TBI) and can include depression, anxiety, and psychosis, as well as other maladaptive behaviors and personality changes. The epidemiologic data of psychiatric disorders post-TBI vary widely, although the incidence and prevalence rates typically are higher than in the general population. Although the experience of psychiatric symptoms may be temporary and may resolve in the acute period, many patients with TBI can experience psychopathology that is persistent or that develops in the post-acute period. Long-term psychiatric disorder, along with cognitive and physical sequelae and greater risk for substance use disorders, can pose a number of life-long challenges for patients and their caregivers, as they can interfere with participation in rehabilitation as well as limit functional independence in the community. The current review of the literature considers the common psychiatric problems affecting individuals with TBI in the post-acute period, including personality changes, psychosis, executive dysfunction, depression, anxiety, and substance misuse. Although treatment considerations (pharmacological and nonpharmacological) are referred to, an extensive description of such protocols is beyond the scope of the current review. The impact of persistent psychiatric symptoms on perceived caregiver burden and distress is also discussed. PMID:25629222

  7. Acute Kidney Injury in Patients with Acute Lung Injury: Impact of Fluid Accumulation on Classification of Acute Kidney Injury and Associated Outcomes

    PubMed Central

    Liu, Kathleen D.; Thompson, B. Taylor; Ancukiewicz, Marek; Steingrub, Jay S.; Douglas, Ivor S.; Matthay, Michael A.; Wright, Patrick; Peterson, Michael W.; Rock, Peter; Hyzy, Robert C.; Anzueto, Antonio; Truwit, Jonathon D.

    2011-01-01

    Objective It has been suggested that fluid accumulation may delay recognition of acute kidney injury (AKI). We sought to determine the impact of fluid balance on the incidence of non-dialysis requiring AKI in patients with acute lung injury and to describe associated outcomes, including mortality. Design Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative versus liberal fluid management and of management guided by a central venous versus pulmonary artery catheter. Setting and Patients 1000 patients at ARDS Network hospitals. Measurements and Main Results The incidence of AKI, defined as an absolute rise in creatinine of ≥ 0.3 mg/dL or a relative change of > 50% over 48 hours, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of AKI before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57 versus 51%, p = 0.04). After adjustment for fluid balance, the incidence of AKI was greater in those managed with the liberal fluid protocol (66 versus 58%, p = 0.007). Patients who met AKI criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet AKI criteria both before and after adjustment for fluid balance (31 versus 12%, p < 0.001) and those who had AKI before but not after adjustment for fluid balance (31 versus 11%, p = 0.005). The mortality of those patients meeting AKI criteria after but not before adjustment for fluid balance was similar to patients with AKI both before and after adjustment for fluid balance (31% versus 38%, p = 0.18). Conclusions Fluid management influences serum creatinine and therefore the diagnosis of AKI using creatinine-based definitions. Patients with “unrecognized” AKI that is identified after adjusting for positive fluid balance have high mortality rates, and patients who have AKI before but not after

  8. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    PubMed

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration. PMID:25500295

  9. Histone lysine crotonylation during acute kidney injury in mice

    PubMed Central

    Ruiz-Andres, Olga; Sanchez-Niño, Maria Dolores; Cannata-Ortiz, Pablo; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belen

    2016-01-01

    ABSTRACT Acute kidney injury (AKI) is a potentially lethal condition for which no therapy is available beyond replacement of renal function. Post-translational histone modifications modulate gene expression and kidney injury. Histone crotonylation is a recently described post-translational modification. We hypothesized that histone crotonylation might modulate kidney injury. Histone crotonylation was studied in cultured murine proximal tubular cells and in kidneys from mice with AKI induced by folic acid or cisplatin. Histone lysine crotonylation was observed in tubular cells from healthy murine and human kidney tissue. Kidney tissue histone crotonylation increased during AKI. This was reproduced by exposure to the protein TWEAK in cultured tubular cells. Specifically, ChIP-seq revealed enrichment of histone crotonylation at the genes encoding the mitochondrial biogenesis regulator PGC-1α and the sirtuin-3 decrotonylase in both TWEAK-stimulated tubular cells and in AKI kidney tissue. To assess the role of crotonylation in kidney injury, crotonate was used to increase histone crotonylation in cultured tubular cells or in the kidneys in vivo. Crotonate increased the expression of PGC-1α and sirtuin-3, and decreased CCL2 expression in cultured tubular cells and healthy kidneys. Systemic crotonate administration protected from experimental AKI, preventing the decrease in renal function and in kidney PGC-1α and sirtuin-3 levels as well as the increase in CCL2 expression. For the first time, we have identified factors such as cell stress and crotonate availability that increase histone crotonylation in vivo. Overall, increasing histone crotonylation might have a beneficial effect on AKI. This is the first observation of the in vivo potential of the therapeutic manipulation of histone crotonylation in a disease state. PMID:27125278

  10. Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury

    PubMed Central

    Lee, Sang-Min; McLaughlin, Joseph N.; Frederick, Daniel R.; Zhu, Lin; Thambiayya, Kalidasan; Wasserloos, Karla J.; Kaminski, Iris; Pearce, Linda L.; Peterson, Jim; Li, Jin; Latoche, Joseph D.; Peck Palmer, Octavia M.; Stolz, Donna Beer; Fattman, Cheryl L.; Alcorn, John F.; Oury, Tim D.; Angus, Derek C.; Pitt, Bruce R.

    2013-01-01

    Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury. PMID:23275622

  11. Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

    PubMed Central

    Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

    2013-01-01

    ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

  12. An unusual case of reversible acute kidney injury due to chlorine dioxide poisoning.

    PubMed

    Bathina, Gangadhar; Yadla, Manjusha; Burri, Srikanth; Enganti, Rama; Prasad Ch, Rajendra; Deshpande, Pradeep; Ch, Ramesh; Prayaga, Aruna; Uppin, Megha

    2013-09-01

    Chlorine dioxide is a commonly used water disinfectant. Toxicity of chlorine dioxide and its metabolites is rare. In experimental studies, it was shown that acute and chronic toxicity were associated with insignificant hematological changes. Acute kidney injury due to chlorine dioxide was not reported. Two cases of renal toxicity due to its metabolites, chlorate and chlorite were reported. Herein, we report a case of chlorine dioxide poisoning presenting with acute kidney injury. PMID:23902291

  13. Acute Kidney Injury Associated With Vancomycin When Laxity Leads to Injury and Findings on Kidney Biopsy.

    PubMed

    Katikaneni, Madhavi; Lwin, Lin; Villanueva, Hugo; Yoo, Jinil

    2016-01-01

    The issue of vancomycin-induced acute kidney injury (AKI) has resurged with the use of intravenous vancomycin as a first-line antibiotic, often for prolonged periods of time for the management of serious methicillin-resistant Staphylococcus aureus infections, and with a higher recommended trough level (15-20 μg/mL). We have observed 3 patients on intravenous vancomycin who developed very high trough levels (>40 μg/mL) and severe (stage 3) AKI. Those 3 patients underwent kidney biopsy for unresolving AKI, which revealed findings compatible with acute tubular necrosis. The first patient initially developed asymptomatic acute interstitial nephritis because of a concomitant antibiotic that caused worsening of kidney function, and the dose of vancomycin was not properly adjusted while staying at the nursing home. The second was an emaciated patient (BMI, 14) whose serum creatinine level was a deceptive marker of kidney function for the proper dosing of vancomycin, resulting in a toxic level. The third patient developed vancomycin-related AKI on an initially high therapeutic level, which then contributed to further rising in vancomycin level and subsequently causing severe AKI. One patient required hemodialysis, but all 3 patients ultimately recovered their kidney function significantly. A regular monitoring (preferably twice weekly) of serum creatinine and vancomycin trough level is advisable to minimize vancomycin-associated AKI, primarily acute tubular necrosis, for patients requiring prolonged administration of vancomycin (>2 weeks) on the currently recommended higher therapeutic trough levels (>15 μg/mL). PMID:26035034

  14. Biomarkers in Acute Lung Injury – Marking Forward Progress

    PubMed Central

    Barnett, Nicolas; Ware, Lorraine B.

    2011-01-01

    In this article we review the ‘state of the art’ with regards to biomarkers for prediction, diagnosis and prognosis in acute lung injury (ALI). We begin by defining biomarkers and the goals of biomarker research in ALI including their ability to define more homogenous populations for recruitment into trials of novel therapies as well as to identify important biological pathways in the pathogenesis of ALI. Progress along four general routes is then examined. First the results of wide-ranging existing protein biomarkers are reported. Secondly, we describe newer biomarkers awaiting or with strong potential for validation. Thirdly, we report progress in the fields of genomics and proteomics. Finally given the complexity and number of potential biomarkers, we examine the results of combining clinical predictors with protein and other biomarkers to produce better prognostic and diagnostic indices. PMID:21742222

  15. Pathogenesis of Acute Kidney Injury: Foundation for Clinical Practice

    PubMed Central

    Kinsey, Gilbert R.; Okusa, Mark D.

    2011-01-01

    The pathogenesis of acute kidney injury (AKI) is complex, involving factors such as vasoconstriction, leukostasis, vascular congestion, cell death, and abnormal immune modulators and growth factors. Many targeted clinical therapies have failed, are inconclusive, or have yet to be tested. Given the complexity of the pathogenesis of AKI, it may be naïve to expect one therapeutic intervention would have success. Some examples of detrimental processes that can be blocked in pre-clinical models to improve kidney function and survival are apoptotic cell death in tubular epithelial cells, complement-mediated immune system activation, and impairment of cellular homeostasis and metabolism. Modalities with potential to reduce morbidity and mortality in AKI include vasodilators, growth factors, anti-inflammatory agents, and cell-based therapies. Pharmacological agents that target these diverse pathways are being used clinically for other indications. Using combinatorial approaches in future clinical trials may improve our ability to prevent and treat AKI. PMID:21530035

  16. Acute kidney injury after massive attack of Africanised bees.

    PubMed

    Bridi, Ramaiane A; Balbi, Andre Luis; Neves, Precil M; Ponce, Daniela

    2014-01-01

    Acute kidney injury (AKI) is a well-documented complication of massive attack by Africanised bees and can be observed 48-72 h after the accident. We report a case of Africanised bees attack followed by severe and lethal AKI. A 56-year-old man was admitted to emergency department after a massive attack of Africanised bees (>1000 bee stings). He was unconscious, presenting with hypotension and tachycardia. Mechanical ventilation, volume expansion and care for anaphylaxis were instituted. The patient was transferred to the intensive care unit (ICU) and after 48 h he developed rhabdomyolysis, oliguria, increased creatinine levels, hyperkalaemia and refractory acidosis. A diagnosis of AKI secondary to rhabdomyolysis and shock was made. The patient was treated with a prolonged course of haemodialysis. However, he progressed to refractory shock and died 5 days after admission. PMID:24618864

  17. Necroptosis in acute kidney injury: a shedding light

    PubMed Central

    Wang, S; Zhang, C; Hu, L; Yang, C

    2016-01-01

    Acute kidney injury (AKI) is a common and severe clinical condition with a heavy healthy burden around the world. In spite of supportive therapies, the mortality associated with AKI remains high. Our limited understanding of the complex cell death mechanism in the process of AKI impedes the development of desirable therapeutics. Necroptosis is a recently identified novel form of cell death contributing to numerable diseases and tissue damages. Increasing evidence has suggested that necroptosis has an important role in the pathogenesis of various types of AKI. Therefore, we present here the signaling pathways and main regulators of necroptosis that are potential candidate for therapeutic strategies. Moreover, we emphasize on the potential role and corresponding mechanisms of necroptosis in AKI based on recent advances, and also discuss the possible therapeutic regimens based on manipulating necroptosis. Taken together, the progress in this field sheds new light into the prevention and management of AKI in clinical practice. PMID:26938298

  18. Pyelonephritis and obstructive uropathy: a case of acute kidney injury.

    PubMed

    Ashmore, Adam Edward; Thompson, Christopher James

    2016-01-01

    We present a case of a man in his late 50s with a history of metastatic prostate carcinoma requiring bilateral ureteric stenting. He was admitted with increasing confusion and lethargy. He was diagnosed with sepsis and an acute kidney injury (AKI). Clinical suspicions of an obstructive component to his AKI were not confirmed by an ultrasound scan, which showed a unilateral hydronephrosis unchanged from a scan 1 month previously. A nephrostomy was performed, and frank pus aspirated. The patient's clinical state improved steadily thereafter. Patients who are dehydrated, or who have suffered from malignant or fibrotic processes affecting the retroperitoneum, may present with urinary obstruction without a corresponding increase in urinary tract dilation. Additionally, there must be a suspicion of pyonephrosis in a symptomatic patient with known hydronephrosis. Clinicians should be aware that clinical suspicions of urinary obstruction not demonstrated on ultrasound scanning require further investigation. PMID:26733429

  19. Renoprotective approaches and strategies in acute kidney injury.

    PubMed

    Yang, Yuan; Song, Meifang; Liu, Yu; Liu, Hong; Sun, Lin; Peng, Youming; Liu, Fuyou; Venkatachalam, Manjeri A; Dong, Zheng

    2016-07-01

    Acute kidney injury (AKI) is a major renal disease associated with high mortality rate and increasing prevalence. Decades of research have suggested numerous chemical and biological agents with beneficial effects in AKI. In addition, cell therapy and molecular targeting have been explored for reducing kidney tissue damage and promoting kidney repair or recovery from AKI. Mechanistically, these approaches may mitigate oxidative stress, inflammation, cell death, and mitochondrial and other organellar damage, or activate cytoprotective mechanisms such as autophagy and pro-survival factors. However, none of these findings has been successfully translated into clinical treatment of AKI. In this review, we analyze these findings and propose experimental strategies for the identification of renoprotective agents or methods with clinical potential. Moreover, we propose the consideration of combination therapy by targeting multiple targets in AKI. PMID:27108948

  20. Mitochondria: a therapeutic target in acute kidney injury.

    PubMed

    Ishimoto, Yu; Inagi, Reiko

    2016-07-01

    Acute kidney injury (AKI) is a common clinical entity that is associated with high mortality and morbidity. It is a risk factor for the development and progression of chronic kidney disease. Presently, no effective treatment for AKI is available, and novel therapeutic approaches are desperately needed. Accumulating evidence highlights mitochondrial dysfunction as an important factor in the pathogenesis of AKI. Recent advances in our understanding of the molecules involved in mitochondrial biogenesis, fusion/fission, mitophagy and their pathophysiological roles will lead to the development of drugs that target mitochondria for the treatment of various diseases, including AKI. In this review, we summarize current knowledge of the contribution of mitochondria-related pathophysiology in AKI and the prospective benefits of mitochondria-targeting therapeutic approaches against AKI. PMID:26333547

  1. Recurrent acute kidney injury associated with metastatic bronchial carcinoid.

    PubMed

    Barton, James C; Barton, J Clayborn; Bertoli, Luigi F

    2012-01-01

    Acute kidney injury (AKI) is a rare complication of carcinoid syndrome. A 61-year-old man developed carcinoid syndrome 51 months after pneumonectomy for bronchial carcinoid, and 8 episodes of AKI 101 to 118 months after pneumonectomy. Serum chromogranin A and urine 5-hydroxyindoleacetic acid levels were elevated for more than 1 year before AKI occurred. Each episode was characterized by flushing, facial edema, mild diarrhea, necrosis of hepatic metastatic nodules, mild oliguria, hyponatremia, acidosis, hypokalemia, hypomagnesemia and hyperphosphatemia. He did not have elevated urine sodium levels or osmolality, hypotension or hypertension. Plasma levels of dopamine, epinephrine and norepinephrine, measured during a single episode, were markedly elevated. Serum creatinine levels returned to normal after most episodes. Hyponatremia persisted but was more severe during AKI. Elevated plasma levels of vasoactive substances other than 5-hydroxytryptamine, perhaps dopamine or other catecholamines, could explain recurrent AKI. The natriuretic effect of elevated plasma dopamine levels could explain chronic hyponatremia. PMID:22008780

  2. What is the real impact of acute kidney injury?

    PubMed Central

    2014-01-01

    Background Acute kidney injury (AKI) is a common clinical problem. Studies have documented the incidence of AKI in a variety of populations but to date we do not believe the real incidence of AKI has been accurately documented in a district general hospital setting. The aim here was to describe the detected incidence of AKI in a typical general hospital setting in an unselected population, and describe associated short and long-term outcomes. Methods A retrospective observational database study from secondary care in East Kent (adult catchment population of 582,300). All adult patients (18 years or over) admitted between 1st February 2009 and 31st July 2009, were included. Patients receiving chronic renal replacement therapy (RRT), maternity and day case admissions were excluded. AKI was defined by the acute kidney injury network (AKIN) criteria. A time dependent risk analysis with logistic regression and Cox regression was used for the analysis of in-hospital mortality and survival. Results The incidence of AKI in the 6 month period was 15,325 pmp/yr (adults) (69% AKIN1, 18% AKIN2 and 13% AKIN3). In-hospital mortality, length of stay and ITU utilisation all increased with severity of AKI. Patients with AKI had an increase in care on discharge and an increase in hospital readmission within 30 days. Conclusions This data comes closer to the real incidence and outcomes of AKI managed in-hospital than any study published in the literature to date. Fifteen percent of all admissions sustained an episode of AKI with increased subsequent short and long term morbidity and mortality, even in those with AKIN1. This confers an increased burden and cost to the healthcare economy, which can now be quantified. These results will furnish a baseline for quality improvement projects aimed at early identification, improved management, and where possible prevention, of AKI. PMID:24952580

  3. Electronic Medical Record-Based Predictive Model for Acute Kidney Injury in an Acute Care Hospital.

    PubMed

    Laszczyńska, Olga; Severo, Milton; Azevedo, Ana

    2016-01-01

    Patients with acute kidney injury (AKI) are at risk for increased morbidity and mortality. Lack of specific treatment has meant that efforts have focused on early diagnosis and timely treatment. Advanced algorithms for clinical assistance including AKI prediction models have potential to provide accurate risk estimates. In this project, we aim to provide a clinical decision supporting system (CDSS) based on a self-learning predictive model for AKI in patients of an acute care hospital. Data of all in-patient episodes in adults admitted will be analysed using "data mining" techniques to build a prediction model. The subsequent machine-learning process including two algorithms for data stream and concept drift will refine the predictive ability of the model. Simulation studies on the model will be used to quantify the expected impact of several scenarios of change in factors that influence AKI incidence. The proposed dynamic CDSS will apply to future in-hospital AKI surveillance in clinical practice. PMID:27577501

  4. Mitochondrial dysfunction in inherited renal disease and acute kidney injury.

    PubMed

    Emma, Francesco; Montini, Giovanni; Parikh, Samir M; Salviati, Leonardo

    2016-05-01

    Mitochondria are increasingly recognized as key players in genetic and acquired renal diseases. Most mitochondrial cytopathies that cause renal symptoms are characterized by tubular defects, but glomerular, tubulointerstitial and cystic diseases have also been described. For example, defects in coenzyme Q10 (CoQ10) biosynthesis and the mitochondrial DNA 3243 A>G mutation are important causes of focal segmental glomerulosclerosis in children and in adults, respectively. Although they sometimes present with isolated renal findings, mitochondrial diseases are frequently associated with symptoms related to central nervous system and neuromuscular involvement. They can result from mutations in nuclear genes that are inherited according to classic Mendelian rules or from mutations in mitochondrial DNA, which are transmitted according to more complex rules of mitochondrial genetics. Diagnosis of mitochondrial disorders involves clinical characterization of patients in combination with biochemical and genetic analyses. In particular, prompt diagnosis of CoQ10 biosynthesis defects is imperative because of their potentially reversible nature. In acute kidney injury (AKI), mitochondrial dysfunction contributes to the physiopathology of tissue injury, whereas mitochondrial biogenesis has an important role in the recovery of renal function. Potential therapies that target mitochondrial dysfunction or promote mitochondrial regeneration are being developed to limit renal damage during AKI and promote repair of injured tissue. PMID:26804019

  5. Escin attenuates acute lung injury induced by endotoxin in mice.

    PubMed

    Xin, Wenyu; Zhang, Leiming; Fan, Huaying; Jiang, Na; Wang, Tian; Fu, Fenghua

    2011-01-18

    Endotoxin causes multiple organ dysfunctions, including acute lung injury (ALI). The current therapeutic strategies for endotoxemia are designed to neutralize one or more of the inflammatory mediators. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and anti-edematous effects. The aim of this study was to evaluate the effect of escin on ALI induced by endotoxin in mice. ALI was induced by injection of lipopolysaccharide (LPS) intravenously. The mice were given dexamethasone or escin before injection of LPS. The mortality rate was recorded. Tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO) were measured. Pulmonary superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, glutathione (GSH), malondialdehyde (MDA) contents, and myeloperoxidase (MPO) activity were also determined. The expression of glucocorticoid receptor (GR) level was detected by Western blotting. Pretreatment with escin could decrease the mortality rate, attenuate lung injury resulted from LPS, down-regulate the level of the inflammation mediators, including NO, TNF-α, and IL-1β, enhance the endogenous antioxidant capacity, and up-regulating the GR expression in lung. The results suggest that escin may have potent protective effect on the LPS-induced ALI by inhibiting of the inflammatory response, and its mechanism involves in up-regulating the GR and enhancing the endogenous antioxidant capacity. PMID:21040784

  6. Acute kidney injury: Renal disease in the ICU.

    PubMed

    Seller-Pérez, G; Más-Font, S; Pérez-Calvo, C; Villa-Díaz, P; Celaya-López, M; Herrera-Gutiérrez, M E

    2016-01-01

    Acute kidney injury (AKI) in the ICU frequently requires costly supportive therapies, has high morbidity, and its long-term prognosis is not as good as it has been presumed so far. Consequently, AKI generates a significant burden for the healthcare system. The problem is that AKI lacks an effective treatment and the best approach relies on early secondary prevention. Therefore, to facilitate early diagnosis, a broader definition of AKI should be established, and a marker with more sensitivity and early-detection capacity than serum creatinine - the most common marker of AKI - should be identified. Fortunately, new classification systems (RIFLE, AKIN or KDIGO) have been developed to solve these problems, and the discovery of new biomarkers for kidney injury will hopefully change the way we approach renal patients. As a first step, the concept of renal failure has changed from being a "static" disease to being a "dynamic process" that requires continuous evaluation of kidney function adapted to the reality of the ICU patient. PMID:27388683

  7. Endothelial Glycocalyx Damage Is Associated with Leptospirosis Acute Kidney Injury

    PubMed Central

    Libório, Alexandre Braga; Braz, Marcelo Boecker Munoz; Seguro, Antonio Carlos; Meneses, Gdayllon C.; Neves, Fernanda Macedo de Oliveira; Pedrosa, Danielle Carvalho; Cavalcanti, Luciano Pamplona de Góes; Martins, Alice Maria Costa; Daher, Elizabeth de Francesco

    2015-01-01

    Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P < 0.001) and syndecan-1 (73.7 ± 15.9 versus 21.2 ± 7.9 ng/mL, P < 0.001) compared with exposed controls. Patients with leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinase-associated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKI-associated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage. PMID:25624405

  8. Crocin attenuates lipopolysacchride-induced acute lung injury in mice

    PubMed Central

    Wang, Jian; Kuai, Jianke; Luo, Zhonghua; Wang, Wuping; Wang, Lei; Ke, Changkang; Li, Xiaofei; Ni, Yunfeng

    2015-01-01

    Crocin, a representative of carotenoid compounds, exerts a spectrum of activities including radical scavenger, anti-microbial and anti-inflammatory properties. To investigate the protective effect of crocin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg). The mice received intragastric injection of crocin (50 mg/kg) 1 h before LPS administration. Pulmonary histological changes were evaluated by hematoxylineosin stain and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nitric oxide (NO), and myeloperoxidase (MPO) activity were measured by enzymelinked immunosorbent assay. Expression of inducible nitric oxide synthase (iNOS) in lung tissues was determined by Western blot analysis. Crocin pretreatment significantly alleviated the severity of lung injury and inhibited the production of TNF-α and IL-1β in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by crocin pretreatment. Crocin pretreatment also reduced the concentrations of NO in lung tissues. Furthermore, the expression of iNOS was significantly suppressed by crocin pretreatment. Croncin potently protected against LPS-induced ALI and the protective effects of crocin may attribute partly to the suppression of iNOS expression. PMID:26191176

  9. Pharmacotherapy in rehabilitation of post-acute traumatic brain injury.

    PubMed

    Bhatnagar, Saurabha; Iaccarino, Mary Alexis; Zafonte, Ross

    2016-06-01

    There are nearly 1.8 million annual emergency room visits and over 289,000 annual hospitalizations related to traumatic brain injury (TBI). The goal of this review article is to highlight pharmacotherapies that we often use in the clinic that have been shown to benefit various sequelae of TBI. We have decided to focus on sequelae that we commonly encounter in our practice in the post-acute phase after a TBI. These symptoms are hyper-arousal, agitation, hypo-arousal, inattention, slow processing speed, memory impairment, sleep disturbance, depression, headaches, spasticity, and paroxysmal sympathetic hyperactivity. In this review article, the current literature for the pharmacological management of these symptoms are mentioned, including medications that have not had success and some ongoing trials. It is clear that the pharmacological management specific to those with TBI is often based on small studies and that often treatment is based on assumptions of how similar conditions are managed when not relating to TBI. As the body of the literature expands and targeted treatments start to emerge for TBI, the function of pharmacological management will need to be further defined. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26801831

  10. TNFR1-dependent pulmonary apoptosis during ischemic acute kidney injury

    PubMed Central

    White, Laura E.; Santora, Rachel J.; Cui, Yan; Moore, Frederick A.

    2012-01-01

    Despite advancements in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely due to remote organ injury. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that incite a distinct pulmonary proinflammatory and proapoptotic response. Tumor necrosis factor receptor 1 (TNFR1) has been identified as a prominent death receptor activated in the lungs during ischemic AKI. We hypothesized that circulating TNF-α released from the postischemic kidney induces TNFR1-mediated pulmonary apoptosis, and we aimed to elucidate molecular pathways to programmed cell death. Using an established murine model of kidney IRI, we characterized the time course for increased circulatory and pulmonary TNF-α levels and measured concurrent upregulation of pulmonary TNFR1 expression. We then identified TNFR1-dependent pulmonary apoptosis after ischemic AKI using TNFR1−/− mice. Subsequent TNF-α signaling disruption with Etanercept implicated circulatory TNF-α as a key soluble mediator of pulmonary apoptosis and lung microvascular barrier dysfunction during ischemic AKI. We further elucidated pathways of TNFR1-mediated apoptosis with NF-κB (Complex I) and caspase-8 (Complex II) expression and discovered that TNFR1 proapoptotic signaling induces NF-κB activation. Additionally, inhibition of NF-κB (Complex I) resulted in a proapoptotic phenotype, lung barrier leak, and altered cellular flice inhibitory protein signaling independent of caspase-8 (Complex II) activation. Ischemic AKI activates soluble TNF-α and induces TNFR1-dependent pulmonary apoptosis through augmentation of the prosurvival and proapoptotic TNFR1 signaling pathway. Kidney-lung crosstalk after ischemic AKI represents a complex pathological process, yet focusing on specific biological pathways may yield potential future therapeutic targets. PMID:22728466

  11. Neutrophil lipoxygenase metabolism and adhesive function following acute thermal injury.

    PubMed

    Damtew, B; Marino, J A; Fratianne, R B; Spagnuolo, P J

    1993-02-01

    Leukotrienes, especially leukotriene B4, are important modulators of various neutrophil functions including adherence and chemotaxis. In previous work, we demonstrated that neutrophil adherence to extracellular matrixes was diminished in the acute stages of burn injury. In this study, we demonstrated that neutrophil adhesion to human and bovine endothelium in the baseline state and after stimulation with leukotriene B4 is depressed markedly after burn injury. The defect in stimulated adherence to endothelium was not specific to leukotriene B4 because impaired adhesion was observed with n-formyl-methionyl-leucyl-phenylalanine and ionophore A23187 as well. Moreover, the adherence defect correlated with 95% and 81% decreases in the release of leukotriene B4 and 5-hydroxy-(6E,87,117,147)-eicosatetraenoic acid, respectively, from burn PMN treated with A23187. Burn neutrophils also released proportionately more byproducts of leukotriene B4 omega oxidation, particularly 20-COOH-leukotriene B4, than did control neutrophils. When examined 3 1/2 weeks after injury, abnormalities in neutrophil leukotriene B4 generation and the adherence of burn neutrophils had recovered to near normal values. To determine whether the decreased release of leukotriene B4 from burn neutrophils was due to increased degradation or diminished synthesis of leukotriene B4, we examined the degradation of exogenous tritiated leukotriene B4 as well as the production of leukotriene B4 from tritiated arachidonic acid in neutrophils. Burn neutrophils converted significantly greater quantities of tritiated leukotriene B4 to tritiated 20-COOH-leukotriene B4 and synthesized markedly less tritiated leukotriene B4 from tritiated arachidonic acid than did control neutrophils, suggesting that decreased leukotriene B4 release by burn neutrophils was the result of both enhanced degradation and decreased synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8381849

  12. Postpartum acute kidney injury: a review of 99 cases.

    PubMed

    Eswarappa, Mahesh; Madhyastha, P Rakesh; Puri, Sonika; Varma, Vijay; Bhandari, Aneesh; Chennabassappa, Gurudev

    2016-07-01

    Postpartum acute kidney injury (PPAKI) constitutes an important cause of obstetric AKI. It is associated with high maternal and fetal mortality in developing nations. The aim of this study is to survey the etiology and outcomes of PPAKI in a tertiary care Indian hospital. Ninety-nine patients, without prior comorbidities, treated for PPAKI, between 2005-2014 at M.S. Ramaiah Medical College, were included for analysis in this retrospective, observational study. AKI was analyzed in terms of maximal stage of renal injury attained as per RIFLE criteria. Outcomes included requirement for renal replacement therapy (RRT), maternal and fetal outcomes. PPAKI constituted 60% of all obstetric AKI cases. Median maternal age was 23 years and 52% of patients were primigravidas. Mean serum creatinine was 4.1 mg/dL. Failure (33%) and injury (31%) were the major categories as per RIFLE criteria. Thirty-nine percent of cases required RRT. Sepsis, particularly puerperal sepsis, was the leading causes of PPAKI (75% of cases) and maternal mortality (94% of deaths). Maternal and fetal mortality were 19% and 22% respectively. The incidence of cortical necrosis was 10.3%. Three patients required long-term RRT. In conclusion, consistent with other Indian literature, we report a high incidence of PPAKI. We found incremental mortality on moving from "Risk" to "Failure" category of RIFLE. PPAKI was associated with high maternal and fetal mortality with sepsis being the leading cause. Our study highlights the need for provision of better quality of maternal care and fetal monitoring to decrease mortality associated with PPAKI in developing countries. PMID:27319810

  13. Optimizing sedation in patients with acute brain injury.

    PubMed

    Oddo, Mauro; Crippa, Ilaria Alice; Mehta, Sangeeta; Menon, David; Payen, Jean-Francois; Taccone, Fabio Silvio; Citerio, Giuseppe

    2016-01-01

    Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has 'general' indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and 'neuro-specific' indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity. PMID:27145814

  14. Severe physical exertion, oxidative stress, and acute lung injury.

    PubMed

    Shah, Nikunj R; Iqbal, M Bilal; Barlow, Andrew; Bayliss, John

    2011-11-01

    We report the case of a 27-year-old male athlete presenting with severe dyspnoea 24 hours after completing an "Ironman Triathlon." Subsequent chest radiology excluded pulmonary embolus but confirmed an acute lung injury (ALI). Echocardiography corroborated a normal brain natriuretic peptide level by demonstrating good biventricular systolic function with no regional wall motion abnormalities. He recovered well, without requiring ventilatory support, on supplemental oxygen therapy and empirical antibiotics. To date, ALI following severe physical exertion has never been described. Exercise is a form of physiological stress resulting in oxidative stress through generation of reactive oxygen/nitrogen species. In its extreme form, there is potential for an excessive oxidative stress response--one that overwhelms the body's protective antioxidant mechanisms. As our case demonstrated, oxidative stress secondary to severe physical exertion was the most likely factor in the pathogenesis of ALI. Further studies are necessary to explore the pathological consequences of exercise-induced oxidative stress. Although unproven as of yet, further research may be needed to demonstrate if antioxidant therapy can prevent or ameliorate potential life-threatening complications in the acute setting. PMID:22064719

  15. Acute kidney injury in critically ill cancer patients: an update.

    PubMed

    Lameire, Norbert; Vanholder, Raymond; Van Biesen, Wim; Benoit, Dominique

    2016-01-01

    Patients with cancer represent a growing group among actual ICU admissions (up to 20 %). Due to their increased susceptibility to infectious and noninfectious complications related to the underlying cancer itself or its treatment, these patients frequently develop acute kidney injury (AKI). A wide variety of definitions for AKI are still used in the cancer literature, despite existing guidelines on definitions and staging of AKI. Alternative diagnostic investigations such as Cystatin C and urinary biomarkers are discussed briefly. This review summarizes the literature between 2010 and 2015 on epidemiology and prognosis of AKI in this population. Overall, the causes of AKI in the setting of malignancy are similar to those in other clinical settings, including preexisting chronic kidney disease. In addition, nephrotoxicity induced by the anticancer treatments including the more recently introduced targeted therapies is increasingly observed. However, data are sometimes difficult to interpret because they are often presented from the oncological rather than from the nephrological point of view. Because the development of the acute tumor lysis syndrome is one of the major causes of AKI in patients with a high tumor burden or a high cell turnover, the diagnosis, risk factors, and preventive measures of the syndrome will be discussed. Finally, we will briefly discuss renal replacement therapy modalities and the emergence of chronic kidney disease in the growing subgroup of critically ill post-AKI survivors. PMID:27480256

  16. Lithium-Induced Minimal Change Disease and Acute Kidney Injury

    PubMed Central

    Tandon, Parul; Wong, Natalie; Zaltzman, Jeffrey S

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. PMID:26258081

  17. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury.

    PubMed

    Duann, Pu; Lianos, Elias A; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  18. Effect of Thoracentesis on Intubated Patients with Acute Lung Injury.

    PubMed

    Bloom, Matthew B; Serna-Gallegos, Derek; Ault, Mark; Khan, Ahsan; Chung, Rex; Ley, Eric J; Melo, Nicolas; Margulies, Daniel R

    2016-03-01

    Pleural effusions occur frequently in mechanically ventilated patients, but no consensus exists regarding the clinical benefit of effusion drainage. We sought to determine the impact of thoracentesis on gas exchange in patients with differing severities of acute lung injury (ALI). A retrospective analysis was conducted on therapeutic thoracenteses performed on intubated patients in an adult surgical intensive care unit of a tertiary center. Effusions judged by ultrasound to be 400 mL or larger were drained. Subjects were divided into groups based on their initial P:F ratios: normal >300, ALI 200 to 300, and acute respiratory distress syndrome (ARDS) <200. Baseline characteristics, physiologic variables, arterial blood gases, and ventilator settings before and after the intervention were analyzed. The primary end point was the change in measures of oxygenation. Significant improvements in P:F ratios (mean ± SD) were seen only in patients with ARDS (50.4 ± 38.5, P = 0.001) and ALI (90.6 ± 161.7, P = 0.022). Statistically significant improvement was observed in the pO2 (31.1, P = 0.005) and O2 saturation (4.1, P < 0.001) of the ARDS group. The volume of effusion removed did not correlate with changes in individual patient's oxygenation. These data support the role of therapeutic thoracentesis for intubated patients with abnormal P:F ratios. PMID:27099064

  19. Gastric dysreflexia after acute experimental spinal cord injury in rats

    PubMed Central

    Tong, M.; Holmes, G. M.

    2009-01-01

    Gastric reflexes are mediated mainly by vago-vagal reflex circuits in the caudal medulla. Despite the fact that brainstem vago-vagal circuitry remains intact after spinal cord injury (SCI), patients with SCI at the cervical level most often present gastric stasis with an increased risk of reflux and aspiration of gastric contents. Using a miniature strain gauge sutured to the gastric surface; we tested gastric motility and reflexive gastric relaxation following oesophageal distension (oesophageal-gastric relaxation reflex) in animals 3 days after a severe spinal contusion at either the third or ninth thoracic spinal segment (acute T3- or T9 SCI, respectively). Both basal gastric motility and the oesophageal-gastric relaxation reflex were significantly diminished in animals with T3 SCI. Conversely, both basal gastric motility and the oesophageal-gastric relaxation reflex were not significantly reduced in T9 SCI animals compared to controls. The reduced gastric motility and oesophageal-gastric reflex in T3 SCI rats was not ameliorated by celiac sympathectomy. Our results show that gastric stasis following acute SCI is independent of altered spinal sympathetic input to the stomach caudal to the lesion. Our data suggest that SCI may alter the sensitivity of vagal reflex function, perhaps by interrupting ascending spinosolitary input to brainstem vagal nuclei. PMID:19126185

  20. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    PubMed Central

    Duann, Pu; Lianos, Elias A.; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  1. Changing Interdigestive Migrating Motor Complex in Rats under Acute Liver Injury

    PubMed Central

    Zheng, Su-Jun; Xu, Weihong; Zhang, Jianying; Chen, Yu; Duan, Zhongping

    2014-01-01

    Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC) is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created by d-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders. PMID:25544942

  2. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    PubMed Central

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  3. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    NASA Astrophysics Data System (ADS)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-06-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

  4. Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation

    PubMed Central

    Gonçalves-de-Albuquerque, Cassiano Felippe; Silva, Adriana Ribeiro; Burth, Patrícia; Castro-Faria, Mauro Velho; Castro-Faria-Neto, Hugo Caire

    2015-01-01

    Lung injury especially acute respiratory distress syndrome (ARDS) can be triggered by diverse stimuli, including fatty acids and microbes. ARDS affects thousands of people worldwide each year, presenting high mortality rate and having an economic impact. One of the hallmarks of lung injury is edema formation with alveoli flooding. Animal models are used to study lung injury. Oleic acid-induced lung injury is a widely used model resembling the human disease. The oleic acid has been linked to metabolic and inflammatory diseases; here we focus on lung injury. Firstly, we briefly discuss ARDS and secondly we address the mechanisms by which oleic acid triggers lung injury and inflammation. PMID:26640323

  5. Effort test performance in clinical acute brain injury, community brain injury, and epilepsy populations.

    PubMed

    Hampson, Natalie E; Kemp, Steven; Coughlan, Anthony K; Moulin, Chris J A; Bhakta, Bipin B

    2014-01-01

    Effort tests have become commonplace within medico-legal and forensic contexts and their use is rising within clinical settings. It is recognized that some patients may fail effort tests due to cognitive impairment and not because of poor effort. However, investigation of the base rate of failure among clinical populations other than dementia is limited. Forty-seven clinical participants were recruited and comprised three subgroups: acute brain injury (N = 11), community brain injury (N = 20), and intractable epilepsy (N = 16). Base rates of failure on the Word Memory Test (WMT; Green, 2003 ) and six other less well-validated measures were investigated. A significant minority of patients failed effort tests according to standard cutoff scores, particularly patients with severe traumatic brain injury and marked frontal-executive features. The WMT was able to identify failures associated with significant cognitive impairment through the application of profile analysis and/or lowered cutoff levels. Implications for clinical assessment, effort test interpretation, and future research are discussed. PMID:25084843

  6. Brain and behavioral evidence for altered social learning mechanisms among women with assault-related posttraumatic stress disorder.

    PubMed

    Cisler, Josh M; Bush, Keith; Scott Steele, J; Lenow, Jennifer K; Smitherman, Sonet; Kilts, Clinton D

    2015-04-01

    Current neurocircuitry models of PTSD focus on the neural mechanisms that mediate hypervigilance for threat and fear inhibition/extinction learning. Less focus has been directed towards explaining social deficits and heightened risk of revictimization observed among individuals with PTSD related to physical or sexual assault. The purpose of the present study was to foster more comprehensive theoretical models of PTSD by testing the hypothesis that assault-related PTSD is associated with behavioral impairments in a social trust and reciprocity task and corresponding alterations in the neural encoding of social learning mechanisms. Adult women with assault-related PTSD (n = 25) and control women (n = 15) completed a multi-trial trust game outside of the MRI scanner. A subset of these participants (15 with PTSD and 14 controls) also completed a social and non-social reinforcement learning task during 3T fMRI. Brain regions that encoded the computationally modeled parameters of value expectation, prediction error, and volatility (i.e., uncertainty) were defined and compared between groups. The PTSD group demonstrated slower learning rates during the trust game and social prediction errors had a lesser impact on subsequent investment decisions. PTSD was also associated with greater encoding of negative expected social outcomes in perigenual anterior cingulate cortex and bilateral middle frontal gyri, and greater encoding of social prediction errors in the left temporoparietal junction. These data suggest mechanisms of PTSD-related deficits in social functioning and heightened risk for re-victimization in assault victims; however, comorbidity in the PTSD group and the lack of a trauma-exposed control group temper conclusions about PTSD specifically. PMID:25769397

  7. Brain and Behavioral Evidence for Altered Social Learning Mechanisms among Women with Assault-Related Posttraumatic Stress Disorder

    PubMed Central

    Cisler, Josh M.; Bush, Keith; Steele, J. Scott; Lenow, Jennifer K.; Smitherman, Sonet; Kilts, Clinton D.

    2015-01-01

    Current neurocircuitry models of PTSD focus on the neural mechanisms that mediate hypervigilance for threat and fear inhibition/extinction learning. Less focus has been directed towards explaining social deficits and heightened risk of revictimization observed among individuals with PTSD related to physical or sexual assault. The purpose of the present study was to foster more comprehensive theoretical models of PTSD by testing the hypothesis that assault-related PTSD is associated with behavioral impairments in a social trust and reciprocity task and corresponding alterations in the neural encoding of social learning mechanisms. Adult women with assault-related PTSD (n=25) and control women (n=15) completed a multi-trial trust game outside of the MRI scanner. A subset of these participants (15 with PTSD and 14 controls) also completed a social and non-social reinforcement learning task during 3T fMRI. Brain regions that encoded the computationally modeled parameters of value expectation, prediction error, and volatility (i.e., uncertainty) were defined and compared between groups. The PTSD group demonstrated slower learning rates during the trust game and social prediction errors had a lesser impact on subsequent investment decisions. PTSD was also associated with greater encoding of negative expected social outcomes in perigenual anterior cingulate cortex and bilateral middle frontal gyri, and greater encoding of social prediction errors in the left temporoparietal junction. These data suggest mechanisms of PTSD-related deficits in social functioning and heightened risk for re-victimization in assault victims; however, comorbidity in the PTSD group and the lack of a trauma-exposed control group temper conclusions about PTSD specifically. PMID:25769397

  8. Novel biomarkers for early diagnosis of acute kidney injury after cardiac surgery in adults

    PubMed Central

    Kališnik, Jurij Matija

    2016-01-01

    Acute kidney injury after cardiac surgery with cardiopulmonary bypass is a common and serious complication and it is associated with increased morbidity and mortality. Diagnosis of acute kidney injury is based on the serum creatinine levels which rise several hours to days after the initial injury. Thus, novel biomarkers that will enable faster diagnosis are needed in clinical practice. There are numerous urine and serum proteins that indicate kidney injury and are under extensive research. Despite promising basic research results and assembled data, which indicate superiority of some biomarkers to creatinine, we are still awaiting clinical application. PMID:27212976

  9. Inhibition of SOCs Attenuates Acute Lung Injury Induced by Severe Acute Pancreatitis in Rats and PMVECs Injury Induced by Lipopolysaccharide.

    PubMed

    Wang, Guanyu; Zhang, Jingwen; Xu, Caiming; Han, Xiao; Gao, Yanyan; Chen, Hailong

    2016-06-01

    Acute lung injury (ALI) is a critical complication of the severe acute pancreatitis (SAP), characterized by increased pulmonary permeability with high mortality. Pulmonary microvascular endothelial cells (PMVECs) injury and apoptosis play a key role in ALI. Previous studies indicated that store-operated calcium entry (SOCE) could regulate a variety of cellular processes. The present study was to investigate the effects of SOCE inhibition on ALI induced by SAP in Sprague-Dawley rats, and PMVECs injury induced by lipopolysaccharide (LPS). Rat model of SAP-associated ALI were established by the retrograde infusion of sodium deoxycholate. Serum levels of amylase, TNF-α, and IL-6, histological changes, water content of the lung, oxygenation index, and ultrastructural changes of PMVECs were examined in ALI rats with or without store-operated Ca(2+) channels (SOCs) pharmacological inhibitor (2-aminoethoxydiphenyl borate, 2-APB) pretreatment. For in vitro studies, PMVECs were transiently transfected with or without small interfering RNA (siRNA) against calcium release-activated calcium channel protein1 (Orai1) and stromal interaction molecule1 (STIM1), the two main molecular constituents of SOCs, then exposed to LPS. The viability of PMVECs was determined. The expression of STIM1, Orai1, Bax, and caspase3, both in lung tissue and in PMVECs, were assessed by quantitative real-time PCR and western blot. Administration of sodium deoxycholate upregulated the expression of SOCs proteins in lung tissue. Similarly, the SOCs proteins were increased in PMVECs induced by LPS. 2-APB reduced the serum levels of amylase, TNF-α, and IL-6, and attenuated lung water content and histological findings. In addition, the decreased oxygenation index and ultrastructural damage in PMVECs associated with SAP were ameliorated after administration of 2-APB. Knockdown of STIM1 and Orai1 inhibited LPS-induced PMVECs death. Furthermore, blockade of SOCE significantly suppressed Orai1, STIM1, Bax

  10. Time representation of mitochondrial morphology and function after acute spinal cord injury

    PubMed Central

    Jia, Zhi-qiang; Li, Gang; Zhang, Zhen-yu; Li, Hao-tian; Wang, Ji-quan; Fan, Zhong-kai; Lv, Gang

    2016-01-01

    Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na+-K+-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged. PMID:26981103

  11. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury.

    PubMed

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L J; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A; McDevitt, Michael R

    2016-03-23

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)-mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, includingTrp53,Mep1b,Ctr1, andEGFP A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1band fCNT/siTrp53significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  12. NOS-2 Inhibition in Phosgene-Induced Acute Lung Injury

    PubMed Central

    Filipczak, Piotr T.; Senft, Albert P.; Seagrave, JeanClare; Weber, Waylon; Kuehl, Philip J.; Fredenburgh, Laura E.; McDonald, Jacob D.; Baron, Rebecca M.

    2015-01-01

    Phosgene exposure via an industrial or warfare release produces severe acute lung injury (ALI) with high mortality, characterized by massive pulmonary edema, disruption of epithelial tight junctions, surfactant dysfunction, and oxidative stress. There are no targeted treatments for phosgene-induced ALI. Previous studies demonstrated that nitric oxide synthase 2 (NOS-2) is upregulated in the lungs after phosgene exposure; however, the role of NOS-2 in the pathogenesis of phosgene-induced ALI remains unknown. We previously demonstrated that NOS-2 expression in lung epithelium exacerbates inhaled endotoxin-induced ALI in mice, mediated partially through downregulation of surfactant protein B (SP-B) expression. Therefore, we hypothesized that a selective NOS-2 inhibitor delivered to the lung epithelium by inhalation would mitigate phosgene-induced ALI. Inhaled phosgene produced increases in bronchoalveolar lavage fluid protein, histologic lung injury, and lung NOS-2 expression at 24 h. Administration of the selective NOS-2 inhibitor 1400 W via inhalation, but not via systemic delivery, significantly attenuated phosgene-induced ALI and preserved epithelial barrier integrity. Furthermore, aerosolized 1400 W augmented expression of SP-B and prevented downregulation of tight junction protein zonula occludens 1 (ZO-1), both critical for maintenance of normal lung physiology and barrier integrity. We also demonstrate for the first time that NOS-2-derived nitric oxide downregulates the ZO-1 expression at the transcriptional level in human lung epithelial cells, providing a novel target for ameliorating vascular leak in ALI. Our data demonstrate that lung NOS-2 plays a critical role in the development of phosgene-induced ALI and suggest that aerosolized NOS-2 inhibitors offer a novel therapeutic strategy for its treatment. PMID:25870319

  13. Hyperglycemia and acute kidney injury in critically ill children

    PubMed Central

    Gordillo, Roberto; Ahluwalia, Tania; Woroniecki, Robert

    2016-01-01

    Background Hyperglycemia and acute kidney injury (AKI) are common in critically ill children and have been associated with higher morbidity and mortality. The incidence of AKI in children is difficult to estimate because of the lack of a standard definition for AKI. The pediatric RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria can be used to define AKI in children. Various biomarkers in urine and blood have been studied to detect AKI in critically ill children. However, it is not clear whether hyperglycemia is associated with AKI. Our objective was to evaluate the effect of hyperglycemia on kidney function and its effect on neutrophil gelatinase-associated lipocalin (NGAL) in children. Methods We studied retrospective and prospective cohorts of pediatric critically ill subjects admitted to the pediatric intensive care unit (PICU). We analyzed data from admission that included estimated glomerular filtration rate, plasma and urine NGAL, serum glucose and peak glycemia (highest glycemia during PICU admission), and length of hospital and PICU stay from two different institutions. Results We found that the prevalence of hyperglycemia was 89% in the retrospective cohort and 86% in the prospective cohort, P=0.99. AKI was associated with peak glycemia, P=0.03. There was a statistically significant correlation between peak glycemia and hospital and PICU stays, P=<0.001 and P<0.001, respectively. Urine NGAL and plasma NGAL were not statistically different in subjects with and without hyperglycemia, P=0.99 and P=0.85, respectively. Subjects on vasopressors had lower estimated glomerular filtration rate and higher glycemia, P=0.01 and P=0.04, respectively. Conclusion We conclude that in critically ill children, hyperglycemia is associated with AKI and longer PICU stays. PMID:27601931

  14. Early Identification of Patients at Risk of Acute Lung Injury

    PubMed Central

    Gajic, Ognjen; Dabbagh, Ousama; Park, Pauline K.; Adesanya, Adebola; Chang, Steven Y.; Hou, Peter; Anderson, Harry; Hoth, J. Jason; Mikkelsen, Mark E.; Gentile, Nina T.; Gong, Michelle N.; Talmor, Daniel; Bajwa, Ednan; Watkins, Timothy R.; Festic, Emir; Yilmaz, Murat; Iscimen, Remzi; Kaufman, David A.; Esper, Annette M.; Sadikot, Ruxana; Douglas, Ivor; Sevransky, Jonathan

    2011-01-01

    Rationale: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. Objectives: To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). Methods: In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. Measurements and Main Results: Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1–4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78–0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9–5.7). Conclusions: ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772). PMID:20802164

  15. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury

    PubMed Central

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J.; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)–mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, including Trp53, Mep1b, Ctr1, and EGFP. A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1b and fCNT/siTrp53 significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  16. Measuring dead-space in acute lung injury.

    PubMed

    Kallet, R H

    2012-11-01

    Several recent studies have advanced our understanding of dead-space ventilation in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). They have demonstrated the utility of measuring physiologic dead-space-to-tidal volume ratio (VD/VT) and related variables in assessing outcomes as well as therapeutic interventions. These studies have included the evaluation of mortality risk, pulmonary perfusion, as well as the effectiveness of drug therapy, prone positioning, positive end-expiratory pressure (PEEP) titration, and inspiratory pattern in improving gas exchange. In patients with ALI/ARDS managed with lung-protective ventilation a significant relationship between elevated VD/VT and increased mortality continues to be reported in both early and intermediate phases of ALI/ARDS. Some clinical evidence now supports the suggestion that elevated VD/VT in part reflects the severity of pulmonary vascular endothelial damage. Monitoring VD/VT also appears useful in assessing alveolar recruitment when titrating PEEP and may be a particularly expedient method for assessing the effectiveness of prone positioning. It also has revealed how subtle manipulations of inspiratory time and pattern can improve CO(2) excretion. Much of this has been accomplished using volumetric capnography. This allows for more sophisticated measurements of pulmonary gas exchange function including: alveolar VD/VT, the volume of CO(2) excretion and the slope of the alveolar plateau which reflects ventilation: perfusion heterogeneity. Many of these measurements now can be made non-invasively which should only increase the research and clinical utility of volumetric capnography in studying and managing patients with ALI/ARDS. PMID:22858884

  17. [Disglycemia in patients with acute kidney injury in the ICU].

    PubMed

    Fiaccadori, E; Sabatino, A; Morabito, S; Bozzoli, L; Donadio, C; Maggiore, U; Regolisti, G

    2015-01-01

    Derangements of glucose metabolism are common among critically ill patients. Critical illness- associated hyperglycemia (CIAH) is characterized by raised blood glucose levels in association with an acute event that is reversible after resolution of the underlying disease. CIAH has many causes, such as changes in counter-regulatory hormone status, release of sepsis mediators, insulin resistance, drugs and nutritional factors. It is associated with increased mortality risk. This association appears to be strongly influenced by diabetes mellitus as a comorbidity, suggesting the need for an accurate individualization of glycemic targets according to baseline glycemic status. Hypoglycemia is also very common in this clinical context and it has a negative prognostic impact. Many studies based on intensive insulin treatment protocols targeting normal blood glucose values have in fact documented both an increased incidence of hypoglycemia and an increased mortality risk. Finally, glycemic control in the ICU is made even more complex in the presence of acute kidney injury. On one hand, there is in fact a reduction of both the renal clearance of insulin and of gluconeogenesis by the kidney. On the other hand, the frequent need for renal replacement therapy (dialysis / hemofiltration) may result in an energy intake excess, under the form of citrate, lactate and glucose in the dialysate/reinfusion fluids. With regard to the possible renal protective effects afforded by intensive glycemic control protocols, the presently available evidence does not support a reduction in the incidence of AKI and/or the need for RRT with this approach, when compared with standard glucose control. Thus, the most recent guidelines now suggest higher blood glucose targets (<180 mg/dl or 140-180 mg/dl) than in the past (80-110 mg/dl). Albeit with limited evidence, it seems reasonable to extend these indications also to patients with AKI in the intensive care unit. Further studies are needed in order

  18. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models.

    PubMed

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models. PMID:26199634

  19. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    PubMed Central

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models. PMID:26199634

  20. The radiology of pulmonary complications associated with acute spinal cord injury.

    PubMed

    Scher, A T

    1982-08-28

    Pulmonary complications after acute cervical spinal cord injury are common. Paralysis of the intercostal muscles leads to decreased respiratory function. In addition, injuries of the thoracic cage, pleura and lungs are commonly associated with spinal injuries. A survey of radiologically demonstrable pulmonary complications in 50 patients with acute tetraplegia has been made. Changes were present in 28% of the patients surveyed. The changes in pulmonary and haemodynamic function consequent upon cervical spinal cord injury are briefly described. Radiological manifestations of pulmonary complications due to decreased pulmonary function, direct pulmonary trauma and rare pulmonary complications of skeletal injury are reviewed. The value of routine and intensive radiographic monitoring of the chest in the patient with acute tetraplegia is emphasized, as clinical diagnosis is hampered in the absence of motor and sensory function. PMID:7112294

  1. Dyschloremia Is a Risk Factor for the Development of Acute Kidney Injury in Critically Ill Patients

    PubMed Central

    Shao, Min; Li, Guangxi; Sarvottam, Kumar; Wang, Shengyu; Thongprayoon, Charat; Dong, Yue; Gajic, Ognjen

    2016-01-01

    Introduction Dyschloremia is common in critically ill patients, although its impact has not been well studied. We investigated the epidemiology of dyschloremia and its associations with the incidence of acute kidney injury and other intensive care unit outcomes. Material and Methods This is a single-center, retrospective cohort study at Mayo Clinic Hospital—Rochester. All adult patients admitted to intensive care units from January 1st, 2006, through December 30th, 2012 were included. Patients with known acute kidney injury and chronic kidney disease stage 5 before intensive care unit admission were excluded. We evaluated the association of dyschloremia with ICU outcomes, after adjustments for the effect of age, gender, Charlson comorbidity index and severity of illness score. Results A total of 6,025 patients were enrolled in the final analysis following the implementation of eligibility criteria. From the cohort, 1,970 patients (33%) developed acute kidney injury. Of the total patients enrolled, 4,174 had a baseline serum chloride. In this group, 1,530 (37%) had hypochloremia, and 257 (6%) were hyperchloremic. The incidence of acute kidney injury was higher in hypochloremic and hyperchloremic patients compared to those with a normal serum chloride level (43% vs.30% and 34% vs. 30%, respectively; P < .001). Baseline serum chloride was lower in the acute kidney injury group vs. the non-acute kidney injury group [100 mmol/L (96–104) vs. 102 mmol/L (98–105), P < .0001]. In a multivariable logistic regression model, baseline serum chloride of ≤94 mmol/L found to be independently associated with the risk of acute kidney injury (OR 1.7, 95% CI 1.1–2.6; P = .01). Discussion Dyschloremia is common in critically ill patients, and severe hypochloremia is independently associated with an increased risk of development of acute kidney injury. PMID:27490461

  2. Plasma FGF23 levels increase rapidly after acute kidney injury

    PubMed Central

    Christov, Marta; Waikar, Sushrut; Pereira, Renata; Havasi, Andrea; Leaf, David E.; Goltzman, David; Pajevic, Paola Divieti; Wolf, Myles; Jüppner, Harald

    2013-01-01

    Emerging evidence suggests that fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). In order to determine how early this increase occurs we used a murine folic acid nephropathy model and found that plasma FGF23 levels increased significantly from baseline already after 1 hour of AKI, with an 18-fold increase at 24 hours. Similar elevations of FGF23 levels were found when AKI was induced in mice with osteocyte-specific parathyroid hormone receptor ablation or the global deletion of parathyroid hormone or vitamin D receptor, indicating that the increase in FGF23 was independent of parathyroid hormone and vitamin D signaling. Furthermore, FGF23 levels increased to a similar extent in wild-type mice maintained on normal or phosphate-depleted diets prior to induction of AKI, indicating that the marked FGF23 elevation is at least partially independent of dietary phosphate. Bone production of FGF23 was significantly increased in AKI. The half-life of intravenously administered recombinant FGF23 was only modestly increased. Consistent with the mouse data, plasma FGF23 levels rose 15.9-fold by 24 hours following cardiac surgery in patients who developed AKI. The levels were significantly higher than in those without postoperative AKI. Thus, circulating FGF23 levels rise rapidly during AKI in rodents and humans. In mice this increase is independent of established modulators of FGF23 secretion. PMID:23657144

  3. Epithelial cell apoptosis causes acute lung injury masquerading as emphysema.

    PubMed

    Mouded, Majd; Egea, Eduardo E; Brown, Matthew J; Hanlon, Shane M; Houghton, A McGarry; Tsai, Larry W; Ingenito, Edward P; Shapiro, Steven D

    2009-10-01

    Theories of emphysema traditionally revolved around proteolytic destruction of extracellular matrix. Models have recently been developed that show airspace enlargement with the induction of pulmonary cell apoptosis. The purpose of this study was to determine the mechanism by which a model of epithelial cell apoptosis caused airspace enlargement. Mice were treated with either intratracheal microcystin (MC) to induce apoptosis, intratracheal porcine pancreatic elastase (PPE), or their respective vehicles. Mice from all groups were inflated and morphometry was measured at various time points. Physiology measurements were performed for airway resistance, tissue elastance, and lung volumes. The groups were further analyzed by air-saline quasistatic measurements, surfactant staining, and surfactant functional studies. Mice treated with MC showed evidence of reversible airspace enlargement. In contrast, PPE-treated mice showed irreversible airspace enlargement. The airspace enlargement in MC-treated mice was associated with an increase in elastic recoil due to an increase in alveolar surface tension. PPE-treated mice showed a loss of lung elastic recoil and normal alveolar surface tension, a pattern more consistent with human emphysema. Airspace enlargement that occurs with the MC model of pulmonary epithelial cell apoptosis displays physiology distinct from human emphysema. Reversibility, restrictive physiology due to changes in surface tension, and alveolar enlargement associated with heterogeneous alveolar collapse are most consistent with a mild acute lung injury. Inflation near total lung capacity gives the appearance of enlarged alveoli as neighboring collapsed alveoli exert tethering forces. PMID:19188661

  4. Science review: Searching for gene candidates in acute lung injury

    PubMed Central

    Grigoryev, Dmitry N; Finigan, James H; Hassoun, Paul; Garcia, Joe GN

    2004-01-01

    Acute lung injury (ALI) is a complex and devastating illness, often occurring within the setting of sepsis, and carries an annual mortality rate of 30–50%. Although the genetic basis of ALI has not been fully established, an increasing body of evidence suggests that genetic predisposition contributes to disease susceptibility and severity. Significant difficulty exists, however, in defining the exact nature of these genetic factors, including large phenotypic variance, incomplete penetrance, complex gene–environment interactions, and strong potential for locus heterogeneity. We utilized the candidate gene approach and an ortholog gene database to provide relevant gene ontologies and insights into the genetic basis of ALI. We employed a Medline search of selected basic and clinical studies in the English literature and studies sponsored by the HopGene National Institutes of Health sponsored Program in Genomic Applications. Extensive gene expression profiling studies in animal models of ALI (rat, murine, canine), as well as in humans, were performed to identify potential candidate genes . We identified a number of candidate genes for ALI, with blood coagulation and inflammation gene ontologies being the most highly represented. The candidate gene approach coupled with extensive gene profiling and novel bioinformatics approaches is a valuable way to identify genes that are involved in ALI. PMID:15566614

  5. Contrast-Induced Acute Kidney Injury: Definition, Epidemiology, and Outcome

    PubMed Central

    Meinel, Felix G.; De Cecco, Carlo N.; Schoepf, U. Joseph

    2014-01-01

    Contrast-induced acute kidney injury (CI-AKI) is commonly defined as a decline in kidney function occurring in a narrow time window after administration of iodinated contrast material. The incidence of AKI after contrast material administration greatly depends on the specific definition and cutoff values used. Although self-limiting in most cases, postcontrast AKI carries a risk of more permanent renal insufficiency, dialysis, and death. The risk of AKI from contrast material, in particular when administered intravenously for contrast-enhanced CT, has been exaggerated by older, noncontrolled studies due to background fluctuations in renal function. More recent evidence from controlled studies suggests that the risk is likely nonexistent in patients with normal renal function, but there may be a risk in patients with renal insufficiency. However, even in this patient population, the risk of CI-AKI is probably much smaller than traditionally assumed. Since volume expansion is the only preventive strategy with a convincing evidence base, liberal hydration should be encouraged to further minimize the risk. The benefits of the diagnostic information gained from contrast-enhanced examinations will still need to be balanced with the potential risk of CI-AKI for the individual patient and clinical scenario. PMID:24734250

  6. Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status

    PubMed Central

    Zhou, Hai Ying; Chen, Tian Wu; Zhang, Xiao Ming

    2016-01-01

    Acute kidney injury (AKI) is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progression of AKI. The early assessment of these changes remains a challenge. Many established approaches are not applicable to humans because of their invasiveness. Functional renal magnetic resonance (MR) imaging offers an alternative assessment tool that could be used to evaluate renal morphology and function noninvasively and simultaneously. Thus, the purpose of this review is to illustrate the principle, application, and role of the techniques of functional renal MR imaging, including blood oxygen level-dependent imaging, arterial spin labeling, and diffusion-weighted MR imaging, in the management of AKI. The use of gadolinium in MR imaging may exacerbate renal impairment and cause nephrogenic systemic fibrosis. Therefore, dynamic contrast-enhanced MR imaging will not be discussed in this paper. PMID:26925411

  7. Arctigenin attenuates lipopolysaccharide-induced acute lung injury in rats.

    PubMed

    Shi, Xianbao; Sun, Hongzhi; Zhou, Dun; Xi, Huanjiu; Shan, Lina

    2015-04-01

    Arctigenin (ATG) has been reported to possess anti-inflammatory properties. However, the effects of ATG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. In the present study, our investigation was designed to reveal the effect of ATG on LPS-induced ALI in rats. We found that ATG pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the decreased levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-1 (IL-6) in the bronchoalveolar lavage fluid. Furthermore, ATG downregulated the expression of nuclear factor kappa B (NF-κB) p65, promoted the phosphorylation of inhibitor of nuclear factor-κB-α (IκBα) and activated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPKα) in the lung tissues. Our results suggested that ATG attenuates the LPS-induced ALI via activation of AMPK and suppression of NF-κB signaling pathway. PMID:25008149

  8. Bath salt intoxication causing acute kidney injury requiring hemodialysis.

    PubMed

    Regunath, Hariharan; Ariyamuthu, Venkatesh Kumar; Dalal, Pranavkumar; Misra, Madhukar

    2012-10-01

    Traditional bath salts contain a combination of inorganic salts like Epsom salts, table salt, baking soda, sodium metaphosphate, and borax that have cleansing properties. Since 2010, there have been rising concerns about a new type of substance abuse in the name of "bath salts." They are beta-ketone amphetamine analogs and are derivates of cathinone, a naturally occurring amphetamine analog found in the "khat" plant (Catha edulis). Effects reported with intake included increased energy, empathy, openness, and increased libido. Serious adverse effects reported with intoxication included cardiac, psychiatric, and neurological signs and symptoms. Not much is known about the toxicology and metabolism of these compounds. They inhibit monoamine reuptake (dopamine, nor epinephrine, etc.) and act as central nervous system stimulants with high additive and abuse potential because of their clinical and biochemical similarities to effects from use of cocaine, amphetamine, and 3,4-methylenedioxy-N-methylamphetamine. Deaths associated with use of these compounds have also been reported. We report a case of acute kidney injury associated with the use of "bath salt" pills that improved with hemodialysis. PMID:23036036

  9. Wogonoside ameliorates lipopolysaccharide-induced acute lung injury in mice.

    PubMed

    Zhang, Liang; Ren, Yi; Yang, Chengliang; Guo, Yue; Zhang, Xiaojing; Hou, Gang; Guo, Xinjin; Sun, Nan; Liu, Yongyu

    2014-12-01

    Wogonoside has been reported to have anti-inflammatory properties. In this study, we evaluated the effect of wogonoside on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice with ALI, induced by intranasal instillation of LPS, were treated with wogonoside 1 h prior to LPS exposure. Mice treated with LPS alone showed significantly increased TNF-α, IL-6, and IL-1β levels in the bronchoalveolar lavage fluid (BALF). When pretreated with wogonoside, the TNF-α, IL-6, and IL-1β levels were significantly decreased. Meanwhile, wogonoside significantly inhibited LPS-induced increases in the macrophage and neutrophil infiltration of lung tissues and markedly attenuated myeloperoxidase activity. Furthermore, wogonoside inhibited the TLR4 expression and the phosphorylation of NF-κB p65, and IκB induced by LPS. In conclusion, our results indicate that wogonoside exhibits a protective effect on LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways. PMID:24854163

  10. Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery

    PubMed Central

    Shin, Su Rin; Kim, Won Ho; Kim, Dong Joon; Shin, Il-Woo; Sohn, Ju-Tae

    2016-01-01

    The incidence of acute kidney injury after cardiac surgery (CS-AKI) ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI. PMID:27419130

  11. Clinical Predictors of Acute Kidney Injury Following Snake Bite Envenomation

    PubMed Central

    Dharod, Mrudul V; Patil, Tushar B; Deshpande, Archana S; Gulhane, Ragini V; Patil, Mangesh B; Bansod, Yogendra V

    2013-01-01

    Background: Snake bite envenomation is a major public health concern in developing countries. Acute kidney injury (AKI) is as important cause of mortality in patients with vasculotoxic snake bite. Aims: This study was to evaluate the clinical profile of snake bite patients and to determine the predictors of developing AKI following snake bite. Materials and Methods: Two hundred and eighty-one patients with snake envenomation were included. Eighty-seven patients developed AKI (Group A) and 194 (Group B) did not. History, examination findings and investigations results were recorded and compared between the two groups. Results: In group A, 61 (70.11%) patients were male and in group B, 117 (60.30%) patients were male. Out of 281 patients, 232 had cellulitis, 113 had bleeding tendencies, 87 had oliguria, 76 had neuroparalysis, and 23 had hypotension at presentation. After multivariate analysis, bite to hospital time (P = 0.016), hypotension (P = 0.000), albuminuria (P = 0.000), bleeding time (P = 0.000), prothrombin time (P = 0.000), hemoglobin (P = 0.000) and total bilirubin (P = 0.010) were significant independent predictors of AKI. Conclusions: AKI developed in 30.96% of patients with snake bite, leading to mortality in 39.08% patients. Factors associated with AKI are bite to hospital time, hypotension, albuminuria, prolonged bleeding time, prolonged prothrombin time, low hemoglobin and a high total bilirubin. PMID:24350071

  12. Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate.

    PubMed

    Bowers, Christian A; Kundu, Bornali; Hawryluk, Gregory W J

    2016-06-01

    Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care. PMID:27482201

  13. Advances in the rehabilitation management of acute spinal cord injury.

    PubMed

    Ditunno, John F; Cardenas, Diana D; Formal, Christopher; Dalal, Kevin

    2012-01-01

    Aggressive assessment and management of the secondary complications in the hours and days following spinal cord injury (SCI) leads to restoration of function in patients through intervention by a team of rehabilitation professionals. The recent certification of SCI physicians, newly validated assessments of impairment and function measures, and international databases agreed upon by SCI experts should lead to documentation of improved rehabilitation care. This chapter highlights recent advances in assessment and treatment based on evidence-based classification of literature reviews and expert opinion in the acute phase of SCI. A number of these reviews are the product of the Consortium for Spinal Cord Medicine, which offers clinical practice guidelines for healthcare professionals. Recognition of and early intervention for problems such as bradycardia, orthostatic hypotension, deep vein thrombosis/pulmonary embolism, and early ventilatory failure will be addressed although other chapters may discuss some issues in greater detail. Early assessment and intervention for neurogenic bladder and bowel function has proven effective in the prevention of renal failure and uncontrolled incontinence. Attention to overuse and disuse with training and advanced technology such as functional electrical stimulation have reduced pain and disability associated with upper extremity deterioration and improved physical fitness. Topics such as chronic pain, spasticity, sexual dysfunction, and pressure sores will be covered in more detail in additional chapters. However, the comprehensive and integrated rehabilitation by specialized SCI teams of physicians, nurses, therapists, social workers, and psychologists immediately following SCI has become the standard of care throughout the world. PMID:23098713

  14. Inhibition of Neutrophil Exocytosis Ameliorates Acute Lung Injury in Rats

    PubMed Central

    Uriarte, Silvia M.; Rane, Madhavi J.; Merchant, Michael L.; Jin, Shunying; Lentsch, Alex B.; Ward, Richard A.; McLeish, Kenneth R.

    2013-01-01

    Exocytosis of neutrophil granules contributes to acute lung injury (ALI) induced by infection or inflammation, suggesting that inhibition of neutrophil exocytosis in vivo could be a viable therapeutic strategy. This study was conducted to determine the effect of a cell-permeable fusion protein that inhibits neutrophil exocytosis (TAT-SNAP-23) on ALI using an immune complex deposition model in rats. The effect of inhibition of neutrophil exocytosis by intravenous administration of TAT-SNAP-23 on ALI was assessed by albumin leakage, neutrophil infiltration, lung histology, and proteomic analysis of bronchoalveolar lavage fluid (BALf). Administration of TAT-SNAP-23, but not TAT-Control, significantly reduced albumin leakage, total protein levels in the BALf, and intra-alveolar edema and hemorrhage. Evidence that TAT-SNAP-23 inhibits neutrophil exocytosis included a reduction in plasma membrane CD18 expression by BALf neutrophils and a decrease in neutrophil granule proteins in BALf. Similar degree of neutrophil accumulation in the lungs and/or BALf suggests that TAT-SNAP-23 did not alter vascular endothelial cell function. Proteomic analysis of BALf revealed that components of the complement and coagulation pathways were significantly reduced in BALf from TAT-SNAP-23-treated animals. Our results indicate that administration of a TAT-fusion protein that inhibits neutrophil exocytosis reduces in vivo ALI. Targeting neutrophil exocytosis is a potential therapeutic strategy to ameliorate ALI. PMID:23364427

  15. Early detection of acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Jefferies, John Lynn; Devarajan, Prasad

    2016-01-01

    Acute kidney injury (AKI) is increasingly recognized as a common problem in children undergoing cardiac surgery, with well documented increases in morbidity and mortality in both the short and the long term. Traditional approaches to the identification of AKI such as changes in serum creatinine have revealed a large incidence in this population with significant negative impact on clinical outcomes. However, the traditional diagnostic approaches to AKI diagnosis have inherent limitations that may lead to under-diagnosis of this pathologic process. There is a dearth of randomized controlled trials for the prevention and treatment of AKI associated with cardiac surgery, at least in part due to the paucity of early predictive biomarkers. Novel non-invasive biomarkers have ushered in a new era that allows for earlier detection of AKI. With these new diagnostic tools, a more consistent approach can be employed across centers that may facilitate a more accurate representation of the actual prevalence of AKI and more importantly, clinical investigation that may minimize the occurrence of AKI following pediatric cardiac surgery. A thoughtful management approach is necessary to mitigate the effects of AKI after cardiac surgery, which is best accomplished in close collaboration with pediatric nephrologists. Long-term surveillance for improvement in kidney function and potential development of chronic kidney disease should also be a part of the comprehensive management strategy. PMID:27429538

  16. Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status.

    PubMed

    Zhou, Hai Ying; Chen, Tian Wu; Zhang, Xiao Ming

    2016-01-01

    Acute kidney injury (AKI) is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progression of AKI. The early assessment of these changes remains a challenge. Many established approaches are not applicable to humans because of their invasiveness. Functional renal magnetic resonance (MR) imaging offers an alternative assessment tool that could be used to evaluate renal morphology and function noninvasively and simultaneously. Thus, the purpose of this review is to illustrate the principle, application, and role of the techniques of functional renal MR imaging, including blood oxygen level-dependent imaging, arterial spin labeling, and diffusion-weighted MR imaging, in the management of AKI. The use of gadolinium in MR imaging may exacerbate renal impairment and cause nephrogenic systemic fibrosis. Therefore, dynamic contrast-enhanced MR imaging will not be discussed in this paper. PMID:26925411

  17. Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate

    PubMed Central

    Bowers, Christian A.; Kundu, Bornali; Hawryluk, Gregory W. J.

    2016-01-01

    Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care. PMID:27482201

  18. Hospital Mortality in the United States following Acute Kidney Injury

    PubMed Central

    Rezaee, Michael E.; Marshall, Emily J.; Matheny, Michael E.

    2016-01-01

    Acute kidney injury (AKI) is a common reason for hospital admission and complication of many inpatient procedures. The temporal incidence of AKI and the association of AKI admissions with in-hospital mortality are a growing problem in the world today. In this review, we discuss the epidemiology of AKI and its association with in-hospital mortality in the United States. AKI has been growing at a rate of 14% per year since 2001. However, the in-hospital mortality associated with AKI has been on the decline starting with 21.9% in 2001 to 9.1 in 2011, even though the number of AKI-related in-hospital deaths increased almost twofold from 147,943 to 285,768 deaths. We discuss the importance of the 71% reduction in AKI-related mortality among hospitalized patients in the United States and draw on the discussion of whether or not this is a phenomenon of hospital billing (coding) or improvements to the management of AKI. PMID:27376083

  19. Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats.

    PubMed

    Lin, Hen I; Chu, Shi Jye; Hsu, Kang; Wang, David

    2004-01-01

    In this study, we determined the effect of inhaled nitric oxide (NO) on the acute lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung. Typical acute lung injury was induced successfully by PMA during 60 min of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability, (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and protein concentration of the bronchoalveolar lavage fluid. Pretreatment with inhaled NO (30 ppm) significantly exacerbated acute lung injury. All of the parameters reflective of lung injury increased significantly except PAP (P<0.05). Coadministration of Nomega-nitro-L-arginine methyl ester (L-NAME) (5 mM) attenuated the detrimental effect of inhaled NO in PMA-induced lung injury, except for PAP. In addition, L-NAME (5 mM) significantly attenuated PMA-induced acute lung injury except for PAP. These experimental data suggest that inhaled NO significantly exacerbated acute lung injury induced by PMA in rats. L-NAME attenuated the detrimental effect of inhaled NO. PMID:14643171

  20. Incidence and severity of reported acute sports injuries in 35 sports using insurance registry data.

    PubMed

    Åman, M; Forssblad, M; Henriksson-Larsén, K

    2016-04-01

    Acute injuries in sport are still a problem where limited knowledge of incidence and severity in different sports at national level exists. In Sweden, 80% of the sports federations have their mandatory injury insurance for all athletes in the same insurance company and injury data are systematically kept in a national database. The aim of the study was to identify high-risk sports with respect to incidence of acute and severe injuries in 35 sports reported to the database. The number and incidences of injuries as well as injuries leading to permanent medical impairment (PMI) were calculated during 2008-2011. Each year approximately 12,000 injuries and 1,162,660 licensed athletes were eligible for analysis. Eighty-five percent of the injuries were reported in football, ice hockey, floorball, and handball. The highest injury incidence as well as PMI was in motorcycle, handball, skating, and ice hockey. Females had higher risk of a PMI compared with males in automobile sport, handball, floorball, and football. High-risk sports with numerous injuries and high incidence of PMI injuries were motorcycle, handball, ice hockey, football, floorball, and automobile sports. Thus, these sports ought to be the target of preventive actions at national level. PMID:25850826

  1. Critical care in the ED: potentially fatal asthma and acute lung injury syndrome

    PubMed Central

    Hodder, Rick

    2012-01-01

    Emergency department clinicians are frequently called upon to assess, diagnose, and stabilize patients who present with acute respiratory failure. This review describes a rapid initial approach to acute respiratory failure in adults, illustrated by two common examples: (1) an airway disease – acute potentially fatal asthma, and (2) a pulmonary parenchymal disease – acute lung injury/acute respiratory distress syndrome. As such patients are usually admitted to hospital, discussion will be focused on those initial management aspects most relevant to the emergency department clinician. PMID:27147862

  2. Platelet-rich plasma (PRP) treatment of sports-related severe acute hamstring injuries

    PubMed Central

    Guillodo, Yannick; Madouas, Gwénaelle; Simon, Thomas; Le Dauphin, Hermine; Saraux, Alain

    2015-01-01

    Summary Purpose hamstring injury is the most common musculoskeletal disorder and one of the main causes of missed sporting events. Shortening the time to return to play (TTRTP) is a priority for athletes and sports medicine practitioners. Hypothesis platelet-rich plasma (PRP) injection at the site of severe acute hamstring injury increases the healing rate and shortens the TTRTP. Study design Cohort study. Methods all patients with ultrasonography and MRI evidence of severe acute hamstring injury between January 2012 and March 2014 were offered PRP treatment. Those who accepted received a single intramuscular PRP injection within 8 days post-injury; the other patients served as controls. The same standardized rehabilitation program was used in both groups. A physical examination and ultrasonography were performed 10 and 30 days post-injury, then a phone interview 120 days post-injury, to determine the TTRTP at the pre-injury level. Results of 34 patients, 15 received PRP and 19 did not. Mean TTRTP at the pre-injury level was 50.9±10.7 days in the PRP group and 52.8±15.7 days in the control group. The difference was not statistically significant. Conclusion a single intramuscular PRP injection did not shorten the TTRTP in sports people with severe acute hamstring injuries. PMID:26958537

  3. Minimal Effects of Acute Liver Injury/Acute Liver Failure on Hemostasis as Assessed by Thromboelastography

    PubMed Central

    Stravitz, R. Todd; Lisman, Ton; Luketic, Velimir A.; Sterling, Richard K.; Puri, Puneet; Fuchs, Michael; Ibrahim, Ashraf; Lee, William M.; Sanyal, Arun J.

    2016-01-01

    Background & Aims Patients with acute liver injury/failure (ALI/ALF) are assumed to have a bleeding diathesis on the basis of elevated INR; however, clinically significant bleeding is rare. We hypothesized that patients with ALI/ALF have normal hemostasis despite elevated INR Methods Fifty-one patients with ALI/ALF were studied prospectively using thromboelastography (TEG), which measures the dynamics and physical properties of clot formation in whole blood. ALI was defined as an INR ≥1.5 in a patient with no previous liver disease, and ALF as ALI with hepatic encephalopathy. Results Thirty-seven of 51 patients (73%) had ALF and 22 patients (43%) underwent liver transplantation or died. Despite a mean INR of 3.4±1.7 (range 1.5–9.6), mean TEG parameters were normal, and 5 individual TEG parameters were normal in 32 (63%). Low maximum amplitude, the measure of ultimate clot strength, was confined to patients with platelet counts <126 × 109/L. Maximum amplitude was higher in patients with ALF than ALI and correlated directly with venous ammonia concentrations and with increasing severity of liver injury assessed by elements of the systemic inflammatory response syndrome. All patients had markedly decreased procoagulant factor V and VII levels, which were proportional to decreases in anticoagulant proteins and inversely proportional to elevated factor VIII levels. Conclusions Despite elevated INR, most patients with ALI/ALF maintain normal hemostasis by TEG, the mechanisms of which include an increase in clot strength with increasing severity of liver injury, increased factor VIII levels, and a commensurate decline in pro- and anticoagulant proteins. PMID:21703173

  4. MicroRNA Regulation of Acute Lung Injury and Acute Respiratory Distress Syndrome.

    PubMed

    Rajasekaran, Subbiah; Pattarayan, Dhamotharan; Rajaguru, P; Sudhakar Gandhi, P S; Thimmulappa, Rajesh K

    2016-10-01

    The acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), is a very common condition associated with critically ill patients, which causes substantial morbidity and mortality worldwide. Despite decades of research, effective therapeutic strategies for clinical ALI/ARDS are not available. In recent years, microRNAs (miRNAs), small non-coding molecules have emerged as a major area of biomedical research as they post-transcriptionally regulate gene expression in diverse biological and pathological processes, including ALI/ARDS. In this context, this present review summarizes a large body of evidence implicating miRNAs and their target molecules in ALI/ARDS originating largely from studies using animal and cell culture model systems of ALI/ARDS. We have also focused on the involvement of miRNAs in macrophage polarization, which play a critical role in regulating the pathogenesis of ALI/ARDS. Finally, the possible future directions that might lead to novel therapeutic strategies for the treatment of ALI/ARDS are also reviewed. J. Cell. Physiol. 231: 2097-2106, 2016. © 2016 Wiley Periodicals, Inc. PMID:26790856

  5. Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation.

    PubMed

    Rodgers, Bradley K; Kumar, Avinash B

    2016-01-01

    Toxic epidermal necrolysis syndrome (TEN) is a rare severe cutaneous adverse drug reaction that involves skin and mucous membranes. We describe a case of TEN presenting with stage III acute kidney injury, rhabdomyolysis, and acute respiratory failure likely triggered by allopurinol for recently diagnosed gout. Prompt diagnosis, multidisciplinary management, including aggressive resuscitation, cardiorespiratory support, intravenous immunoglobulin therapy, and daily wound care resulted in a positive outcome despite a predicted mortality greater than 60%. Although allopurinol is a known triggering agent, TEN presenting with rhabdomyolysis and acute kidney injury is rare. PMID:24832386

  6. Prediction of acute renal failure following soft-tissue injury using the venous bicarbonate concentration.

    PubMed

    Muckart, D J; Moodley, M; Naidu, A G; Reddy, A D; Meineke, K R

    1992-12-01

    Sixty-four patients with soft-tissue injuries were studied prospectively to determine whether an initial venous bicarbonate concentration (VBC) of less than 17 mmol/L would predict the development of myoglobin-induced acute renal failure. The VBC was > 17 mmol/L in 59 patients, seven of whom had myoglobinuria. All recovered without renal complications. The remaining five patients all had VBC < 17 mmol/L and four had myoglobinuria. Acute renal failure developed in four patients (p < 0.001). The VBC on hospital arrival was the most accurate predictor of these patients' risk for the development of acute renal failure following soft-tissue injury. PMID:1474620

  7. THE 5-LIPOXYGENASE PATHWAY IS REQUIRED FOR ACUTE LUNG INJURY FOLLOWING HEMORRHAGIC SHOCK

    PubMed Central

    Eun, John C.; Moore, Ernest E.; Mauchley, David C.; Johnson, Chris A.; Meng, Xianzhong; Banerjee, Anirban; Wohlauer, Max V.; Zarini, Simona; Gijón, Miguel A.; Murphy, Robert C.

    2012-01-01

    The cellular and biochemical mechanisms leading to acute lung injury and subsequent multiple organ failure are only partially understood. In order to study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of acute lung injury, we used a murine experimental model of acute lung injury induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration as shown by immunofluorescence, and protein leakage into the alveolar space, were measured as markers of injury. We used liquid chromatography coupled to tandem mass spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar lavage fluid of experimental animals. MK886, a specific inhibitor of the 5-lipoxygenase pathway, as well as transgenic mice deficient in 5-lipoxygenase, were used to determine the role of this enzymatic pathway in this model. Leukotriene B4 and leukotriene C4 were consistently elevated in shock-treated mice compared to sham-treated mice. MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-lipoxygenase, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of acute lung injury induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury. PMID:22392149

  8. Altered Cerebellar White Matter Integrity in Patients with Mild Traumatic Brain Injury in the Acute Stage

    PubMed Central

    Wang, Zhongqiu; Wu, Wenzhong; Liu, Yongkang; Wang, Tianyao; Chen, Xiao; Zhang, Jianhua; Zhou, Guoxing; Chen, Rong

    2016-01-01

    Background and Purpose Imaging studies of traumatic brain injury demonstrate that the cerebellum is often affected. We aim to examine fractional anisotropy alteration in acute-phase mild traumatic brain injury patients in cerebellum-related white matter tracts. Materials and Methods This prospective study included 47 mild traumatic brain injury patients in the acute stage and 37 controls. MR imaging and neurocognitive tests were performed in patients within 7 days of injury. White matter integrity was examined by using diffusion tensor imaging. We used three approaches, tract-based spatial statistics, graphical-model-based multivariate analysis, and region-of-interest analysis, to detect altered cerebellar white matter integrity in mild traumatic brain injury patients. Results Results from three analysis methods were in accordance with each other, and suggested fractional anisotropy in the middle cerebellar peduncle and the pontine crossing tract was changed in the acute-phase mild traumatic brain injury patients, relative to controls (adjusted p-value < 0.05). Higher fractional anisotropy in the middle cerebellar peduncle was associated with worse performance in the fluid cognition composite (r = -0.289, p-value = 0.037). Conclusion Altered cerebellar fractional anisotropy in acute-phase mild traumatic brain injury patients is localized in specific regions and statistically associated with cognitive deficits detectable on neurocognitive testing. PMID:26967320

  9. Acute Kidney Injury Increases Risk of ESRD among Elderly

    PubMed Central

    Ishani, Areef; Xue, Jay L.; Himmelfarb, Jonathan; Eggers, Paul W.; Kimmel, Paul L.; Molitoris, Bruce A.; Collins, Allan J.

    2009-01-01

    Risk for ESRD among elderly patients with acute kidney injury (AKI) has not been studied in a large, representative sample. This study aimed to determine incidence rates and hazard ratios for developing ESRD in elderly individuals, with and without chronic kidney disease (CKD), who had AKI. In the 2000 5% random sample of Medicare beneficiaries, clinical conditions were identified using Medicare claims; ESRD treatment information was obtained from ESRD registration during 2 yr of follow-up. Our cohort of 233,803 patients were hospitalized in 2000, were aged ≥67 yr on discharge, did not have previous ESRD or AKI, and were Medicare-entitled for ≥2 yr before discharge. In this cohort, 3.1% survived to discharge with a diagnosis of AKI, and 5.3 per 1000 developed ESRD. Among patients who received treatment for ESRD, 25.2% had a previous history of AKI. After adjustment for age, gender, race, diabetes, and hypertension, the hazard ratio for developing ESRD was 41.2 (95% confidence interval [CI] 34.6 to 49.1) for patients with AKI and CKD relative to those without kidney disease, 13.0 (95% CI 10.6 to 16.0) for patients with AKI and without previous CKD, and 8.4 (95% CI 7.4 to 9.6) for patients with CKD and without AKI. In summary, elderly individuals with AKI, particularly those with previously diagnosed CKD, are at significantly increased risk for ESRD, suggesting that episodes of AKI may accelerate progression of renal disease. PMID:19020007

  10. Monoacylglycerol Lipase (MAGL) Inhibition Attenuates Acute Lung Injury in Mice

    PubMed Central

    Costola-de-Souza, Carolina; Ribeiro, Alison; Ferraz-de-Paula, Viviane; Calefi, Atilio Sersun; Aloia, Thiago Pinheiro Arrais; Gimenes-Júnior, João Antonio; de Almeida, Vinicius Izidio; Pinheiro, Milena Lobão; Palermo-Neto, João

    2013-01-01

    Endocannabinoid signaling is terminated by enzymatic hydrolysis, a process that, for 2-Arachidonoylglycerol (2-AG), is mediated by monoacylglycerol lipase (MAGL). The piperidine carbamate, 4-​nitrophenyl- ​4-​(dibenzo[d] [1,3]dioxol-​5-​yl (hydroxy) methyl) piperidine- 1-​carboxylate (JZL184), is a drug that inhibits MAGL and presents high potency and selectivity. Thus, JZL184 increases the levels of 2-AG, an endocannabinoid that acts on the CB1 and CB2 cannabinoid receptors. Here, we investigated the effects of MAGL inhibition, with a single dose (16 mg/kg, intraperitoneally (i.p.)) of JZL184, in a murine model of lipopolysaccharide (LPS) -induced acute lung injury (ALI) 6, 24 and 48 hours after the inflammatory insult. Treatment with JZL184 decreased the leukocyte migration into the lungs as well as the vascular permeability measured through the bronchoalveolar lavage fluid (BAL) and histological analysis. JZL184 also reduced the cytokine and chemokine levels in the BAL and adhesion molecule expression in the blood and BAL. The CB1 and CB2 receptors were considered involved in the anti-inflammatory effects of JZL184 because the AM281 selective CB1 receptor antagonist (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide) and the AM630 selective CB2 receptor antagonist ([6-​iodo-​2-​methyl-​1-​[2-​(4-​morpholinyl)ethyl]-​1H-​indol-​3-​yl](4-​methoxyphenyl)-​methanone) blocked the anti-inflammatory effects previously described for JZL184. It was concluded that MAGL inhibition, and consequently the increase in 2-AG levels, produced anti-inflammatory effects in a murine model of LPS-induced ALI, a finding that was considered a consequence of the activation of the CB1 and CB2 receptors. PMID:24204926

  11. Depressive Symptoms and Impaired Physical Function after Acute Lung Injury

    PubMed Central

    Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Dinglas, Victor D.; Shanholtz, Carl; Husain, Nadia; Dennison, Cheryl R.; Herridge, Margaret S.; Pronovost, Peter J.; Needham, Dale M.

    2012-01-01

    Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes. PMID:22161158

  12. Nonapnea Sleep Disorders and the Risk of Acute Kidney Injury

    PubMed Central

    Lin, Hugo You-Hsien; Chang, Kai-Ting; Chang, Yu-Han; Lu, Tzongshi; Liang, Chan-Jung; Wang, Dean-Chuan; Tsai, Jui-Hsiu; Hsu, Chung-Yao; Hung, Chi-Chih; Kuo, Mei-Chuan; Lin, Chang-Shen; Hwang, Shang-Jyh

    2016-01-01

    Abstract Nonapnea sleep disorders (NASDs) and associated problems, which are highly prevalent in patients with kidney diseases, are associated with unfavorable medical sequelae. Nonetheless, whether NASDs are associated with acute kidney injury (AKI) development has not been thoroughly analyzed. We examined the association between NASD and AKI. We conducted a population-based study by using 1,000,000 representative data from the Taiwan National Health Insurance Research Database for the period from January 1, 2000, to December 31, 2010. We studied the incidence and risk of AKI in 9178 newly diagnosed NASD patients compared with 27,534 people without NASD matched according to age, sex, index year, urbanization level, region of residence, and monthly income at a 1:3 ratio. The NASD cohort had an adjusted hazard ratio (hazard ratio [HR]; 95% confidence interval [CI] = 1.15–2.63) of subsequent AKI 1.74-fold higher than that of the control cohort. Older age and type 2 diabetes mellitus were significantly associated with an increased risk of AKI (P < 0.05). Among different types of NASDs, patients with insomnia had a 120% increased risk of developing AKI (95% CI = 1.38–3.51; P = 0.001), whereas patients with other sleep disorders had a 127% increased risk of subsequent AKI (95% CI = 1.07–4.80; P = 0.033). Men with NASDs were at a high risk of AKI (P < 0.05). This nationwide population-based cohort study provides evidence that patients with NASDs are at higher risk of developing AKI than people without NASDs. PMID:26986132

  13. Acanthoic acid ameliorates lipopolysaccharide-induced acute lung injury.

    PubMed

    Qiushi, Wang; Guanghua, Li; Guangquan, Xu

    2015-03-01

    Acanthoic acid, a pimaradiene diterpene isolated from Acanthopanax koreanum, has been reported to have anti-inflammatory activities. However, the effects of acanthoic acid on LPS-induced acute lung injury have not been reported. The purpose of this study was to investigate the protective effect of acanthoic acid on LPS-induced ALI and to clarify the possible anti-inflammatory mechanisms. In vivo, an LPS-induced ALI model in mice was used to assess the protective effects of acanthoic acid on ALI. Meanwhile, mouse alveolar macrophages MH-S were stimulated with LPS in the presence or absence of acanthoic acid. The expressions of TNF-α, IL-6 and IL-1β were measured by ELISA. LXRα and NF-κB expression were detected by Western blot analysis. The results showed that acanthoic acid downregulated LPS-induced TNF-α, IL-6 and IL-1β production in BALF. MPO activity and lung wet-to-dry ratio were also inhibited by acanthoic acid. In addition, acanthoic acid attenuated lung histopathologic changes. In vitro, acanthoic acid inhibited inflammatory cytokines TNF-α, IL-6 and IL-1β production and NF-κB activation in LPS-stimulated alveolar macrophages. Acanthoic acid was found to up-regulated the expression of LXRα. The inhibition of acanthoic acid on LPS-induced cytokines and NF-κB activation can be abolished by LXRα siRNA. In conclusion, our results suggested that the protective effect of acanthoic acid on LPS-induced ALI was due to its ability to activate LXRα, thereby inhibiting LPS-induced inflammatory response. PMID:25620130

  14. Pentoxifylline in ischemia-induced acute kidney injury in rats.

    PubMed

    Okumura, Alice S; Rodrigues, Luiz Erlon; Martinelli, Reinaldo

    2009-01-01

    Ischemia is an important cause of acute kidney injury (AKI). Pentoxifylline has been shown to improve tissue oxygenation and endothelial function and inhibit proinflammatory cytokine production. The aim of this study was to evaluate a possible renal protective effect of pentoxifylline against ischemia by measuring mitochondrial respiratory metabolism as an index of cell damage. Rats were submitted to right nephrectomy. The left kidney was submitted to ischemia by clamping the renal artery for 45 minutes. Immediately after release of the clamp, 1 mL of a solution containing 20 mg of pentoxifylline/mL was injected intravenously, while a control group received 1 mL of normal saline intravenously. Five minutes after the injection, the left kidney was removed, homogenized, and subjected to refrigerated differential centrifugation. Mitochondrial respiratory metabolism was measured polarographically. The mitochondria isolated from the kidneys of saline-treated rats had an endogenous respiration of 9.20 +/- 1.0 etamol O(2)/mg protein/min compared to 8.9 +/- 1.4 etamol O(2)/mg protein/min in the pentoxifylline-treated rats (p > 0.05). When stimulated by sodium succinate, the respiratory metabolism increased in a similar fashion in both groups of animals: 17.9 +/- 2.3 and 18.1 +/- 2.1 etamol O(2)/mg protein/min in the untreated and pentoxifylline-treated groups, respectively (p > 0.05). In the present study, pentoxifylline was not found to exert any protective effect on the kidney. It is possible that at the time of pentoxifylline administration, the mitochondria had already been damaged by the process of ischemia, and its effect may have been insufficient to reverse cell damage. PMID:19925292

  15. Sex, Race, and the Development of Acute Lung Injury

    PubMed Central

    Lemos-Filho, Luciano B.; Mikkelsen, Mark E.; Martin, Greg S.; Dabbagh, Ousama; Adesanya, Adebola; Gentile, Nina; Esper, Annette; Gajic, Ognjen

    2013-01-01

    Background: Prior studies suggest that mortality differs by sex and race in patients who develop acute lung injury (ALI). Whether differences in presentation account for these disparities remains unclear. We sought to determine whether sexual and racial differences exist in the rate of ALI development and ALI-related mortality after accounting for differences in clinical presentations. Methods: This was a multicenter, observational cohort study of 5,201 patients at risk for ALI. Multivariable logistic regression with adjustment for center-level effects was used to adjust for potential covariates. Results: The incidence of ALI development was 5.9%; in-hospital mortality was 5.0% for the entire cohort, and 24.4% for those patients who developed ALI. Men were more likely to develop ALI compared to women (6.9% vs 4.7%, P < .001) and had a nonsignificant increase in mortality when ALI developed (27.6% vs 18.5%, P = .08). However, after adjustment for baseline imbalances between sexes these differences were no longer significant. Black patients, compared to white patients, presented more frequently with pneumonia, sepsis, or shock and had higher severity of illness. Black patients were less likely to develop ALI than whites (4.5% vs. 6.5%, P = .014), and this association remained statistically significant after adjusting for differences in presentation (OR, 0.66; 95 % CI, 0.45-0.96). Conclusions: Sex and race differences exist in the clinical presentation of patients at risk of developing ALI. After accounting for differences in presentation, there was no sex difference in ALI development and outcome. Black patients were less likely to develop ALI despite increased severity of illness on presentation. PMID:23117155

  16. Pediatric reference ranges for acute kidney injury biomarkers

    PubMed Central

    Nehus, Edward; Haffner, Christopher; Ma, Qing; Devarajan, Prasad

    2015-01-01

    Background Novel urinary biomarkers are useful for the prediction of acute kidney injury (AKI). Most promising are the urine markers NGAL, IL-18, KIM-1, and LFABP. Each of these has shown considerable promise diagnosing AKI earlier than serum creatinine (Scr) using disease controls. We set out to determine reference levels of these markers in a healthy pediatric population. Methods Urine was collected from 368 healthy children and assayed for NGAL, IL-18, KIM-1, and LFABP using commercially available kits or assay materials. Analysis of biomarkers by linear regression and according to age groups (3–<5 years; 5–<10; 10–<15; 15–<18) was performed to determine if biomarker levels differed with age and gender. Results Median values were: NGAL (6.6 ng/ml; IQR 2.8–17), IL-18 (21.6 pg/ml; IQR 13.6–32.9), KIM-1 (410 pg/ml; IQR 226–703), LFABP (3.4 ng/ml; IQR 1.6–6.0). Significant gender differences were found with NGAL and IL-18 and significant age differences were found with all markers. 95th percentile values for each marker varied with age and gender greater than median values. Conclusions This is the largest pediatric reference range study for the urinary measurement of NGAL, IL-18, KIM-1, and LFABP and highlights age and gender differences in these markers. This information is essential for rational interpretation of studies and clinical trials utilizing these emerging AKI biomarkers. PMID:25348707

  17. Translational biomarkers of acetaminophen-induced acute liver injury.

    PubMed

    Beger, Richard D; Bhattacharyya, Sudeepa; Yang, Xi; Gill, Pritmohinder S; Schnackenberg, Laura K; Sun, Jinchun; James, Laura P

    2015-09-01

    Acetaminophen (APAP) is a commonly used analgesic drug that can cause liver injury, liver necrosis and liver failure. APAP-induced liver injury is associated with glutathione depletion, the formation of APAP protein adducts, the generation of reactive oxygen and nitrogen species and mitochondrial injury. The systems biology omics technologies (transcriptomics, proteomics and metabolomics) have been used to discover potential translational biomarkers of liver injury. The following review provides a summary of the systems biology discovery process, analytical validation of biomarkers and translation of omics biomarkers from the nonclinical to clinical setting in APAP-induced liver injury. PMID:25983262

  18. Cell elimination as a strategy for repair in acute spinal cord injury.

    PubMed

    Kalderon, Nurit

    2005-01-01

    Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later stages of wound healing (the third week after injury) triggering chronic inflammation and progressive tissue decay that is the characteristic pathology of spinal cord injury. Specific cell elimination within a critical time window after injury can lead to repair in the acutely injured spinal cord. Cell proliferation events can be manipulated/modified by x-irradiation. Clinically, numerous radiation protocols (i.e., radiation therapy) have been developed that specifically eliminate the rapidly dividing cells without causing any noticeable/significant damage to the tissue as a whole. Radiation therapy when applied within the critical time window after injury prevents the onset of chronic inflammation thus leading to repair of structure and function. Various aspects of the development of this cell-elimination strategy for repair in acute spinal cord injury by utilizing radiation therapy are being reviewed. Topics reviewed here: identifying the window of opportunity; and the beneficial repair effects of radiation therapy in a transection injury model and in a model relevant to human injury, the contusion injury model. The possible involvement of cellular components of the blood-spinal cord barrier as the trigger of chronic inflammation and/or target of the radiation therapy is discussed. PMID:15853680

  19. Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

    PubMed Central

    Guo, Rui; Lin, Bin; Pan, Jing Fei; Liong, Emily C.; Xu, Ai Min; Youdim, Moussa; Fung, Man Lung; So, Kwok Fai; Tipoe, George L.

    2016-01-01

    Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury. PMID:27580936

  20. Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy.

    PubMed

    Guo, Rui; Lin, Bin; Pan, Jing Fei; Liong, Emily C; Xu, Ai Min; Youdim, Moussa; Fung, Man Lung; So, Kwok Fai; Tipoe, George L

    2016-01-01

    Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury. PMID:27580936

  1. Neutralization of ADAM8 ameliorates liver injury and accelerates liver repair in carbon tetrachloride-induced acute liver injury.

    PubMed

    Li, San-Qiang; Zhu, Sha; Wan, Xue-Dong; Xu, Zheng-Shun; Ma, Zhao

    2014-04-01

    Although some studies have described the function of ADAM8 (a disintegrin and metalloprotease 8) related with rheumatoid arthritis, cancer and asthma, etc., the concrete role of ADAM8 in acute liver injury is still unknown. So mice respectively received anti-ADAM8 monoclonal antibody (mAb) of 100 μg/100 μl, 200 μg/100 μl or 300 μg/100 μl in PBS or PBS pre-injection. Then acute liver injury was induced in the mice by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl₄). Serum AST and ALT level, Haematoxylin-eosin (H&E) staining, the expression level of vascular endothelial growth factor (VEGF), cytochrome P450 1A2 (CYP1A2) and proliferating cell nuclear antigen (PCNA) were detected in the mice after CCl4 administration. Our results showed that anti-ADAM8 mAb pre-injection could effectively lower AST and ALT levels (P < 0.05 or P < 0.01) and reduce liver injury (P < 0.05 or P <0.01), induce the expression of VEGF, CYP1A2 and PCNA (P <0.05 or P < 0.01) in dose-dependent manner compared with the control mice which received PBS pre-injection. In summary, our study suggested that ADAM8 might promote liver injury by inhibiting the proliferation of hepatocytes, angiogenesis and affecting the metabolism function of liver during acute liver injury induced by CCl₄. Anti-ADAM8 mAb injection might be suitable as a potential method for acute liver injury therapy. PMID:24646716

  2. Molecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord Injury.

    PubMed

    Thakore, Nakul P; Samantaray, Supriti; Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A; Cox, April; Krause, James; Banik, Naren L

    2016-02-01

    To clarify the molecular changes of sublesional muscle in the acute phase of spinal cord injury (SCI), a moderately severe injury (40 g cm) was induced in the spinal cord (T10 vertebral level) of adult male Sprague-Dawley rats (injury) and compared with sham (laminectomy only). Rats were sacrificed at 48 h (acute) post injury, and gastrocnemius muscles were excised. Morphological examination revealed no significant changes in the muscle fiber diameter between the sham and injury rats. Western blot analyses performed on the visibly red, central portion of the gastrocnemius muscle showed significantly higher expression of muscle specific E3 ubiquitin ligases (muscle ring finger-1 and muscle atrophy f-box) and significantly lower expression of phosphorylated Akt-1/2/3 in the injury group compared to the sham group. Cyclooxygenase 2, tumor necrosis factor alpha (TNF-α), and caspase-1, also had a significantly higher expression in the injury group; although, the mRNA levels of TNF-α and IL-6 did not show any significant difference between the sham and injury groups. These results suggest activation of protein degradation, deactivation of protein synthesis, and development of inflammatory reaction occurring in the sublesional muscles in the acute phase of SCI before overt muscle atrophy is seen. PMID:26290268

  3. [Acute Kidney Injury, Type - 3 cardiorenal syndrome, Biomarkers, Renal Replacement Therapy].

    PubMed

    Di Lullo, Luca; Bellasi, Antonio; Barbera, Vincenzo; Cozzolino, Mario; Russo, Domenico; De Pascalis, Antonio; Santoboni, Francesca; Villani, Annalisa; De Rosa, Silvia; Colafelice, Marco; Russo, Luigi; Ronco, Claudio

    2016-01-01

    Cardiovascular disease and major cardiovascular events represent main cause of death in both acute and chronic kidney disease patients. Kidney and heart failure are common and frequently co-exist This organ-organ interaction, also called organ cross-talk, leads to well-known definition of cardiorenal syndrome (CRS). Here we will describe cardiovascular involvement in patients with acute kidney injury (AKI). Also known as Type-3 CRS or acute reno-cardiac CRS, it occurs when AKI contributes and/or precipitates development of acute cardiac injury. AKI may directly or indirectly produces an acute cardiac event and it can be associated with volume overload, metabolic acidosis and electrolytes disorders such as hyperkalemia and hypocalcemia, coronary artery disease, left ventricular dysfunction and fibrosis which has been also described in patients with AKI with the consequence of direct negative effects on cardiac performance. PMID:27374388

  4. Functional genomics of chlorine-induced acute lung injury in mice.

    PubMed

    Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A; Dopico, Richard A; Di, Y Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J; Kaminski, Naftali; You, Ming; Prows, Daniel R

    2010-07-01

    Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury. PMID:20601635

  5. Asialoerythropoietin ameliorates bleomycin-induced acute lung injury in rabbits by reducing inflammation.

    PubMed

    Sonoda, Akinaga; Nitta, Norihisa; Tsuchiya, Keiko; Otani, Hideji; Watanabe, Shobu; Mukaisho, Kenichi; Tomozawa, Yuki; Nagatani, Yukihiro; Ohta, Shinichi; Takahashi, Masashi; Murata, Kiyoshi

    2014-11-01

    Acute lung injury, a critical illness characterized by acute respiratory failure with bilateral pulmonary infiltrates, remains unresponsive to current treatments. The condition involves injury to the alveolar capillary barrier, neutrophil accumulation and the induction of proinflammatory cytokines followed by lung fibrosis. In the present study, a rabbit model of bleomycin-induced acute lung injury was established to examine the effects of asialoerythropoietin (AEP), an agent with tissue-protective activities, on pulmonary inflammation. Six Japanese white rabbits were randomly divided into two equal groups. Acute lung injury was induced in all rabbits by intratracheally injecting bleomycin. The control group was injected with bleomycin only; the experimental (AEP) group was injected intravenously with AEP (80 μg/kg) prior to the bleomycin injection. Computed tomography (CT) studies were performed seven days later. The CT inflammatory scores of areas exhibiting abnormal density and the pathological inflammatory scores were recorded as a ratio on a 7×7 mm grid. The CT and pathological inflammatory scores were significantly different between the control and AEP groups [122±10 and 16.3±1.5 (controls) vs. 71±8.5 and 9.7±1.4 (AEP), respectively; P<0.01]. Thus, the present study revealed that AEP prevents bleomycin-induced acute lung injury in rabbits. PMID:25289037

  6. Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

    2013-05-01

    Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

  7. Acute kidney injury in critically ill patients with lung disease: kidney-lung crosstalk

    PubMed Central

    de Abreu, Krasnalhia Lívia Soares; da Silva Junior, Geraldo Bezerra; Muniz, Thalita Diógenes; Barreto, Adller Gonçalves Costa; Lima, Rafael Siqueira Athayde; Holanda, Marcelo Alcântara; Pereira, Eanes Delgado Barros; Libório, Alexandre Braga; Daher, Elizabeth de Francesco

    2013-01-01

    Objective To examine the factors associated with acute kidney injury and outcome in patients with lung disease. Methods A prospective study was conducted with 100 consecutive patients admitted to a respiratory intensive care unit in Fortaleza (CE), Brazil. The risk factors for acute kidney injury and mortality were investigated in a group of patients with lung diseases. Results The mean age of the study population was 57 years, and 50% were male. The incidence of acute kidney injury was higher in patients with PaO2/FiO2<200 mmHg (54% versus 23.7%; p=0.02). Death was observed in 40 cases and the rate of mortality of the acute kidney injury group was higher (62.8% versus 27.6%; p=0.01). The independent factor that was found to be associated with acute kidney injury was PaO2/FiO2<200 mmHg (p=0.01), and the independent risk factors for death were PEEP at admission (OR: 3.6; 95%CI: 1.3-9.6; p=0.009) and need for hemodialysis (OR: 7.9; 95%CI: 2.2-28.3; p=0.001). Conclusion There was a higher mortality rate in the acute kidney injury group. Increased mortality was associated with mechanical ventilation, high PEEP, urea and need for dialysis. Further studies must be performed to better establish the relationship between kidney and lung injury and its impact on patient outcome. PMID:23917978

  8. Preventive Effects of Eccentric Training on Acute Hamstring Muscle Injury in Professional Baseball

    PubMed Central

    Seagrave, Richard A.; Perez, Luis; McQueeney, Sean; Toby, E. Bruce; Key, Vincent; Nelson, Joshua D.

    2014-01-01

    Background: Hamstring injuries are the second most common injury causing missed days in professional baseball field players. Recent studies have shown the preventive benefit of eccentric conditioning on the hamstring muscle group in injury prevention. Specifically, Nordic-type exercises have been shown to decrease the incidence of acute hamstring injuries in professional athletes. Purpose: This was a prospective study performed in coordination with a single Major League Baseball (MLB) organization (major and minor league teams) that targeted the effects of Nordic exercises on the incidence of acute hamstring injuries in the professional-level baseball player. Study Design: Prospective cohort study; Level of evidence, 2. Methods: The daily workouts of 283 professional baseball players throughout all levels of a single MLB organization were prospectively recorded. The intervention group participated in the Nordic exercise program and was compared with a randomly selected control group of professional athletes within the organization not participating in the exercise program. The incidence of hamstring injuries in both groups was compared, and the total number of days missed due to injury was compared with the 2 previous seasons. Results: There were 10 hamstring injuries that occurred during the 2012 season among the 283 professional athletes that required removal from play. There were no injuries that occurred in the intervention group (n = 65, 0.00%; P = .0381). The number needed to treat (NNT) to prevent 1 hamstring injury was 11.3. The average repetitions per week of the injured group were assessed at multiple time points (2, 4, 6, and total weeks) prior to injury. There were significantly fewer repetitions per week performed in the injured group at all time points compared with overall average repetitions per week in the noninjured group (P = .0459, .0127, .0164, and .0299, respectively). After beginning the Nordic exercise program, there were 136 total days

  9. Nilotinib ameliorates lipopolysaccharide-induced acute lung injury in rats

    SciTech Connect

    El-Agamy, Dina S.

    2011-06-01

    The present study aimed to investigate the effect of the new tyrosine kinase inhibitor, nilotinib on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and explore its possible mechanisms. Male Sprague-Dawley rats were given nilotinib (10 mg/kg) by oral gavage twice daily for 1 week prior to exposure to aerosolized LPS. At 24 h after LPS exposure, bronchoalveolar lavage fluid (BALF) samples and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathological changes in lungs. Malondialdehyde (MDA) content, superoxidase dismutase (SOD) and reduced glutathione (GSH) activities as well as nitrite/nitrate (NO{sub 2}{sup -}/NO{sub 3}{sup -}) levels were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-{alpha} (TNF-{alpha}), transforming growth factor-{beta}{sub 1} (TGF-{beta}{sub 1}) and inducible nitric oxide synthase (iNOS) were determined in lung tissues. Treatment with nilotinib prior to LPS exposure significantly attenuated the LPS-induced pulmonary edema, as it significantly decreased lung W/D ratio, protein concentration and the accumulation of the inflammatory cells in the BALF. This was supported by the histopathological examination which revealed marked attenuation of LPS-induced ALI in nilotinib treated rats. In addition, nilotinib significantly increased SOD and GSH activities with significant decrease in MDA content in the lung. Nilotinib also reduced LPS mediated overproduction of pulmonary NO{sub 2}{sup -}/NO{sub 3}{sup -} levels. Importantly, nilotinib caused down-regulation of the inflammatory cytokines TNF-{alpha}, TGF-{beta}{sub 1} and iNOS levels in the lung. Taken together, these results demonstrate the protective effects of nilotinib against the LPS-induced ALI. This effect can be attributed to nilotinib ability to counteract the inflammatory cells

  10. A low energy paediatric clavicle fracture associated with acute brachial plexus injury and subclavian artery compression.

    PubMed

    Gill, I; Quayle, J; Fox, M

    2013-03-01

    Paediatric clavicle fractures are common injuries presenting to orthopaedic surgeons. The majority of these represent midshaft low energy fractures, which in the vast majority of cases are treated non-operatively and recover rapidly. The main indications to consider operative intervention include high energy of injury, >2 cm shortening, open fractures and associated vascular or neurological injuries. Brachial plexus (BP) injuries are uncommon with variable outcomes. They often result from high energy motorcycle related accidents with potentially fatal associated injuries such as vascular disruption. Their management is complex, requiring expertise, and they are therefore usually managed in supraregional centres. We present a unique case of a low energy midshaft clavicle fracture in a paediatric patient in whom there was an acute BP injury and subclavian artery compression that has not been described previously. PMID:23484977

  11. What has been learnt from P/V curves in patients with acute lung injury/acute respiratory distress syndrome.

    PubMed

    Maggiore, S M; Richard, J C; Brochard, L

    2003-08-01

    Mechanical impairment of the respiratory system was recognised soon after the description of acute respiratory distress syndrome. The analysis of the pressure/volume (P/V) curve of the respiratory system contributed a lot to the understanding of the pathophysiology of acute lung injury and formed the basis for lung protection. The lower and upper inflection points were regarded as points of interest to avoid cyclic derecruitment and overdistension and to optimise ventilatory settings. However, because of the heterogeneity of lung injury, reducing the mechanical properties of the whole respiratory system to a single curve is a schematic approach, which makes interpretation difficult. New data suggest that alveolar re-inflation occurs along the whole P/V curve that can, therefore, be considered as a recruitment curve. The lower inflection point has no relationship with alveolar opening and closure and does not indicate the positive end-expiratory pressure needed to prevent alveolar collapse. The shape of the P/V curve gives information about the extension and the homogeneity of lung injury, indicating the possibility of lung recruitment. The upper inflection point, classically seen as the beginning of overdistension, may also indicate the end of recruitment. The pressure/volume curve offers the unique opportunity of evaluating alveolar recruitment/derecruitment at the bedside that can be helpful for the identification of optimal ventilatory settings and makes the curve a valuable tool for the ventilatory management of acute lung injury. PMID:12945997

  12. Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer

    PubMed Central

    van den Eijnde, Wilbert A.J.; Peppelman, Malou; Lamers, Edwin A.D.; van de Kerkhof, Peter C.M.; van Erp, Piet E.J.

    2014-01-01

    Background: Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports. Purpose: To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact. Study Design: Systematic review; Level of evidence, 4. Methods: The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact. Results: The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries. Conclusion: The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin. PMID:26535330

  13. Monitor lizard bite-induced acute kidney injury--a case report.

    PubMed

    Vikrant, Sanjay; Verma, Balbir Singh

    2014-04-01

    Envenomations by venomous lizards are rare. Monitor lizard bite-induced acute kidney injury (AKI) is a previously unreported complication in humans. A 55-year-old female was bitten on her right leg during farming activity by a monitor lizard (Varanus bengalensis). The patient experienced severe local pain and bleeding from the wound, coagulopathy, hemolysis, rhabdomyolysis, sepsis, and AKI. Patient was treated with supportive care and peritoneal dialysis but succumbed to a sudden cardiac arrest. Post mortem kidney biopsy revealed pigment induced-acute tubular injury. AKI after monitor lizard envenomation is caused by acute tubular injury in the setting of intravascular hemolysis, rhabdomyolysis and sepsis. Coagulopathy and direct nephrotoxicity may be the other contributory factors in causing AKI. PMID:24341640

  14. CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis.

    PubMed

    Wang, Chao-Yung; Hsieh, Ming-Jer; Hsieh, I-Chang; Shie, Shian-Sen; Ho, Ming-Yun; Yeh, Jih-Kai; Tsai, Ming-Lung; Yang, Chia-Hung; Hung, Kuo-Chun; Wang, Chun-Chieh; Wen, Ming-Shien

    2016-09-16

    Polymicrobial sepsis is a potentially fatal condition and a significant burden on health care systems. Acute lung injury is the most common complication of sepsis and results in high mortality. However, there has been no recent significant progress in the treatment of sepsis or acute lung injury induced by sepsis. Here we show that mice deficient in the circadian protein CLOCK had better survival than wild-type mice after induction of polymicrobial sepsis by cecal ligation and puncture. Inflammatory cytokine production was attenuated and bacterial clearance was improved in CLOCK-deficient mice. Moreover, acute lung injury after induction of sepsis was significantly decreased in CLOCK-deficient mice. Genome-wide profiling analysis showed that inhibin signaling was reduced in CLOCK-deficient mice. These data establish the importance of circadian CLOCK-inhibin signaling in sepsis, which may have potential therapeutic implications. PMID:27520377

  15. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

    PubMed Central

    Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

  16. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

    PubMed

    Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

  17. Successful Mitigation of Delayed Intestinal Radiation Injury Using Pravastatin is not Associated with Acute Injury Improvement or Tumor Protection

    SciTech Connect

    Haydont, Valerie; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine |. E-mail: vozenin@igr.fr

    2007-08-01

    Purpose: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. Methods and Materials: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. Results: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury. Conclusion: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible.

  18. Time profile of oxidative stress and neutrophil activation in ovine acute lung injury and sepsis.

    PubMed

    Lange, Matthias; Szabo, Csaba; Traber, Daniel L; Horvath, Eszter; Hamahata, Atsumori; Nakano, Yoshimitsu; Traber, Lillian D; Cox, Robert A; Schmalstieg, Frank C; Herndon, David N; Enkhbaatar, Perenlei

    2012-05-01

    The formation of oxidative stress in the lung and activation of neutrophils are major determinants in the development of respiratory failure after acute lung injury and sepsis. However, the time changes of these pathogenic factors have not been sufficiently described. Twenty-four chronically instrumented sheep were subjected to cotton smoke inhalation injury and instillation of live Pseudomonas aeruginosa into both lungs. The sheep were euthanized at 4, 8, 12, 18, and 24 h after injury. Additional sheep received sham injury and were euthanized after 24 h. Pulmonary function was assessed by determination of oxygenation index and pulmonary shunt fraction. In addition, lung tissue was harvested at the respective time points for the measurement of malondialdehyde, interleukin 6, poly(ADP ribose), myeloperoxidase, and alveolar polymorphonuclear neutrophil score. The injury induced severe respiratory failure that was associated with an early increase in lipid peroxidation and interleukin 6 expression. The injury further led to an increase in poly(ADP ribose) activity that reached its peak at 12 h after injury and declined afterward. In addition, progressive increases in markers of neutrophil accumulation in the lung were observed. The peak of neutrophil accumulation in the lung was associated with a severe depletion of circulating neutrophils. The results from our model may enhance the understanding of the pathophysiological alterations after acute lung injury and sepsis and thus be useful in exploring therapeutic interventions directed at modifying the expression or activation of inflammatory mediators. PMID:22266977

  19. [Arthroscopically assisted techniques for treatment of acute and chronic acromioclavicular joint injuries].

    PubMed

    Braun, S; Imhoff, A B; Martetschläger, F

    2015-05-01

    Acute and chronic acromioclavicular (AC) joint dislocation is frequently encountered in the routine clinical practice. This injury can lead to significant impairment of shoulder girdle function. Therapy based on the severity of injury is recommended to re-establish correct shoulder function. The static radiographic Rockwood classification is used to define the degree of dislocation but the clinical aspects and functional x-ray imaging of horizontal AC joint instability should also be considered for selection of the appropriate procedure. Rockwood grades I and II injuries are treated non-operatively with early functional exercise. The approach for Rockwood grade III injuries should be individual and patient-specific, with non-surgical procedures for low functional requirement patients with a high risk for surgical interventions. For patients with high demands on shoulder function surgery is recommended. A detailed diagnostic assessment frequently reveals Rockwood grade III injuries to be type IV injuries. Rockwood types IV and V AC joint dislocations require surgery for sustained stability. Treatment of acute injuries is recommended within 1-3 weeks after trauma but there is no clear evidence of a cut-off for the presence of chronic injuries. Various surgical techniques have been described in the literature. This article presents an arthroscopically assisted technique that addresses both vertical and horizontal instability of the AC joint. PMID:25964020

  20. Acute liver injury with severe coagulopathy in marasmus caused by a somatic delusional disorder.

    PubMed

    Stein, Lance L; Jesudian, Arun B

    2011-01-01

    Marasmus is a severe form of protein-calorie malnutrition characterized by the depletion of fat stores, muscle wasting, and the lack of edema. In developed countries, marasmus is often the result of anorexia nervosa. Abnormal transaminases with liver synthetic dysfunction have rarely been reported with anorexia nervosa. To our knowledge, we report the first detailed case of acute liver injury with severe coagulopathy (INR > 1.5) in a patient with marasmus due to self-induced calorie restriction caused by a somatic delusional disorder. This case highlights the severity of liver injury that may occur with significant weight loss from self-induced calorie restriction and the rapid normalization of this injury with treatment. It is important for clinicians to be aware of patterns of acute liver injury in patients with severe protein-calorie malnutrition, regardless of the underlying cause. PMID:25954537

  1. Unusual case of acute tracheal injury complicated by application of positive end expiratory pressure (PEEP).

    PubMed

    Farooqui, Asif Masroor; Mbarushimana, Simon; Faheem, Mohammad

    2014-01-01

    Blunt neck trauma can be caused by a variety of injuries such as deceleration, road traffic accidents and crush injuries. The worst scenario is airway rupture. We report an unusual case of acute tracheal injury in a 34-year-old Irish man who presented with a history of strangulation while working with a tractor. On arrival, he had one episode of mild haemoptysis and reported pain around the base of the neck and voice hoarseness. His chest X-ray revealed pneumopericardium and CT of thorax showed airway oedema. After elective intubation, positive end-expiratory pressure (PEEP) of 5 cm H2O caused deterioration in his clinical condition with increasing surgical emphysema and rise of carbon dioxide partial pressure (PaCO2), which was completely reversed after stopping PEEP. This case shows how PEEP and intermittent positive pressure ventilation can worsen air leak and compromise stability in patients with acute tracheal injury. PMID:25398917

  2. Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier*

    PubMed Central

    Zhang, Xi-ping; Zhang, Jie; Song, Qiao-ling; Chen, Han-qin

    2007-01-01

    Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP’s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP’s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP. PMID:18257123

  3. Acute liver injury associated with a newer formulation of the herbal weight loss supplement Hydroxycut.

    PubMed

    Araujo, James L; Worman, Howard J

    2015-01-01

    Despite the widespread use of herbal and dietary supplements (HDS), serious cases of hepatotoxicity have been reported. The popular herbal weight loss supplement, Hydroxycut, has previously been implicated in acute liver injury. Since its introduction, Hydroxycut has undergone successive transformations in its formulation; yet, cases of liver injury have remained an ongoing problem. We report a case of a 41-year-old Hispanic man who developed acute hepatocellular liver injury with associated nausea, vomiting, jaundice, fatigue and asterixis attributed to the use of a newer formulation of Hydroxycut, SX-7 Clean Sensory. The patient required hospitalisation and improved with supportive therapy. Despite successive transformations in its formulation, potential liver injury appears to remain an ongoing problem with Hydroxycut. Our case illustrates the importance of obtaining a thorough medication history, including HDS, regardless of new or reformulated product marketing efforts. PMID:25948859

  4. CYP1A2 polymorphism in Chinese patients with acute liver injury induced by Polygonum multiflorum.

    PubMed

    Ma, K F; Zhang, X G; Jia, H Y

    2014-01-01

    The objective of this study was to evaluate the genotype and allelic frequencies of CYP1A2 in Chinese patients with acute liver injury induced by Polygonum multiflorum. We examined the clinical mechanism of acute liver injury induced by P. multiflorum. According to the diagnostic criteria for drug-induced liver injury (DILI), 43 cases of P. multiflorum-induced liver injury admitted to the First Affiliated Hospital, Zhejiang University were identified between January 2008 and December 2012. An additional 43 control subjects were also chosen. Several alleles, including 1C, 1F, 2, 7, 9, and 11 of CYP1A2 were amplified from genomic DNA and sequenced. We used the chi-square test to determine whether CYP1A2 allele polymorphisms are associated with acute liver injury induced by P. multiflorum. The frequency of the CYP1A2 1C allele was 46.5% in P. multiflorum-induced DILI patients, which was significantly different from the frequency of 27.9% observed in healthy subjects. The frequency of the CYP1A2 1F allele was 63.9% in P. multiflorum-induced DILI patients, compared to 57.0% in healthy controls; the difference was not significant. The allelic frequencies of CYP1A2 2, CYP1A2 7, CYP1A2 9, and CYP1A2 11 were too low to be detected. The frequency of the CYP1A2 1C mutation in Chinese patients with P. multiflorum-induced acute liver injury differed from that in healthy Chinese people, indicating that CYP1A2 1C is probably related to metabolism of P. multiflorum, which is followed by acute liver injury. PMID:25117321

  5. Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury.

    PubMed

    Liu, Yong; Zhou, Dan; Long, Fei-Wu; Chen, Ke-Ling; Yang, Hong-Wei; Lv, Zhao-Yin; Zhou, Bin; Peng, Zhi-Hai; Sun, Xiao-Feng; Li, Yuan; Zhou, Zong-Guang

    2016-03-01

    Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-κB activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-α, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-κB activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-κB activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis. PMID:26702138

  6. Neurogenic Fever after Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review

    PubMed Central

    Savage, Katherine E.; Oleson, Christina V.; Schroeder, Gregory D.; Sidhu, Gursukhman S.; Vaccaro, Alexander R.

    2016-01-01

    Study Design  Systematic review. Objective  To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI). Methods  A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained. Results  The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. The incidence of fever of unknown origin (neurogenic fever) ranged from 2.6 to 27.8% with a mean incidence of 8.0% and a median incidence of 4.7%. Cervical and thoracic spinal injuries were more commonly associated with fever than lumbar injuries. In addition, complete injuries had a higher incidence of fever than incomplete injuries. The pathogenesis of neurogenic fever after acute SCI is not thoroughly understood. Conclusion  Neurogenic fevers are relatively common following an acute SCI; however, there is little in the scientific literature to help physicians prevent or treat this condition. The paucity of research underscored by this review demonstrates the need for further studies with larger sample sizes, focusing on incidence rate, clinical outcomes, and pathogenesis of neurogenic fever following acute traumatic SCI. PMID:27556002

  7. The serpentine path to a novel mechanism-based inhibitor of acute inflammatory lung injury

    PubMed Central

    2014-01-01

    The Comroe lecture on which this review is based described my research path during the past 45 years, beginning with studies of oxidant stress (hyperoxia) and eventuating in the discovery of a synthetic inhibitor of phospholipase A2 activity (called MJ33) that prevents acute lung injury in mice exposed to lipopolysaccharide. In between were studies of lung ischemia, lung surfactant metabolism, the protein peroxiredoxin 6 and its phospholipase A2 activity, and mechanisms for NADPH oxidase activation. These seemingly unrelated research activities provided the nexus for identification of a novel target and a potentially novel therapeutic agent for prevention or treatment of acute lung injury. PMID:24744383

  8. Therapeutic translation in acute kidney injury: the epithelial/endothelial axis

    PubMed Central

    Molitoris, Bruce A.

    2014-01-01

    Acute kidney injury (AKI) remains a major clinical event with rising incidence, severity, and cost; it now has a morbidity and mortality exceeding acute myocardial infarction. There is also a documented conversion to and acceleration of chronic kidney disease to end-stage renal disease. The multifactorial nature of AKI etiologies and pathophysiology and the lack of diagnostic techniques have hindered translation of preclinical success. An evolving understanding of epithelial, endothelial, and inflammatory cell interactions and individualization of care will result in the eventual development of effective therapeutic strategies. This review focuses on epithelial and endothelial injury mediators, interactions, and targets for therapy. PMID:24892710

  9. Salvianolic Acids Attenuate Rat Hippocampal Injury after Acute CO Poisoning by Improving Blood Flow Properties

    PubMed Central

    Guan, Li; Zhang, Yan-Lin; Li, Zong-Yang; Zhu, Ming-Xia; Yao, Wei-Juan; Zhao, Jin-Yuan

    2015-01-01

    Carbon monoxide (CO) poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP) occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA) on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct), plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA) levels in red blood cells (RBCs). These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning. PMID:25705671

  10. Amniotic Fluid Stem Cells from EGFP Transgenic Mice Attenuate Hyperoxia-Induced Acute Lung Injury

    PubMed Central

    Lai, Cheng-Wei; Yen, Chih-Ching; Lee, Kun-Hsiung; Wu, Shinn-Chih; Chen, Chuan-Mu

    2013-01-01

    High concentrations of oxygen aggravate the severity of lung injury in patients requiring mechanical ventilation. Although mesenchymal stem cells have been shown to effectively attenuate various injured tissues, there is limited information regarding a role for amniotic fluid stem cells (AFSCs) in treating acute lung injury. We hypothesized that intravenous delivery of AFSCs would attenuate lung injury in an experimental model of hyperoxia-induced lung injury. AFSCs were isolated from EGFP transgenic mice. The in vitro differentiation, surface markers, and migration of the AFSCs were assessed by specific staining, flow cytometry, and a co-culture system, respectively. The in vivo therapeutic potential of AFSCs was evaluated in a model of acute hyperoxia-induced lung injury in mice. The administration of AFSCs significantly reduced the hyperoxia-induced pulmonary inflammation, as reflected by significant reductions in lung wet/dry ratio, neutrophil counts, and the level of apoptosis, as well as reducing the levels of inflammatory cytokine (IL-1β, IL-6, and TNF-α) and early-stage fibrosis in lung tissues. Moreover, EGFP-expressing AFSCs were detected and engrafted into a peripheral lung epithelial cell lineage by fluorescence microscopy and DAPI stain. Intravenous administration of AFSCs may offer a new therapeutic strategy for acute lung injury (ALI), for which efficient treatments are currently unavailable. PMID:24040409

  11. The Role of Magnetic Resonance Imaging in the Management of Acute Spinal Cord Injury

    PubMed Central

    Bozzo, Anthony; Marcoux, Judith; Radhakrishna, Mohan; Pelletier, Julie

    2011-01-01

    Abstract Magnetic resonance imaging (MRI) has become the gold standard for imaging neurological tissues including the spinal cord. The use of MRI for imaging in the acute management of patients with spinal cord injury has increased significantly. This paper used a vigorous literature review with Downs and Black scoring, followed by a Delphi vote on the main conclusions. MRI is strongly recommended for the prognostication of acute spinal cord injury. The sagittal T2 sequence was particularly found to be of value. Four prognostication patterns were found to be predictive of neurological outcome (normal, single-level edema, multi-level edema, and mixed hemorrhage and edema). It is recommended that MRI be used to direct clinical decision making. MRI has a role in clearance, the ruling out of injury, of the cervical spine in the obtunded patient only if there is abnormality of the neurological exam. Patients with cervical spinal cord injuries have an increased risk of vertebral artery injuries but the literature does not allow for recommendation of magnetic resonance angiography as part of the routine protocol. Finally, time repetition (TR) and time echo (TE) values used to evaluate patients with acute spinal cord injury vary significantly. All publications with MRI should specify the TR and TE values used. PMID:20388006

  12. Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using ...

  13. Thyroid hormones regulate skeletal muscle regeneration after acute injury.

    PubMed

    Leal, Anna Lúcia R C; Albuquerque, João Paulo C; Matos, Marina S; Fortunato, Rodrigo S; Carvalho, Denise P; Rosenthal, Doris; da Costa, Vânia Maria Corrêa

    2015-02-01

    We evaluated the effects of hypo- and hyperthyroid statuses during the initial phase of skeletal muscle regeneration in rats. To induce hypo- or hyperthyroidism, adult male Wistar rats were treated with methimazole (0.03%) or T4 (10 μg/100 g), respectively, for 10 days. Three days before sacrifice, a crush injury was produced in the solear muscles of one half of the animals, while the other half remained intact. T3, T4, TSH, and leptin serum levels were not affected by the injury. Serum T3 and T4 levels were significantly increased in hyperthyroid and hyper-injury animals. Hypothyroidism was confirmed by the significant increase in serum TSH levels in hypothyroid and hypo-injury animals. Injury increased cell infiltration and macrophage accumulation especially in hyperthyroid animals. Both type 2 and type 3 deiodinases were induced by lesion, and the opposite occurred with the type 1 isoform, at least in the control and hyperthyroid groups. Injury increased both MyoD and myogenin expression in all the studied groups, but only MyoD expression was increased by thyroidal status only at the protein level. We conclude that thyroid hormones modulate skeletal muscle regeneration possibly by regulating the inflammatory process, as well as MyoD and myogenin expression in the injured tissue. PMID:24798447

  14. The Role of Eugenol in the Prevention of Acute Pancreatitis-Induced Acute Kidney Injury: Experimental Study

    PubMed Central

    Markakis, Charalampos; Tsaroucha, Alexandra; Papalois, Apostolos E.; Lambropoulou, Maria; Spartalis, Eleftherios; Tsigalou, Christina; Romanidis, Konstantinos; Simopoulos, Constantinos

    2016-01-01

    Aim. Acute pancreatitis is an inflammatory intra-abdominal disease, which takes a severe form in 15–20% of patients and can result in high mortality especially when complicated by acute renal failure. The aim of this study is to assess the possible reduction in the extent of acute kidney injury after administration of eugenol in an experimental model of acute pancreatitis. Materials and Methods. 106 male Wistar rats weighing 220–350 g were divided into 3 groups: (1) Sham, with sham surgery; (2) Control, with induction of acute pancreatitis, through ligation of the biliopancreatic duct; and (3) Eugenol, with induction of acute pancreatitis and eugenol administration at a dose of 15 mg/kg. Serum urea and creatinine, histopathological changes, TNF-α, IL-6, and MPO activity in the kidneys were evaluated at predetermined time intervals. Results. The group that was administered eugenol showed milder histopathological changes than the Control group, TNF-α activity was milder in the Eugenol group, and there was no difference in activity for MPO and IL-6. Serum urea and creatinine levels were lower in the Eugenol group than in the Control group. Conclusions. Eugenol administration was protective for the kidneys in an experimental model of acute pancreatitis in rats. PMID:26884642

  15. 17β-estradiol protects the lung against acute injury: possible mediation by vasoactive intestinal polypeptide.

    PubMed

    Hamidi, Sayyed A; Dickman, Kathleen G; Berisha, Hasan; Said, Sami I

    2011-12-01

    Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ERα and ERβ and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60-90 min. Lung injury was marked by significant increases in the above measurements, with paraquat producing the most severe, and excitotoxicity the least severe, injury. Estradiol significantly attenuated the injury in each model. Both ER were constitutively expressed and immunohistochemically demonstrable in normal lung, and their selective agonists reduced anoxic injury, the only model in which they were tested. As it protected against injury, estradiol rapidly and significantly stimulated VIP mRNA expression in rat lung. Estradiol attenuated acute lung injury in three experimental models while stimulating VIP gene expression, a known mechanism of lung protection. The up-regulated VIP expression could have partially mediated the protection by estrogen. PMID:22009726

  16. 17β-Estradiol Protects the Lung against Acute Injury: Possible Mediation by Vasoactive Intestinal Polypeptide

    PubMed Central

    Hamidi, Sayyed A.; Dickman, Kathleen G.; Berisha, Hasan

    2011-01-01

    Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ERα and ERβ and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60–90 min. Lung injury was marked by significant increases in the above measurements, with paraquat producing the most severe, and excitotoxicity the least severe, injury. Estradiol significantly attenuated the injury in each model. Both ER were constitutively expressed and immunohistochemically demonstrable in normal lung, and their selective agonists reduced anoxic injury, the only model in which they were tested. As it protected against injury, estradiol rapidly and significantly stimulated VIP mRNA expression in rat lung. Estradiol attenuated acute lung injury in three experimental models while stimulating VIP gene expression, a known mechanism of lung protection. The up-regulated VIP expression could have partially mediated the protection by estrogen. PMID:22009726

  17. Diagnosis and treatment of acute ankle injuries: development of an evidence-based algorithm

    PubMed Central

    Polzer, Hans; Kanz, Karl Georg; Prall, Wolf Christian; Haasters, Florian; Ockert, Ben; Mutschler, Wolf; Grote, Stefan

    2011-01-01

    Acute ankle injuries are among the most common injuries in emergency departments. However, there are still no standardized examination procedures or evidence-based treatment. Therefore, the aim of this study was to systematically search the current literature, classify the evidence, and develop an algorithm for the diagnosis and treatment of acute ankle injuries. We systematically searched PubMed and the Cochrane Database for randomized controlled trials, meta-analyses, systematic reviews or, if applicable, observational studies and classified them according to their level of evidence. According to the currently available literature, the following recommendations have been formulated: i) the Ottawa Ankle/Foot Rule should be applied in order to rule out fractures; ii) physical examination is sufficient for diagnosing injuries to the lateral ligament complex; iii) classification into stable and unstable injuries is applicable and of clinical importance; iv) the squeeze-, crossed leg- and external rotation test are indicative for injuries of the syndesmosis; v) magnetic resonance imaging is recommended to verify injuries of the syndesmosis; vi) stable ankle sprains have a good prognosis while for unstable ankle sprains, conservative treatment is at least as effective as operative treatment without the related possible complications; vii) early functional treatment leads to the fastest recovery and the least rate of reinjury; viii) supervised rehabilitation reduces residual symptoms and re-injuries. Taken these recommendations into account, we present an applicable and evidence-based, step by step, decision pathway for the diagnosis and treatment of acute ankle injuries, which can be implemented in any emergency department or doctor's practice. It provides quality assurance for the patient and promotes confidence in the attending physician. PMID:22577506

  18. Haemodynamic collapse in a patient with acute inferior myocardial infarction and concomitant traumatic acute spinal cord injury.

    PubMed

    Kumagai, Naoto; Dohi, Kaoru; Tanigawa, Takashi; Ito, Masaaki

    2013-01-01

    A 71-year-old man suddenly collapsed and went into cardiopulmonary arrest. The cardiopulmonary resuscitation attempt succeeded in restoration of spontaneous circulation. The initial 12-lead electrocardiogram showed inferior acute myocardial infarction (AMI). The patient was initially diagnosed as having cardiogenic shock associated with inferior AMI. In spite of early coronary revascularisation, bradycardia and hypotension were sustained. After termination of sedation and extubation, he was found to have a quadriplegia and diagnosed with a cervical spinal cord injury (SCI). Therefore, the patient was finally diagnosed with neurogenic shock caused by acute cervical SCI due to the traumatic injury preceded by loss of consciousness complicating inferior AMI. We should recognise that SCI has unique haemodynamic features that mimic those associated with inferior AMI, but requires very different treatment. PMID:24272986

  19. Acute Reduction of Microglia Does Not Alter Axonal Injury in a Mouse Model of Repetitive Concussive Traumatic Brain Injury

    PubMed Central

    Bennett, Rachel E.

    2014-01-01

    Abstract The pathological processes that lead to long-term consequences of multiple concussions are unclear. Primary mechanical damage to axons during concussion is likely to contribute to dysfunction. Secondary damage has been hypothesized to be induced or exacerbated by inflammation. The main inflammatory cells in the brain are microglia, a type of macrophage. This research sought to determine the contribution of microglia to axon degeneration after repetitive closed-skull traumatic brain injury (rcTBI) using CD11b-TK (thymidine kinase) mice, a valganciclovir-inducible model of macrophage depletion. Low-dose (1 mg/mL) valganciclovir was found to reduce the microglial population in the corpus callosum and external capsule by 35% after rcTBI in CD11b-TK mice. At both acute (7 days) and subacute (21 days) time points after rcTBI, reduction of the microglial population did not alter the extent of axon injury as visualized by silver staining. Further reduction of the microglial population by 56%, using an intermediate dose (10 mg/mL), also did not alter the extent of silver staining, amyloid precursor protein accumulation, neurofilament labeling, or axon injury evident by electron microscopy at 7 days postinjury. Longer treatment of CD11b-TK mice with intermediate dose and treatment for 14 days with high-dose (50 mg/mL) valganciclovir were both found to be toxic in this injury model. Altogether, these data are most consistent with the idea that microglia do not contribute to acute axon degeneration after multiple concussive injuries. The possibility of longer-term effects on axon structure or function cannot be ruled out. Nonetheless, alternative strategies directly targeting injury to axons may be a more beneficial approach to concussion treatment than targeting secondary processes of microglial-driven inflammation. PMID:24797413

  20. Effects of acute selective pudendal nerve electrical stimulation after simulated childbirth injury

    PubMed Central

    Gill, Bradley C.; Dissaranan, Charuspong; Zutshi, Massarat; Balog, Brian M.; Lin, Danli; Damaser, Margot S.

    2013-01-01

    During childbirth, a combinatorial injury occurs and can result in stress urinary incontinence (SUI). Simulated childbirth injury, consisting of vaginal distension (VD) and pudendal nerve crush (PNC), results in slowed recovery of continence, as well as decreased expression of brain-derived neurotrophic factor (BDNF), a regenerative cytokine. Electrical stimulation has been shown to upregulate BDNF in motor neurons and facilitate axon regrowth through the increase of βII-tubulin expression after injury. In this study, female rats underwent selective pudendal nerve motor branch (PNMB) stimulation after simulated childbirth injury or sham injury to determine whether such stimulation affects bladder and anal function after injury and whether the stimulation increases BDNF expression in Onuf's nucleus after injury. Rats received 4 h of VD followed by bilateral PNC and 1 h of subthreshold electrical stimulation of the left PNMB and sham stimulation of the right PNMB. Rats underwent filling cystometry and anal pressure recording before, during, and after the stimulation. Bladder and anal contractile function were partially disrupted after injury. PNMB stimulation temporarily inhibited bladder contraction after injury. Two days and 1 wk after injury, BDNF expression in Onuf's nucleus of the stimulated side was significantly increased compared with the sham-stimulated side, whereas βII-tubulin expression in Onuf's nucleus of the stimulated side was significantly increased only 1 wk after injury. Acute electrical stimulation of the pudendal nerve proximal to the crush site upregulates BDNF and βII-tubulin in Onuf's nucleus after simulated childbirth injury, which could be a potential preventive option for SUI after childbirth injury. PMID:23152293

  1. Acute inflammatory response in spinal cord following impact injury.

    PubMed

    Carlson, S L; Parrish, M E; Springer, J E; Doty, K; Dossett, L

    1998-05-01

    Numerous factors are involved in the spread of secondary damage in spinal cord after traumatic injury, including ischemia, edema, increased excitatory amino acids, and oxidative damage to the tissue from reactive oxygen species. Neutrophils and macrophages can produce reactive oxygen species when activated and thus may contribute to the lipid peroxidation that is known to occur after spinal cord injury. This study examined the rostral-caudal distribution of neutrophils and macrophages/microglia at 4, 6, 24, and 48 h after contusion injury to the T10 spinal cord of rat (10 g weight, 50 mm drop). Neutrophils were located predominantly in necrotic regions, with a time course that peaked at 24 h as measured with assays of myeloperoxidase activity (MPO). The sharpest peak of MPO activity was localized between 4 mm rostral and caudal to the injury. Macrophages/microglia were visualized with antibodies against ED1 and OX-42. Numerous cells with a phagocytic morphology were present by 24 h, with a higher number by 48 h. These cells were predominantly located within the gray matter and dorsal funiculus white matter. The number of cells gradually declined through 6 mm rostral and caudal to the lesion. OX-42 staining also revealed reactive microglia with blunt processes, particularly at levels distant to the lesion. The number of macrophages/microglia was significantly correlated with the amount of tissue damage at each level. Treatments to decrease the inflammatory response are likely to be beneficial to recovery of function after traumatic spinal cord injury. PMID:9582256

  2. Work-Time Exposure and Acute Injuries in Inshore Lobstermen of the Northeast United States.

    PubMed

    Fulmer, Scott; Buchholz, Bryan; Jenkins, Paul; Scribani, Melissa

    2016-01-01

    The objective of this study was to inform efforts to reduce risk for musculoskeletal disorders among commercial lobstermen by characterizing and quantifying injuries that occur to people while harvesting lobsters commercially in the Northeast United States. This study aimed to estimate a denominator of exposure to lobstering in full-time equivalents (FTE), to estimate a fatality rate, and to calculate incidence rates for acute injuries within the sample population. Captains were randomly selected from those licensed to fish in Maine and Massachusetts. Data on work exposure and injuries with rapid onset that occurred on the boat ("acute injuries") were collected using a survey, which was administered quarterly via phone or face-to-face interview with the captain. The quarterly survey assessed the number of weeks worked during the quarter, average crew size, number of trips per week, and average trip length in hours. In addition, this survey captured relevant information (body segment affected, type of injury, and whether treatment was received) on all acute injuries occurring during the quarter. FTE were estimated using fishermen days and fishermen hours. The annual FTE estimated using days was 2,557 and using hours was 2,855. As expected, the summer months (3rd quarter) had the highest FTE and the winter (1st quarter) the lowest FTE. Fall (4th quarter) and spring (2nd quarter) ranked second and third, respectively. The incidence rates for all injuries (49.7/100 FTE) and injuries requiring treatment (15.0/100 FTE) were much higher than those reported in other studies of fishing that used Coast Guard data. PMID:26788780

  3. Acute kidney injury: highlights from the ERA-EDTA Congress in London.

    PubMed

    Sever, Mehmet Sukru

    2016-02-01

    The ERA-EDTA 52nd Congress was held in London, 28-31 May 2015. In the scientific programme, overall, during the symposium, there were 18 lectures, 3 minilectures, 15 free communications and 135 poster presentations on acute kidney injury (AKI). Among many excellent reports and presentations, I selected three hot topics on AKI for the readership of Nephrology Dialysis Transplantation. PMID:26769681

  4. Bioinforrnatics of Gene Expression Profiling Data Provide Mechanistic Understanding of Acute Ozone-Induced Lung injury

    EPA Science Inventory

    Acute ozone-induced pulmonary injury and inflammation are well characterized. A few studies have used gene expression profiling to determine the types of changes induced by ozone; however the mechanisms or the pathways involved are less well understood. We presumed that robust bi...

  5. The use of spinal manipulation to treat an acute on field athletic injury: a case report

    PubMed Central

    Duquette, Sean A.; Kazemi, Mohsen

    2016-01-01

    This case describes the utilization of spinal manipulative therapy for an acute athletic injury during a Taekwondo competition. During the tournament, an athlete had a sudden, non-traumatic, ballistic movement of the cervical spine. This resulted in the patient having a locked cervical spine with limited active motion in all directions. The attending chiropractor assessed the athlete, and deemed manipulation was appropriate. After the manipulation, the athlete’s range of motion was returned and was able to finish the match. Spinal manipulation has multiple positive outcomes for an athlete with an acute injury including the increase of range of motion, decrease in pain and the relaxation of hypertonic muscles. However, there should be some caution when utilizing manipulation during an event. In the article the authors propose four criteria that should be met before utilizing manipulation for an acute, in competition, athletic injury. These include the lack of red flags, limited time for the intervention, preexisting doctor-patient relationship and the athlete has experience receiving spinal manipulation. Clinicians should be aware that manipulation may be an effective tool to treat an acute in competition athletic injury. The criteria set out in the article may help a practitioner decide if manipulation is a good option for them. PMID:27385835

  6. Timed and targeted therapy for acute kidney injury: a glimpse of the future.

    PubMed

    Mehta, Ravindra L

    2010-06-01

    Whether and when to intervene and with which therapeutic agent are key questions physicians face daily in managing patients. Biomarkers are emerging to define the course of acute kidney injury and offer an opportunity to provide targeted interventions. The EARLYARF study by Endre et al. provides a glimpse of the challenges and opportunities that lie ahead. PMID:20467432

  7. Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B

    PubMed Central

    Shin, So Youn; Jeong, Sook-Hyang; Sung, Pil Soo; Lee, Jino; Kim, Hyung Joon; Lee, Hyun Woong

    2016-01-01

    Purpose Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. Materials and Methods Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. Results Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. Conclusion We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis. PMID:26996565

  8. Finding the cause of acute kidney injury: which index of fractional excretion is better?

    PubMed

    Gotfried, Jonathan; Wiesen, Jonathan; Raina, Rupesh; Nally, Joseph V

    2012-02-01

    The fractional excretion of urea (FEU) is a useful index for differentiating the main categories of causes of acute kidney injury, ie, prerenal causes and intrinsic causes. It may be used in preference to the more widely used fractional excretion of sodium (FENa) in situations in which the validity of the latter is limited, such as in patients taking a diuretic. PMID:22301562

  9. MATRILYSIN PARTICIPATES IN THE ACUTE LUNG INJURY INDUCED BY OIL COMBUSTION PRODUCTS

    EPA Science Inventory

    ROLE OF MATRILYSIN IN THE ACUTE LUNG INJURY INDUCED BY OIL COMBUSTION PARTICLES.

    K L Dreher1, WY Su2 and C L Wilson3. 1US Environmental Protection Agency, Research Triangle Park, NC; 2Duke University, Durham, NC;3Washington University, St. Louis, MO.

    Mechanisms by ...

  10. The use of spinal manipulation to treat an acute on field athletic injury: a case report.

    PubMed

    Duquette, Sean A; Kazemi, Mohsen

    2016-06-01

    This case describes the utilization of spinal manipulative therapy for an acute athletic injury during a Taekwondo competition. During the tournament, an athlete had a sudden, non-traumatic, ballistic movement of the cervical spine. This resulted in the patient having a locked cervical spine with limited active motion in all directions. The attending chiropractor assessed the athlete, and deemed manipulation was appropriate. After the manipulation, the athlete's range of motion was returned and was able to finish the match. Spinal manipulation has multiple positive outcomes for an athlete with an acute injury including the increase of range of motion, decrease in pain and the relaxation of hypertonic muscles. However, there should be some caution when utilizing manipulation during an event. In the article the authors propose four criteria that should be met before utilizing manipulation for an acute, in competition, athletic injury. These include the lack of red flags, limited time for the intervention, preexisting doctor-patient relationship and the athlete has experience receiving spinal manipulation. Clinicians should be aware that manipulation may be an effective tool to treat an acute in competition athletic injury. The criteria set out in the article may help a practitioner decide if manipulation is a good option for them. PMID:27385835

  11. Treatment of mild to moderate pain of acute soft tissue injury: diflunisal vs acetaminophen with codeine.

    PubMed

    Muncie, H L; King, D E; DeForge, B

    1986-08-01

    Acute soft tissue injuries create pain and limitation of function. Treatment requires analgesia and time for full recovery. Acetaminophen with codeine (650 mg plus 60 mg, respectively, every 4 to 6 hours) is used frequently as the analgesic of choice. Diflunisal (1,000 mg initially then 500 mg twice a day) vs acetaminophen with codeine was prospectively studied in the treatment of acute mild to moderate pain from soft tissue injuries. Thirty-five patients with acute strains, sprains, or low back pain were randomized to treatment (17 acetaminophen with codeine vs 18 diflunisal). Both groups were similar in the amount of pain and type of injury at initiation of therapy. Patient pain rating went from 3.3 +/- 0.6 to 1.6 +/- 1.5 for acetaminophen with codeine and from 3.3 +/- 0.6 to 1.3 +/- 1.1 for diflunisal. However, 65 percent of acetaminophen with codeine patients experienced side effects, with 35 percent of these patients stopping the medication because of intolerable side effects. In the diflunisal group, 28 percent of the patients experienced side effects and 5 percent had to stop the medication early. Diflunisal was found to be an effective analgesic in mild to moderate pain of acute soft tissue injuries, and caused fewer and more tolerable side effects than did acetaminophen with codeine. PMID:2942630

  12. CARDIOVASCULAR INJURY FROM ACUTE AND REPEATED EXPOSURE TO PARTICULATE MATTER (PM): POTENTIAL ROLE OF ZINC

    EPA Science Inventory

    CARDIOVASCULAR INJURY FROM ACUTE AND REPEATED EXPOSURE TO PARTICULATE MATTER (PM): POTENTIAL ROLE OF ZINC. UP Kodavanti, MC Schladweiler, AD Ledbetter, RH Jaskot, PS Gilmour, DC Christiani, WP Watkinson, DL Costa, JK McGee, A Nyska. NHEERL, USEPA, RTP, NC; CEMALB, UNC, Chapel Hil...

  13. ROLE OF CELL SIGNALING IN PROTECTION FROM DIESEL AND LPS INDUCED ACUTE LUNG INJURY

    EPA Science Inventory

    We have previously demonstrated in CD-1 mice that pre-administration of N-acetyl cysteine (NAC) or the p38 MAP kinase inhibitor (SB203580) reduces acute lung injury and inflammation following pulmonary exposures to diesel exhaust particles (DEP) or lipopolysaccharide (LPS). Here ...

  14. Acute effects of all-trans-retinoic acid in ischemic injury

    Technology Transfer Automated Retrieval System (TEKTRAN)

    All-trans-retinoic acid (ATRA) is a vitamin A derivative that is important in neuronal patterning, survival, and neurite outgrowth. We investigated the relatively acute effects of ATRA (100 nM and 1 µM) on cell swelling in ischemic injury and on key features hypothesized to contribute to cell swelli...

  15. Association between ambient noise exposure, hearing acuity, and risk of acute occupational injury

    PubMed Central

    Cantley, Linda F; Galusha, Deron; Cullen, Mark R; Dixon-Ernst, Christine; Rabinowitz, Peter M; Neitzel, Richard L

    2015-01-01

    Objective This study aimed to examine the associations between acute workplace injury risk, ambient noise exposure, and hearing acuity, adjusting for reported hearing protection use. Methods In a cohort of 9220 aluminum manufacturing workers studied over six years (33 300 person-years, 13 323 person-jobs), multivariate mixed effects models were used to estimate relative risk (RR) of all injuries as well as serious injuries by noise exposure category and hearing threshold level (HTL) adjusting for recognized and potential confounders. Results Compared to noise <82 dBA, higher exposure was associated with elevated risk in a monotonic and statistically significant exposure–response pattern for all injuries and serious injuries with higher risk estimates observed for serious injuries [82–84.99 dBA: RR 1.26, 95% confidence interval (95% CI) 0.96–1.64; 85–87.99 dBA: RR 1.39, 95% CI 1.05–1.85; ≥88 dBA: RR 2.29, 95% CI 1.52–3.47]. Hearing loss was associated with increased risk for all injuries, but was not a significant predictor of risk for the subset of more serious injuries. Compared to those without hearing loss, workers with HTL ≥25 dB had 21% increased all injury risk (RR 1.21, 95% CI 1.09–1.33) while those with HTL 10–24.99 dB had 6% increased risk (RR 1.06, 95% CI 1.00–1.13). Reported hearing protection type did not predict injury risk. Conclusion Noise exposure levels as low as 85 dBA may increase workplace injury risk. HTL was associated with increased risk for all, but not the subset of serious, injuries. Additional study is needed both to confirm the observed associations and explore causal pathways. PMID:25137556

  16. Molecular Ultrasound Imaging of Tissue Inflammation Using an Animal Model of Acute Kidney Injury

    PubMed Central

    Hoyt, Kenneth; Warram, Jason M.; Wang, Dezhi; Ratnayaka, Sithira; Traylor, Amie; Agarwal, Anupam

    2016-01-01

    Purpose The objective of this study was to evaluate the use of molecular ultrasound (US) imaging for monitoring the early inflammatory effects following acute kidney injury. Procedures A population of rats underwent 30 min of renal ischemia (acute kidney injury, N=6) or sham injury (N=4) using established surgical methods. Animals were divided and molecular US imaging was performed during the bolus injection of a targeted microbubble (MB) contrast agent to either P-selectin or vascular cell adhesion molecule 1 (VCAM-1). Imaging was performed before surgery and 4 and 24 h thereafter. After manual segmentation of renal tissue space, the molecular US signal was calculated as the difference between time-intensity curve data before MB injection and after reaching steady-state US image enhancement. All animals were terminated after the 24 h imaging time point and kidneys excised for immunohistochemical (IHC) analysis. Results Renal inflammation was analyzed using molecular US imaging. While results using the P-selectin and VCAM-1 targeted MBs were comparable, it appears that the former was more sensitive to biomarker expression. All molecular US imaging measures had a positive correlation with IHC findings. Conclusions Acute kidney injury is a serious disease in need of improved noninvasive methods to help diagnose the extent of injury and monitor the tissue throughout disease progression. Molecular US imaging appears well suited to address this challenge and more research is warranted. PMID:25905474

  17. Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage

    PubMed Central

    Johnsen, Marc; Späth, Martin Richard; Denzel, Martin S.; Göbel, Heike; Kubacki, Torsten; Hoyer, Karla Johanna Ruth; Hinze, Yvonne; Benzing, Thomas; Schermer, Bernhard; Antebi, Adam; Burst, Volker; Müller, Roman-Ulrich

    2016-01-01

    Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID:27557097

  18. Retroperitoneal abscess and acute acalculous cholecystitis after iatrogenic colon injury: report of a case

    PubMed Central

    Dong, Chengwei; Wang, Yuxu; Hu, Sanyuan; Du, Futian; Ding, Wei

    2015-01-01

    Acute acalculous cholecystitis has a high mortality rate due to the difficulties in early diagnosis and high rate of complications like empyema, gangrene and perforation. We report a case of 20-year-old male with acute severe pancreatitis, acute renal failure and acute peripancreatic fluid collection who was transferred to our department after blood filtration treatment in ICU. After percutaneous catheter drainage for 20 hours, the patient got a high fever. Computed tomography revealed retroperitoneal colon injury. In this case, percutaneous catheter drainage was performed again and the pus cavity was flushed regularly, after which the patient’s state gradually improved. Unpredictably, septic shock appeared on the 51st day. Repeated computed tomography revealed acute acalculous cholecystitis and abscess formation. After percutaneous transhepatic gallbladder catheterization and drainage, the patient got better gradually. Three months later the retroperitoneal catheter was removed. Four months later, ultrasound examination showed normal gallbladder and the catheter was removed. PMID:26131252

  19. Biopsy-proven drug-induced tubulointerstitial nephritis in a patient with acute kidney injury and alcoholic severe acute pancreatitis.

    PubMed

    Yoshioka, Wakako; Mori, Takayasu; Nagahama, Kiyotaka; Tamura, Teiichi

    2013-01-01

    We report a 49-year-old man with alcoholic severe acute pancreatitis (SAP) complicated by drug-induced acute tubulointerstitial nephritis (DI-AIN). Oliguria persisted and became anuric again on day 17 despite improvement of pancreatitis. He presented rash, fever and eosinophilia from day 20. Renal biopsy was performed for dialysis-dependent acute kidney injury (AKI), DI-AIN was revealed, and prompt use of corticosteroids fully restored his renal function. This diagnosis might be missed because it is difficult to perform renal biopsy in such a clinical situation. If the patient's general condition allows, renal biopsy should be performed and reversible AKI must be distinguished from many cases of irreversible AKI complicated by SAP. This is the first report of biopsy-proven DI-AIN associated with SAP, suggesting the importance of biopsy for distinguishing DI-AIN in persisting AKI of SAP. PMID:23645698

  20. Clinical course of acute chemical lung injury caused by 3-chloropentafluoropene.

    PubMed

    Morita, Satomu; Takimoto, Takayuki; Kawahara, Kunimitsu; Nishi, Katsuji; lino, Morio

    2013-01-01

    Perfluoroallyl chloride (PFAC), a fluorine-containing compound, has very severe toxicity, but this toxicity is not well characterised. We report a fatal case of acute chemical lung injury caused by the inhalation of PFAC. A 39-year-old man, working at a chemical factory, inhaled PFAC gas and died 16 days later of acute lung injury with severe pneumothorax. We present his clinical course together with thoracic CT findings, autopsy and analysis of PFAC in blood and urine samples with gas chromatograph-mass spectrometry. Previously, a fatal case of PFAC was reported in 1981 but PFAC was not identified in any of the patient's samples. In our patient, we identified PFAC in both blood and urine samples. Our toxicological analysis may be used as a reference to detect PFAC toxicity in the future. Our study should be helpful for diagnosing lung injury induced by a highly toxic gas, such as PFAC. PMID:24311414

  1. Ibuprofen in the treatment of acute ankle joint injuries. A double-blind study.

    PubMed

    Fredberg, U; Hansen, P A; Skinhøj, A

    1989-01-01

    Sixty-eight patients who presented to the casualty ward with acute ankle joint injuries were studied to examine the effect of ibuprofen on pain and ankle swelling. Thirty-two patients were treated with placebo tablets and 36 with 600 mg ibuprofen tablets taken four times a day for 4 to 6 days. All of the patients were immobilized and requested to keep the foot elevated. The results showed that ibuprofen had no effect on the ankle swelling. The need for additional analgesics was not influenced by treatment with ibuprofen, which means that ibuprofen has no effect on pain. The time elapsed from occurrence of the injury to arrival at the casualty ward was negatively correlated to the reduction of ankle joint swelling during the treatment period. Treatment with ice-sprays, icebags, or cold water during the acute stage of injury did not influence the reduction of swelling during the treatment period. PMID:2675651

  2. Postoperative management and acute rehabilitation of patients with spinal cord injuries.

    PubMed

    McCagg, C

    1986-01-01

    The mortality and morbidity rates of patients with spinal cord injury have decreased greatly. Prior to World War II, few patients survived their acute injuries. Now even severely involved respiratory-dependent patients may return to live in the community. Advanced surgical procedures, when appropriately applied, are decreasing the time of immobility and preventing late spinal deformities. Exciting new developments in basic science research such as the use of thyrotropin-releasing hormone and functional electrical stimulation may alter the whole course of recovery for patients within the foreseeable future. It is likely, however, that the acute management of the patient with spinal cord injury will still demand systematic care by an experienced, multidisciplinary team of professionals. PMID:3945478

  3. Renin-angiotensin system and its role in hyperoxic acute lung injury.

    PubMed

    Zhang, P X; Han, C H; Zhou, F J; Li, L; Zhang, H M; Liu, W W

    2016-01-01

    Oxygen is essential to sustain life, but at a high partial pressure oxygen may cause toxicity to the human body. These injuries to the lung are known as hyperoxic acute lung injury [HALI]). To date, numerous studies have been conducted to investigate the pathogenesis of HALI, for which some hypotheses have been proposed. Accumulating evidence indicates that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of some lung diseases, including acute lung injury (ALI), chronic obstructive pulmonary disease (COPD) and HALI. In this review, we briefly introduce the classic RAS, local (tissue) RAS and intracellular RAS, and we summarize findings on the relationship between local/classic RAS and HALI. The importance--and ambiguity--of the results of these studies indicate a need for further investigations of the RAS and its role in the patho- genesis of HALI. PMID:27416692

  4. Clinical course of acute chemical lung injury caused by 3-chloropentafluoropene

    PubMed Central

    Morita, Satomu; Takimoto, Takayuki; Kawahara, Kunimitsu; Nishi, Katsuji

    2013-01-01

    Perfluoroallyl chloride (PFAC), a fluorine-containing compound, has very severe toxicity, but this toxicity is not well characterised. We report a fatal case of acute chemical lung injury caused by the inhalation of PFAC. A 39-year-old man, working at a chemical factory, inhaled PFAC gas and died 16 days later of acute lung injury with severe pneumothorax. We present his clinical course together with thoracic CT findings, autopsy and analysis of PFAC in blood and urine samples with gas chromatograph–mass spectrometry. Previously, a fatal case of PFAC was reported in 1981 but PFAC was not identified in any of the patient's samples. In our patient, we identified PFAC in both blood and urine samples. Our toxicological analysis may be used as a reference to detect PFAC toxicity in the future. Our study should be helpful for diagnosing lung injury induced by a highly toxic gas, such as PFAC. PMID:24311414

  5. Septic versus non-septic acute kidney injury in critically ill patients: characteristics and clinical outcomes

    PubMed Central

    Cruz, Marília Galvão; Dantas, João Gabriel Athayde de Oliveira; Levi, Talita Machado; Rocha, Mário de Seixas; de Souza, Sérgio Pinto; Boa-Sorte, Ney; de Moura, Carlos Geraldo Guerreiro; Cruz, Constança Margarida Sampaio

    2014-01-01

    Objective This study aimed to describe and compare the characteristics and clinical outcomes of patients with septic and non-septic acute kidney injury. Methods This study evaluated an open cohort of 117 critically ill patients with acute kidney injury who were consecutively admitted to an intensive care unit, excluding patients with a history of advanced-stage chronic kidney disease, kidney transplantation, hospitalization or death in a period shorter than 24 hours. The presence of sepsis and in-hospital death were the exposure and primary variables in this study, respectively. A confounding analysis was performed using logistic regression. Results No significant differences were found between the mean ages of the groups with septic and non-septic acute kidney injury [65.30±21.27 years versus 66.35±12.82 years, respectively; p=0.75]. In the septic and non-septic acute kidney injury groups, a predominance of females (57.4% versus 52.4%, respectively; p=0.49) and Afro-descendants (81.5% versus 76.2%, respectively; p=0.49) was observed. Compared with the non-septic patients, the patients with sepsis had a higher mean Acute Physiology and Chronic Health Evaluation II score [21.73±7.26 versus 15.75±5.98; p<0.001)] and a higher mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart failure (p<0.001) were more common in the non-septic patients. Septic acute kidney injury was associated with a greater number of patients who required dialysis (p=0.001) and a greater number of deaths (p<0.001); however, renal function recovery was more common in this group (p=0.01). Sepsis (OR: 3.88; 95%CI: 1.51-10.00) and an Acute Physiology and Chronic Health Evaluation II score >18.5 (OR: 9.77; 95%CI: 3.73-25.58) were associated with death in the multivariate analysis. Conclusion Sepsis was an independent predictor of death. Significant differences were found between the characteristics and clinical outcomes of patients with septic versus non-septic acute kidney

  6. Incidence and Risk Factors for Acute Kidney Injury Following Mannitol Infusion in Patients With Acute Stroke: A Retrospective Cohort Study.

    PubMed

    Lin, Shin-Yi; Tang, Sung-Chun; Tsai, Li-Kai; Yeh, Shin-Joe; Shen, Li-Jiuan; Wu, Fe-Lin Lin; Jeng, Jiann-Shing

    2015-11-01

    Mannitol, an osmotic diuretic, is commonly used to treat patients with acute brain edema, but its use also increases the risk of developing acute kidney injury (AKI). In this study, we investigated the incidence and risk factors of mannitol-related AKI in acute stroke patients.A total of 432 patients (ischemic stroke 62.3%) >20 years of age who were admitted to the neurocritical care center in a tertiary hospital and received mannitol treatment were enrolled in this study. Clinical parameters including the scores of National Institutes of Health Stroke Scale (NIHSS) at admission, vascular risk factors, laboratory data, and concurrent nephrotoxic medications were registered. Acute kidney injury was defined as an absolute elevation in the serum creatinine (Scr) level of ≥0.3 mg/dL from the baseline or a ≥50% increase in Scr.The incidence of mannitol-related AKI was 6.5% (95% confidence interval, 4.5%-9.3%) in acute stroke patients, 6.3% in patients with ischemic stroke, and 6.7% in patients with intracerebral hemorrhage. Multivariate analysis revealed that diabetes, lower estimated glomerular filtration rate at baseline, higher initial NIHSS score, and concurrent use of diuretics increased the risk of mannitol-related AKI. When present, the combination of these elements displayed an area under the receiver operating characteristic curve of 0.839 (95% confidence interval, 0.770-0.909). In conclusion, mannitol-related AKI is not uncommon in the treatment of acute stroke patients, especially in those with vulnerable risk factors. PMID:26632702

  7. Dialysis-requiring acute kidney injury among hospitalized adults with documented hepatitis C Virus infection: a nationwide inpatient sample analysis.

    PubMed

    Nadkarni, G N; Patel, A; Simoes, P K; Yacoub, R; Annapureddy, N; Kamat, S; Konstantinidis, I; Perumalswami, P; Branch, A; Coca, S G; Wyatt, C M

    2016-01-01

    Chronic hepatitis C virus (HCV) infection may cause kidney injury, particularly in the setting of cryoglobulinemia or cirrhosis; however, few studies have evaluated the epidemiology of acute kidney injury in patients with HCV. We aimed to describe national temporal trends of incidence and impact of severe acute kidney injury (AKI) requiring renal replacement 'dialysis-requiring AKI' in hospitalized adults with HCV. We extracted our study cohort from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project using data from 2004 to 2012. We defined HCV and dialysis-requiring acute kidney injury based on previously validated ICD-9-CM codes. We analysed temporal changes in the proportion of hospitalizations complicated by dialysis-requiring AKI and utilized survey multivariable logistic regression models to estimate its impact on in-hospital mortality. We identified a total of 4,603,718 adult hospitalizations with an associated diagnosis of HCV from 2004 to 2012, of which 51,434 (1.12%) were complicated by dialysis-requiring acute kidney injury. The proportion of hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly from 0.86% in 2004 to 1.28% in 2012. In-hospital mortality was significantly higher in hospitalizations complicated by dialysis-requiring acute kidney injury vs those without (27.38% vs 2.95%; adjusted odds ratio: 2.09; 95% confidence interval: 1.74-2.51). The proportion of HCV hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly between 2004 and 2012. Similar to observations in the general population, dialysis-requiring acute kidney injury was associated with a twofold increase in odds of in-hospital mortality in adults with HCV. These results highlight the burden of acute kidney injury in hospitalized adults with HCV infection. PMID:26189719

  8. Acute plastic bowing of the radius with a distal radioulnar joint injury: a case report.

    PubMed

    Uehara, Masashi; Yamazaki, Hiroshi; Kato, Hiroyuki

    2010-01-01

    Acute plastic bowing is an incomplete fracture with a deformation that shows no obvious macroscopic fracture line or cortical discontinuity. Although cases of acute plastic bowing of the ulna with a dislocation of the radial head have been previously reported, we present here a rare case of acute plastic bowing of the radius with a distal radioulnar joint injury in a 16-year-old boy. Internal fixation of the detached fragment to the ulnar styloid and repair of the triangular fibrocartilagenous complex resulted in the disappearance of wrist pain. In cases of distal radioulnar joint injuries in children or adolescents, radiographs of the entire forearm should be taken to evaluate the existence of radial bowing. PMID:21089197

  9. Strength Measurements in Acute Hamstring Injuries: Intertester Reliability and Prognostic Value of Handheld Dynamometry.

    PubMed

    Reurink, Gustaaf; Goudswaard, Gert Jan; Moen, Maarten H; Tol, Johannes L; Verhaar, Jan A N; Weir, Adam

    2016-08-01

    Study Design Cohort study, repeated measures. Background Although hamstring strength measurements are used for assessing prognosis and monitoring recovery after hamstring injury, their actual clinical relevance has not been established. Handheld dynamometry (HHD) is a commonly used method of measuring muscle strength. The reliability of HHD has not been determined in athletes with acute hamstring injuries. Objectives To determine the intertester reliability and the prognostic value of hamstring HHD strength measurement in acute hamstring injuries. Methods We measured knee flexion strength with HHD in 75 athletes at 2 visits, at baseline (within 5 days of hamstring injury) and follow-up (5 to 7 days after the baseline measurement). We assessed isometric hamstring strength in 15° and 90° of knee flexion. Reliability analysis testing was performed by 2 testers independently at the follow-up visit. We recorded the time needed to return to play (RTP) up to 6 months following baseline. Results The intraclass correlation coefficients of the strength measurements in injured hamstrings were between 0.75 and 0.83. There was a statistically significant but weak correlation between the time to RTP and the strength deficit at 15° of knee flexion measured at baseline (Spearman r = 0.25, P = .045) and at the follow-up visit (Spearman r = 0.26, P = .034). Up to 7% of the variance in time to RTP is explained by this strength deficit. None of the other strength variables were significantly correlated with time to RTP. Conclusion Hamstring strength can be reliably measured with HHD in athletes with acute hamstring injuries. The prognostic value of strength measurements is limited, as there is only a weak association between the time to RTP and hamstring strength deficit after acute injury. Level of Evidence Prognosis, level 4. J Orthop Sports Phys Ther 2016;46(8):689-696. Epub 12 May 2016. doi:10.2519/jospt.2016.6363. PMID:27170527

  10. Uncoupling of the autonomic and cardiovascular systems in acute brain injury.

    PubMed

    Goldstein, B; Toweill, D; Lai, S; Sonnenthal, K; Kimberly, B

    1998-10-01

    We hypothesized that acute brain injury results in decreased heart rate (HR) variability and baroreflex sensitivity indicative of uncoupling of the autonomic and cardiovascular systems and that the degree of uncoupling should be proportional to the degree of neurological injury. We used HR and blood pressure (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP and the transfer function magnitude (TF) between BP and HR as a measure of baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury (n = 7), multiple trauma (n = 6), head trauma (n = 5), central nervous system infection (n = 4), and intracranial hemorrhage (n = 2)], neurological injury and survival was associated with low-frequency (0.01-0.15 Hz) HR and BP power and TF. Brain-dead patients showed decreased low-frequency HR power [0. 51 +/- 0.36 (SE) vs. 2.54 +/- 0.14 beats/min2, P = 0.03] and TF [0. 61 +/- 0.16 (SE) vs. 1.29 +/- 0.07 beats . min-1 . mmHg-1, P = 0.05] compared with non-brain-dead patients. We conclude that 1) severity of neurological injury and outcome are inversely associated with HR and BP variability and 2) there is direct evidence for cardiovascular and autonomic uncoupling in acute brain injury with complete uncoupling during brain death. PMID:9756562

  11. Treatment of acute lung injury by targeting MG53-mediated cell membrane repair.

    PubMed

    Jia, Yanlin; Chen, Ken; Lin, Peihui; Lieber, Gissela; Nishi, Miyuki; Yan, Rosalie; Wang, Zhen; Yao, Yonggang; Li, Yu; Whitson, Bryan A; Duann, Pu; Li, Haichang; Zhou, Xinyu; Zhu, Hua; Takeshima, Hiroshi; Hunter, John C; McLeod, Robbie L; Weisleder, Noah; Zeng, Chunyu; Ma, Jianjie

    2014-01-01

    Injury to lung epithelial cells has a role in multiple lung diseases. We previously identified mitsugumin 53 (MG53) as a component of the cell membrane repair machinery in striated muscle cells. Here we show that MG53 also has a physiological role in the lung and may be used as a treatment in animal models of acute lung injury. Mice lacking MG53 show increased susceptibility to ischaemia-reperfusion and overventilation-induced injury to the lung when compared with wild-type mice. Extracellular application of recombinant human MG53 (rhMG53) protein protects cultured lung epithelial cells against anoxia/reoxygenation-induced injuries. Intravenous delivery or inhalation of rhMG53 reduces symptoms in rodent models of acute lung injury and emphysema. Repetitive administration of rhMG53 improves pulmonary structure associated with chronic lung injury in mice. Our data indicate a physiological function for MG53 in the lung and suggest that targeting membrane repair may be an effective means for treatment or prevention of lung diseases. PMID:25034454

  12. ROLE OF TACHYKININS IN OZONE-INDUCED ACUTE LUNG INJURY

    EPA Science Inventory

    To examine the hypothesis that the acute, reversible changes caused by O3 exposure are mediated by techykinin release, guinea pigs were depleted of tachykinins using repeated capsaicin (CAP) injections prior to O3 exposure, in an attempt to prevent O3-induced functional changes. ...

  13. Contribution of Mature Hepatocytes to Biliary Regeneration in Rats with Acute and Chronic Biliary Injury

    PubMed Central

    Chen, Ya-Hui; Chen, Hui-Ling; Chien, Chin-Sung; Wu, Shang-Hsin; Ho, Yi-Tian; Yu, Chun-Hsien; Chang, Mei-Hwei

    2015-01-01

    Whether hepatocytes can convert into biliary epithelial cells (BECs) during biliary injury is much debated. To test this concept, we traced the fate of genetically labeled [dipeptidyl peptidase IV (DPPIV)-positive] hepatocytes in hepatocyte transplantation model following acute hepato-biliary injury induced by 4,4’-methylene-dianiline (DAPM) and D-galactosamine (DAPM+D-gal) and in DPPIV-chimeric liver model subjected to acute (DAPM+D-gal) or chronic biliary injury caused by DAPM and bile duct ligation (DAPM+BDL). In both models before biliary injury, BECs are uniformly DPPIV-deficient and proliferation of DPPIV-deficient hepatocytes is restricted by retrorsine. We found that mature hepatocytes underwent a stepwise conversion into BECs after biliary injury. In the hepatocyte transplantation model, DPPIV-positive hepatocytes entrapped periportally proliferated, and formed two-layered plates along portal veins. Within the two-layered plates, the hepatocytes gradually lost their hepatocytic identity, proceeded through an intermediate state, acquired a biliary phenotype, and subsequently formed bile ducts along the hilum-to-periphery axis. In DPPIV-chimeric liver model, periportal hepatocytes expressing hepatocyte nuclear factor-1β (HNF-1β) were exclusively DPPIV-positive and were in continuity to DPPIV-positives bile ducts. Inhibition of hepatocyte proliferation by additional doses of retrorsine in DPPIV-chimeric livers prevented the appearance of DPPIV-positive BECs after biliary injury. Moreover, enriched DPPIV-positive BEC/hepatic oval cell transplantation produced DPPIV-positive BECs or bile ducts in unexpectedly low frequency and in mid-lobular regions. These results together suggest that mature hepatocytes but not contaminating BECs/hepatic oval cells are the sources of periportal DPPIV-positive BECs. We conclude that mature hepatocytes contribute to biliary regeneration in the environment of acute and chronic biliary injury through a ductal plate

  14. AN "INJURY-TIME INTEGRAL" MODEL FOR RELATING ACUTE TO CHRONIC INJURY TO PHOSGENE

    EPA Science Inventory


    ABSTRACT
    The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the "concentration x time" (C x T) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (m...

  15. The yin and yang of autophagy in acute kidney injury.

    PubMed

    Melk, Anette; Baisantry, Arpita; Schmitt, Roland

    2016-03-01

    Antagonizing the strongly activated pathway of autophagy in renal ischemic injury has been associated with poor outcome. In our recent study we used mice with a selective deletion of Atg5 in the S3 proximal tubule segment, which is most susceptible to ischemic damage. In line with the notion that autophagy is a prosurvival mechanism our studies revealed an early accelerated cell death of heavily damaged tubular cells in the S3 segment of these mice. Interestingly, this expedited loss of cells was associated with better long-term outcome as reflected by less inflammation, improved tubular repair, and function and reduced accumulation of senescent cells. While these data confirm the role of tubular autophagy as a prosurvival mechanism in ischemic kidney injury, they also show that autophagy may enable severely damaged cells to persist and exert deleterious effects. Such ambivalent effects might be of relevance if modulating autophagy is considered as a therapeutic option. PMID:26761120

  16. Nutritional treatment for acute and chronic traumatic brain injury patients.

    PubMed

    Curtis, L; Epstein, P

    2014-09-01

    Proper nutrition is critical for recovery from traumatic brain injury (TBI). Prompt enteral feeding of moderate to severe TBI patients has been associated with significantly lower mortality and rates of infection. Probiotic supplementation has been associated with significantly lower rates of infection in TBI and other trauma patients. Human studies have suggested that supplementation with omega 3 fats, vitamin D, N-Acetylcysteine, branched chain amino acids, and zinc may be helpful for recovery from TBI. Animal TBI models have suggested that alpha-lipoic acid, magnesium, taurine, coenzyme Q10, and many phytonutrients (such as resveratrol) are also helpful. Unfortunately, recent human clinical trials with citicoline in TBI and stroke patients have produced disappointing results. Much more research is needed on multifaceted nutritional strategies to treat TBI patients in both the immediate post-injury phase and throughout the patients lifespan. PMID:24844176

  17. Mechanisms of renal repair and survival following acute injury.

    PubMed

    Safirstein, R; DiMari, J; Megyesi, J; Price, P

    1998-09-01

    The reaction of the renal epithelium to injury is heterogenous. Some cells die, others survive apparently intact, while others commit to repair. The determinants of these responses appear to depend on signal transduction pathways and molecular responses that is segment specific and interactive. The kidney, as do cells in culture exposed to various noxious stimuli, react in a typical manner referred to as the stress response. The response is comprised of kinases and their molecular targets as well as cell cycle-specific factors that determine whether a cell survives the injury or not. We propose that this response can be modified by survival factors which upregulate those aspects of the response that are cytoprotective and which downregulate those that are cytoreductive. Preliminary data will be presented to demonstrate the feasibility of this approach. PMID:9754604

  18. Obstetric Acute Kidney Injury; A Three Year Experience at a Medical College Hospital in North Karnataka, India

    PubMed Central

    Lakshmi, K.S.; Gorikhan, Gousia; M.M., Umadi; S.T., Kalsad; M.P., Madhavaranga; Dambal, Amrut; Padaki, Samata

    2015-01-01

    Introduction: Acute kidney injury is a rare and sometimes fatal complication of pregnancy, the incidence of which has been declining worldwide, though still high in developing countries. There are recent observations of increasing incidence in some developed countries attributed to hypertensive disorders of pregnancy. Materials and Methods: In this study, we have analysed the records of all patients referred to the dialysis unit of a medical college hospital in Karnataka for acute kidney injury related to pregnancy. AKIN (Acute Kidney Injury Network) criteria for the diagnosis of acute kidney injury were adapted. Age, parity, gestational age, causative factors for acute kidney injury, mode of delivery, access to antenatal care, operative procedures, blood component transfusions, number of haemodialysis, time for initiation of haemodialysis, duration of hospital stay and mortality were analysed by finding mean, standard deviation and standard error. Results: Fifteen patients out of 21563 who delivered in our hospital developed acute kidney injury. These (n=15) were out of 149 patients of acute kidney injury of various aetiologies who underwent haemodialysis between 2012 and 2014. Of these two were unregistered for antenatal care. Ten were multiparous, Eleven were from rural background, one had home delivery, six had vaginal delivery, seven had caesarean section and two had second trimester abortion. Placental abruption with intrauterine death was the commonest Cause in 9 out of 15 cases. All had severe anaemia. Patients received a mean of 3.9 (SD+/- 2.4) sessions of haemodialysis. Eleven patients recovered completely, two died and two left against medical advice. Conclusion: Obstetric acute kidney injury is associated with poor access to antenatal care, multiparity and rural background. Placental abruption is the commonest cause of obstetric acute kidney injury. Blood component transfusions, avoidance of nephrotoxic drugs and early initiation of haemodialysis are

  19. Cholestatic jaundice, acute kidney injury and acute pancreatitis secondary to the recreational use of methandrostenolone: a case report

    PubMed Central

    2011-01-01

    Introduction Over the last few years the use of anabolic steroids has become increasingly common amongst amateur athletes and for aesthetic purposes. As a result, the adverse events related to their use are being seen more frequently. Methandrostenolone is an anabolic steroid which is widely available and has been used for both performance enhancement and aesthetic purposes. This drug has also been reported to cause cholestasis of the intra-hepatic bile ducts resulting in elevated aminotransferases, hyperbilirubinemia and clinical jaundice. However, to the best of our knowledge this agent has not been previously reported to cause pancreatitis or acute kidney injury. Case presentation In this paper, we report the case of a 50-year-old man of Indian descent who presented with a six week history of diffuse abdominal pain, anorexia and weight loss following an eight week cycle of methandrostenolone use. At initial presentation, his lipase level was 785 U/L, bilirubin was 922 μmol/L and creatinine was 200 U/L while his aspartate aminotransferase and alanine aminotransferase levels were only mildly elevated at 61 U/L and 56 U/L respectively. His lipase peaked on day nine at >3000 U/L whilst his creatinine level was 299 U/L. Imaging was consistent with acute pancreatitis while a liver biopsy was consistent with intra-hepatic cholestasis and a kidney biopsy revealed evidence of acute tubular necrosis. Conclusion Both acute pancreatitis and acute kidney injury have rarely been reported with anabolic steroid use and they have not been previously reported to occur in the same patient. This case demonstrates some potentially new and serious adverse consequences occurring with the use of anabolic steroids, of which physicians need to be aware. PMID:21470406

  20. Monocytic Tissue Transglutaminase in a Rat Model for Reversible Acute Rejection and Chronic Renal Allograft Injury

    PubMed Central

    Zakrzewicz, Anna; Atanasova, Srebrena; Padberg, Winfried

    2015-01-01

    Acute rejection is a major risk factor for chronic allograft injury (CAI). Blood leukocytes interacting with allograft endothelial cells during acute rejection were suggested to contribute to the still enigmatic pathogenesis of CAI. We hypothesize that tissue transglutaminase (Tgm2), a multifunctional protein and established marker of M2 macrophages, is involved in acute and chronic graft rejection. We focus on leukocytes accumulating in blood vessels of rat renal allografts (Fischer-344 to Lewis), an established model for reversible acute rejection and CAI. Monocytes in graft blood vessels overexpress Tgm2 when acute rejection peaks on day 9 after transplantation. Concomitantly, caspase-3 is activated, suggesting that Tgm2 expression is linked to apoptosis. After resolution of acute rejection on day 42, leukocytic Tgm2 levels are lower and activated caspase-3 does not differ among isografts and allografts. Cystamine was applied for 4 weeks after transplantation to inhibit extracellular transglutaminase activity, which did, however, not reduce CAI in the long run. In conclusion, this is the first report on Tgm2 expression by monocytes in vivo. Tgm2 may be involved in leukocytic apoptosis and thus in reversion of acute rejection. However, our data do not support a role of extracellular transglutaminase activity as a factor triggering CAI during self-limiting acute rejection. PMID:26063971

  1. VEGF and BFGF Expression and Histological Characteristics of the Bone-Tendon Junction during Acute Injury Healing

    PubMed Central

    Wang, Lin; Gao, Weiwei; Xiong, Kaiyu; Hu, Kuan; Liu, Xincun; He, Hui

    2014-01-01

    Bone-tendon junction (BTJ) injuries are common and may be caused by acute trauma and delayed healing during exercise or work. To understand the nature of the healing process of BTJ injuries would help to prevent injuries and improve treatment. Thirty-three mature female rabbit hindlimbs were assigned to normal control (CON, n = 7) and injury groups (n = 26). The acute injury was established by administering one 7 plum-blossom needle puncture. Specimens were harvested post injury at 1, 2, 4, and 8 weeks (ND1W, n = 6; ND2W, n = 6; ND4W, n = 7; and ND8W, n = 7). The injury existed in all of the injury groups. Compared with the CON group, all of the animals in the injury group showed poor cell profiles, an unclear or undetectable tide mark, a proteoglycan area and profile changes; the BTJ cell density diminished significantly in the ND1W (p < 0.01), ND2W (p < 0.05), ND4W (p < 0.01), and ND8W groups (p < 0.01); the fibrocartilage zone thickness in all injury groups was significantly thicker than in the CON group (p < 0.05), but no significant difference was found among the injury groups (p>0.05). The basic fibroblast growth factor (bFGF) expression in the CON group was significantly less than in the ND1W group (p<0.01), but no significant difference was found when compared with the ND2W, ND4W, and ND8W groups. The bFGF expression in the ND1W group was higher than that of the ND4W (p < 0.05) and ND8W groups (p < 0.01). The vascular endothelial growth factor (VEGF) levels were not significantly different among the groups (p > 0.05). The bFGF and VEGF expression levels indicated that the healing process stopped at 8 weeks post injury or was not activated, although the injury had not healed by histological examination. A repeatable animal model of BTJ acute injury was established in this study, and the results described the BTJ acute injury healing difficult concerned with the repairing stop. Key Points This study described the bone-tendon junction acute injury nature

  2. Endothelial-cell injury in cutaneous acute graft-versus-host disease.

    PubMed Central

    Dumler, J. S.; Beschorner, W. E.; Farmer, E. R.; Di Gennaro, K. A.; Saral, R.; Santos, G. W.

    1989-01-01

    The presence of an erythematous skin rash and hemorrhagic complications in acute graft-versus-host disease (GVHD) suggest that the vasculature may be involved in the immunopathologic process. We reviewed endothelial and vascular histopathologic changes on light microscopy and on immunoperoxidase stained sections of skin biopsies obtained from 41 HLA-identical allogeneic marrow transplant recipients with at least grade 2 GVHD. Biopsies taken from 14 allogeneic HLA-identical bone marrow transplant recipients who never developed GVHD were used as controls. Sections were evaluated for evidence of immunologic vascular injury using the rank file analysis of histologic features, expression of HLA-DR antigen, and the distribution of fibrin and factor VIII-related antigen (F VIII RAg). Patients with acute GVHD had significantly greater intimal lymphocytic infiltrates, perivascular nuclear dust deposition, perivascular F VIII Rag extravasation and deposition and vascular proliferation than controls. We find significantly greater endothelial injury in GVHD patients, which may represent primary immunologic injury to the vasculature. The clinical findings in acute GVHD probably result from cumulative endothelial as well as epithelial injury. Images Figure 1 Figure 2 Figure 3 PMID:2596572

  3. Endovascular Treatment in Emergency Setting of Acute Arterial Injuries After Orthopedic Surgery

    SciTech Connect

    Carrafiello, Gianpaolo Fontana, Federico Mangini, Monica Ierardi, Anna Maria Lagana, Domenico; Piacentino, Filippo Vizzari, Francesco Alberto Spano, Emanuela Fugazzola, Carlo

    2012-06-15

    Purpose: To assess the feasibility and effectiveness of emergency endovascular treatment of acute arterial injuries after orthopedic surgery. Materials and Methods: Fifteen patients (mean age 68.3 years) with acute arterial injuries after orthopedic surgery were observed, in particular, 5 patients with pseudoaneurysm, 9 patients with active bleeding, and 1 patient with arterial dissection. Transarterial embolization (TAE) and positioning of covered and noncovered stents were the treatments performed. Follow-up after stent implantation (mean 36 months) was performed with color Doppler US (CDU) at 1, 3, 6, and 12 months and yearly thereafter. Plain X-ray was performed to evidence dislodgment or fracture of the graft. A minimum of 12 months' follow-up is available after TAE. Results: Immediate technical success was obtained in all cases. No major complications occurred. Overall clinical success rate was 100%. During mean follow-up, stent-graft occlusions did not occurred. No recurrence and/or consequence of TAE was registered during a minimum follow-up of 12 months. Conclusions: Percutaneous treatment is a feasible and safe tool for treating arterial injuries because it can provide fast and definitive resolution of the damage. This low-invasiveness approach can be proposed as first-line treatment in patients with acute injuries after orthopedic surgery.

  4. The role of the immune system in central nervous system plasticity after acute injury

    PubMed Central

    Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano

    2014-01-01

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalks between the injured brain and the immune system. In the acute phase, the damaged central nervous system (CNS) activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, which would ultimately bring the inflammatory reaction to a close. In the chronic phase, a sustained immune activation is described in many CNS disorders, and the degree of this prolonged response has variable effects on the spontaneous brain regenerative processes. The challenge for treating acute CNS damages is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Here we have reviewed the available information about the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of recovery after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that ultimately are associated to intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. PMID:24785677

  5. Urinary Biomarkers of Acute Kidney Injury in Patients With Liver Cirrhosis

    PubMed Central

    Ahmed, Qasem Anass; El Sayed, Farag Salama; Emad, Hamed; Mohamed, Emara; Ahmed, Bihery; Heba, Pasha

    2014-01-01

    ABSTRACT Background and aim: Acute kidney injury is a common complication in cirrhotic patients. Serum creatinine is a poor biomarker for detection of renal impairment in cirrhotic patients. The aim of this study was to evaluate Urinary Neutrophils Gelatinase-Associated Lipocalin (NGAL) and Urinary interleukin-18 (IL-18) as early biomarkers of acute kidney injury in cirrhotic patients. Patients and methods: 160 cirrhotic patients was enrolled in this study divided into 3 main groups according to presence or absence of ascites and renal impairment. Results: Significant elevation of both Urinary NGAL and Urinary IL-18 in cirrhotic patients with renal impairment especially in patients with Acute tubular necrosis (ATN) was observed. AUROC was (0.909) with (sensitivity 95.5 %, specificity 76.1) for Urinary NGAL and AUROC was (0.975), with (sensitivity 95.5 %, specificity 91.3 %) for Urinary IL-18. Conclusion: both Urinary NGAL and Urinary IL-18 can act as urinary biomarkers of acute kidney injury in cirrhotic patient PMID:24937940

  6. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    PubMed Central

    2012-01-01

    Objective Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments. PMID:23351279

  7. The role of the immune system in central nervous system plasticity after acute injury.

    PubMed

    Peruzzotti-Jametti, L; Donegá, M; Giusto, E; Mallucci, G; Marchetti, B; Pluchino, S

    2014-12-26

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. PMID:24785677

  8. IL-22 modulates gut epithelial and immune barrier functions following acute alcohol exposure and burn injury

    PubMed Central

    Rendon, Juan L.; Li, Xiaoling; Akhtar, Suhail; Choudhry, Mashkoor A.

    2012-01-01

    Interleukin (IL)–22 maintains gut epithelial integrity and expression of antimicrobial peptides (AMPs) Reg3β and Reg3γ. Our laboratory has shown that acute alcohol/ethanol (EtOH) exposure prior to burn injury results in increased gut permeability, intestinal T cell suppression and enhanced bacterial translocation. Herein, we determined the effect of combined EtOH intoxication and burn injury on intestinal levels of IL-22 as well as Reg3β and Reg3γ expression. We further examined whether in vivo restitution of IL-22 restores gut permeability, Reg3β and Reg3γ levels, and bacterial load (e.g. gut bacterial growth) within the intestine following EtOH and burn injury. Male mice, ~25g, were gavaged with EtOH (2.9 mg/kg) prior to receiving a ~12.5% total body surface area full thickness burn. Mice were immediately treated with saline control or IL-22 (1 mg/kg) by i.p. injection. One day post injury, there was a significant decrease in intestinal IL-22, Reg3β and Reg3γ expression along with an increase in intestinal permeability and gut bacterial load following EtOH combined with burn injury, as compared to sham injury. Treatment with IL-22 normalized Reg3β and Reg3γ expression, and attenuated the increase in intestinal permeability following EtOH and burn injury. Qualitatively, IL-22 treatment reduced the bacterial load in nearly half of mice receiving EtOH combined with burn injury. Our data indicate that IL-22 maintains gut epithelial and immune barrier integrity following EtOH and burn injury; thus, the IL-22/AMP pathway may provide a therapeutic target for the treatment of patients who sustain burn injury under the influence of EtOH. PMID:23143063

  9. Cell-free hemoglobin: a novel mediator of acute lung injury.

    PubMed

    Shaver, Ciara M; Upchurch, Cameron P; Janz, David R; Grove, Brandon S; Putz, Nathan D; Wickersham, Nancy E; Dikalov, Sergey I; Ware, Lorraine B; Bastarache, Julie A

    2016-03-15

    Patients with the acute respiratory distress syndrome (ARDS) have elevated levels of cell-free hemoglobin (CFH) in the air space, but the contribution of CFH to the pathogenesis of acute lung injury is unknown. In the present study, we demonstrate that levels of CFH in the air space correlate with measures of alveolar-capillary barrier dysfunction in humans with ARDS (r = 0.89, P < 0.001) and in mice with ventilator-induced acute lung injury (r = 0.89, P < 0.001). To investigate the specific contribution of CFH to ARDS, we studied the impact of purified CFH in the mouse lung and on cultured mouse lung epithelial (MLE-12) cells. Intratracheal delivery of CFH in mice causes acute lung injury with air space inflammation and alveolar-capillary barrier disruption. Similarly, in MLE-12 cells, CFH increases proinflammatory cytokine expression and increases paracellular permeability as measured by electrical cell-substrate impedance sensing. Next, to determine whether these effects are mediated by the iron-containing heme moiety of CFH, we treated mice with intratracheal hemin, the chloride salt of heme, and found that hemin was sufficient to increase alveolar permeability but failed to induce proinflammatory cytokine expression or epithelial cell injury. Together, these data identify CFH in the air space as a previously unrecognized driver of lung epithelial injury in human and experimental ARDS and suggest that CFH and hemin may contribute to ARDS through different mechanisms. Interventions targeting CFH and heme in the air space could provide a new therapeutic approach for ARDS. PMID:26773065

  10. Cooling an acute muscle injury: can basic scientific theory translate into the clinical setting?

    PubMed

    Bleakley, C M; Glasgow, P; Webb, M J

    2012-03-01

    Ice is commonly used after acute muscle strains but there are no clinical studies of its effectiveness. By comparison, there are a number of basic scientific studies on animals which show that applying ice after muscle injury has a consistent effect on a number of important cellular and physiological events relating to recovery. Some of these effects may be temperature dependant; most animal studies induce significant reductions in muscle temperature at the injury site. The aim of this short report was to consider the cooling magnitudes likely in human models of muscle injury and to discuss its relevance to the clinical setting. Current best evidence shows that muscle temperature reductions in humans are moderate in comparison to most animal models, limiting direct translation to the clinical setting. Further important clinical questions arise when we consider the heterogenous nature of muscle injury in terms of injury type, depth and insulating adipose thickness. Contrary to current practice, it is unlikely that a 'panacea' cooling dose or duration exists in the clinical setting. Clinicians should consider that in extreme circumstances of muscle strain (eg, deep injury with high levels of adipose thickness around the injury site), the clinical effectiveness of cooling may be significantly reduced. PMID:21677317

  11. Platelet-Rich Plasma (PRP) for Acute Muscle Injury: A Systematic Review

    PubMed Central

    A. Hamid, Mohamad Shariff; Yusof, Ashril; Mohamed Ali, Mohamed Razif

    2014-01-01

    Introduction Acute muscle injury is one of the commonest injuries that often result in loss of training and competition time. The best management for muscle injury has not been identified. Sports medicine practitioners used several approaches in attempt to accelerate time to recovery from muscle injury. More recently growing interest focussed on autologous blood product injection. Methods A literature search was conducted systematically using OvidMEDLINE, PubMed, EMBASE, SPORTDiscus and CINAHL databases to retrieve articles published until December 2012. Controlled trials and controlled laboratory studies comparing different strategies to promote early recovery of muscle injury were included. The methodological quality of studies was assessed. Results There are limited studies on the effects of PRP therapy for muscle injury. Three in vivo laboratory studies and one pilot human study were reviewed. The laboratory studies reported histological evidence on significant acceleration of muscle healing in animals treated with autologous conditioned serum (ACS), platelet-rich plasma (PRP) and platelet rich fibrin matrix (PRFM). A pilot human study found athletes treated with repeated ACS injection recovers significantly faster than retrospective controls. Conclusion Several in vivo laboratory studies suggest beneficial effects of ACS, PRP and PRFM in accelerating muscle recovery. Evidence to suggest similar effects on humans is however limited, as valuable information from robust human controlled trials is still not available at this moment. Hence, more studies of satisfactory methodological quality with platelet-rich plasma interventions on muscle injury are justified. PMID:24587389

  12. Traumatic brain injury in children: acute care management.

    PubMed

    Geyer, Kristen; Meller, Karen; Kulpan, Carol; Mowery, Bernice D

    2013-01-01

    The care of the pediatric patient with a severe traumatic brain injury (TBI) is an all-encompassing nursing challenge. Nursing vigilance is required to maintain a physiological balance that protects the injured brain. From the time a child and family first enter the hospital, they are met with the risk of potential death and an uncertain future. The family is subjected to an influx of complex medical and nursing terminology and interventions. Nurses need to understand the complexities of TBI and the modalities of treatment, as well as provide patients and families with support throughout all phases of care. PMID:24640314

  13. Translational toxicological research: investigating and preventing acute lung injury in organophosphorus insecticide poisoning.

    PubMed

    Hulse, Elspeth J; Clutton, R E; Drummond, G; Eddleston, M

    2014-06-01

    Poisoning through ingestion of organophosphorus (OP) insecticide is a leading cause of suicide globally. Severe poisoning with OP compounds creates an unconscious, paralysed patient with respiratory failure. These symptoms make pulmonary aspiration of stomach contents highly likely, potentially causing an acute lung injury. To explore this hypothesis, we created a Gottingen minipig pulmonary aspiration model (n=26) to investigate the mechanism and severity of lung injury created through pulmonary instillation of 0.5 mL/kg mixtures of porcine gastric juice (GJ), OP and/or its solvent. Early results show that aspiration of OP and GJ causes pulmonary neutrophil sequestration, alveolar haemorrhage and interstitial oedema, with disruption of the alveolar-capillary membrane. Further measurements will include quantitative CT imaging, histopathology scoring, acute lung injury biomarkers and respiratory function. In order to test the validity of the minipig model, a pilot study in Sri Lanka has been devised to observe signs of lung injury in human patients who have ingested OP insecticide with or without clinical evidence of pulmonary aspiration. Lung injury will be assessed with PaO2/FIO2 ratios and physiological dead space measurement. Blood, bronchoalveolar lavage and urine will be taken at 24 and 48 h after poisoning and at 3-4 h in surgical control patients to measure acute lung injury biomarkers. An unpublished toxicology study from Sri Lanka, 2011-2012, showed that over 40% of unconscious poisoned patients with a GCS <9 were not intubated for ambulance transfer between rural and district hospitals. Delay in intubation leads to aspiration pneumonitis and pneumonia in 38%-45% of unconscious poisoned patients. We hypothesise that non-drug assisted placement of supraglottic airways may be a good tool for use in unconscious poisoned patients requiring transfer from small rural hospitals in Asia. They could confer better airway protection than no airway intervention

  14. Signaling through the A2B Adenosine Receptor Dampens Endotoxin-Induced Acute Lung Injury

    PubMed Central

    Schingnitz, Ulrich; Hartman, Katherine; MacManus, Christopher F.; Eckle, Tobias; Zug, Stephanie; Colgan, Sean P.; Eltzschig, Holger K.

    2010-01-01

    Sepsis and septic acute lung injury are among the leading causes for morbidity and mortality of critical illness. Extracellular adenosine is a signaling molecule implicated in the cellular adaptation to hypoxia, ischemia or inflammation. Therefore, we pursued the role of the A2B adenosine receptor (A2BAR) as potential therapeutic target in endotoxin-induced acute lung injury. We gained initial insight from in vitro studies of cultured endothelia or epithelia exposed to inflammatory mediators showing time-dependent induction of the A2BAR (up to 12.9±3.4-fold, p<0.05). Similarly, murine studies of endotoxin-induced lung injury identified an almost 4.6-fold induction of A2BAR transcript and corresponding protein induction with LPS-exposure. Studies utilizing A2BAR promoter constructs and RNA-protection assays indicated that A2BAR induction involved mRNA stability. Functional studies of LPS-induced lung injury revealed that pharmacological inhibition or genetic deletion of the A2BAR was associated with dramatic increases in lung inflammation and histologic tissue injury. Studies of A2BAR-bone marrow chimeric mice suggested pulmonary A2BAR signaling in lung protection. Finally, studies with a specific A2BAR agonist (BAY 60-6583) demonstrated attenuation of lung inflammation and pulmonary edema in wild-type but not in gene-targeted mice for the A2BAR. These studies suggest the A2BAR as potential therapeutic target in the treatment of endotoxin-induced forms of acute lung injury. PMID:20348420

  15. Neuron specific enolase: a promising therapeutic target in acute spinal cord injury.

    PubMed

    Haque, Azizul; Ray, Swapan K; Cox, April; Banik, Naren L

    2016-06-01

    Enolase is a multifunctional protein, which is expressed abundantly in the cytosol. Upon stimulatory signals, enolase can traffic to cell surface and contribute to different pathologies including injury, autoimmunity, infection, inflammation, and cancer. Cell-surface expression of enolase is often detected on activated macrophages, microglia/macrophages, microglia, and astrocytes, promoting extracellular matrix degradation, production of pro-inflammatory cytokines/chemokines, and invasion of inflammatory cells in the sites of injury and inflammation. Inflammatory stimulation also induces translocation of enolase from the cytosolic pool to the cell surface where it can act as a plasminogen receptor and promote extracellular matrix degradation and tissue damage. Spinal cord injury (SCI) is a devastating debilitating condition characterized by progressive pathological changes including complex and evolving molecular cascades, and insights into the role of enolase in multiple inflammatory events have not yet been fully elucidated. Neuronal damage following SCI is associated with an elevation of neuron specific enolase (NSE), which is also known to play a role in the pathogenesis of hypoxic-ischemic brain injury. Thus, NSE is now considered as a biomarker in ischemic brain damage, and it has recently been suggested to be a biomarker in traumatic brain injury (TBI), stroke and anoxic encephalopathy after cardiac arrest and acute SCI as well. This review article gives an overview of the current basic research and clinical studies on the role of multifunctional enolase in neurotrauma, with a special emphasis on NSE in acute SCI. PMID:26847611

  16. Role of hepatic resident and infiltrating macrophages in liver repair after acute injury.

    PubMed

    You, Qiang; Holt, Michael; Yin, Hao; Li, Guiying; Hu, Cheng-Jun; Ju, Cynthia

    2013-09-15

    Treatment of liver disease, caused by hepatotoxins, viral infections, alcohol ingestion, or autoimmune conditions, remains challenging and costly. The liver has a powerful capacity to repair and regenerate, thus a thorough understanding of this tightly orchestrated process will undoubtedly improve clinical means of restoring liver function after injury. Using a murine model of acute liver injury caused by overdose of acetaminophen (APAP), our studies demonstrated that the combined absence of liver resident macrophages (Kupffer cells, KCs), and infiltrating macrophages (IMs) resulted in a marked delay in liver repair, even though the initiation and extent of peak liver injury was not impacted. This delay was not due to impaired hepatocyte proliferation but rather prolonged vascular leakage, which is caused by APAP-induced liver sinusoidal endothelial cell (LSEC) injury. We also found that KCs and IMs express an array of angiogenic factors and induce LSEC proliferation and migration. Our mechanistic studies suggest that hypoxia-inducible factor (HIF) may be involved in regulating the angiogenic effect of hepatic macrophages (Macs), as we found that APAP challenge resulted in hypoxia and stabilization of HIF in the liver and hepatic Macs. Together, these data indicate an important role for hepatic Macs in liver blood vessel repair, thereby contributing to tissue recovery from acute injury. PMID:23876342

  17. Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities

    PubMed Central

    Yu, Chen; Qi, Dong; Sun, Ju-Feng; Li, Peng; Fan, Hua-Ying

    2015-01-01

    This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury. PMID:26149595

  18. Loxosceles gaucho Venom-Induced Acute Kidney Injury – In Vivo and In Vitro Studies

    PubMed Central

    Lucato, Rui V.; Abdulkader, Regina C. R. M.; Barbaro, Katia C.; Mendes, Glória E.; Castro, Isac; Baptista, Maria A. S. F.; Cury, Patrícia M.; Malheiros, Denise M. C.; Schor, Nestor; Yu, Luis; Burdmann, Emmanuel A.

    2011-01-01

    Background Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. Methodology/Principal Findings In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. Conclusions/Significance Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite. PMID:21655312

  19. Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality.

    PubMed

    Conroy, Andrea L; Hawkes, Michael; Elphinstone, Robyn E; Morgan, Catherine; Hermann, Laura; Barker, Kevin R; Namasopo, Sophie; Opoka, Robert O; John, Chandy C; Liles, W Conrad; Kain, Kevin C

    2016-03-01

    Background.  Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods.  One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results.  Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03-1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65-.95; P = .006) and 0.72 (95% CI, .57-.87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively). Conclusions.  Acute kidney injury is an underrecognized complication in young children with SM

  20. Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality

    PubMed Central

    Conroy, Andrea L.; Hawkes, Michael; Elphinstone, Robyn E.; Morgan, Catherine; Hermann, Laura; Barker, Kevin R.; Namasopo, Sophie; Opoka, Robert O.; John, Chandy C.; Liles, W. Conrad; Kain, Kevin C.

    2016-01-01

    Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results. Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03–1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65–.95; P = .006) and 0.72 (95% CI, .57–.87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively). Conclusions. Acute kidney injury is an underrecognized complication in young children with SM

  1. Specialized Respiratory Management for Acute Cervical Spinal Cord Injury:

    PubMed Central

    Wong, Sandra Lynn; Shem, Kazuko; Crew, James

    2012-01-01

    Background: In individuals with cervical spinal cord injury (SCI), respiratory complications arise within hours to days of injury. Paralysis of the respiratory muscles predisposes the patient toward respiratory failure. Respiratory complications after cervical SCI include hypoventilation, hypercapnea, reduction in surfactant production, mucus plugging, atelectasis, and pneumonia. Ultimately, the patient must use increased work to breathe, which results in respiratory fatigue and may eventually require intubation for mechanical ventilation. Without specialized respiratory management for individuals with tetraplegia, recurrent pneumonias, bronchoscopies, and difficulty in maintaining a stable respiratory status will persist. Objective: This retrospective analysis examined the effectiveness of specialized respiratory management utilized in a regional SCI center. Methods: Individuals with C1-C4 SCI (N = 24) were the focus of this study as these neurological levels present with the most complicated respiratory status. Results: All of the study patients’ respiratory status improved with the specialized respiratory management administered in the SCI specialty unit. For a majority of these patients, respiratory improvements were noted within 1 week of admission to our SCI unit. Conclusion: Utilization of high tidal volume ventilation, high frequency percussive ventilation, and mechanical insufflation– exsufflation have demonstrated efficacy in stabilizing the respiratory status of these individuals. Optimizing respiratory status enables the patients to participate in rehabilitation therapies, allows for the opportunity to vocalize, and results in fewer days on mechanical ventilation for patients who are weanable. PMID:23459555

  2. Role of fibrinogen in acute ischemic kidney injury.

    PubMed

    Sörensen-Zender, I; Rong, S; Susnik, N; Lange, J; Gueler, F; Degen, J L; Melk, A; Haller, H; Schmitt, R

    2013-09-01

    Renal ischemia-reperfusion (I/R) is associated with activation of the coagulation system and accumulation of blood clotting factors in the kidney. The aim of the present study was to examine the functional impact of fibrinogen on renal inflammation, damage, and repair in the context of I/R injury. In this study, we found that I/R was associated with a significant increase in the renal deposition of circulating fibrinogen. In parallel, I/R stress induced the de novo expression of fibrinogen in tubular epithelial cells, as reflected by RT-PCR, immunofluorescence, and in situ hybridization. In vitro, fibrinogen expression was induced by oncostatin M and hyper-IL-6 in primary tubular epithelial cells, and fibrinogen-containing medium had an inhibitory effect on tubular epithelial cell adhesion and migration. Fibrinogen(+/-) mice showed similar survival as wild-type mice but better preservation in early postischemic renal function. In fibrinogen(-/-) mice, renal function and survival were significantly worse than in fibrinogen(+/-) mice. Renal transplant experiments revealed reduced expression of tubular damage markers and attenuated proinflammatory cytokine expression but increased inflammatory cell infiltrates and transforming growth factor-β expression in fibrinogen(-/-) isografts. These data point to heterogeneous effects of fibrinogen in renal I/R injury. While a complete lack of fibrinogen may be detrimental, partial reduction of fibrinogen in heterozygous mice can improve renal function and overall outcome. PMID:23804451

  3. Review of Acute Traumatic Closed Mallet Finger Injuries in Adults

    PubMed Central

    Salazar Botero, Santiago; Hidalgo Diaz, Juan Jose; Benaïda, Anissa; Collon, Sylvie; Facca, Sybille

    2016-01-01

    In adults, mallet finger is a traumatic zone I lesion of the extensor tendon with either tendon rupture or bony avulsion at the base of the distal phalanx. High-energy mechanisms of injury generally occur in young men, whereas lower energy mechanisms are observed in elderly women. The mechanism of injury is an axial load applied to a straight digit tip, which is then followed by passive extreme distal interphalangeal joint (DIPJ) hyperextension or hyperflexion. Mallet finger is diagnosed clinically, but an X-ray should always be performed. Tubiana's classification takes into account the size of the bony articular fragment and DIPJ subluxation. We propose to stage subluxated fractures as stage III if the subluxation is reducible with a splint and as stage IV if not. Left untreated, mallet finger becomes chronic and leads to a swan-neck deformity and DIPJ osteoarthritis. The goal of treatment is to restore active DIPJ extension. The results of a six- to eight-week conservative course of treatment with a DIPJ splint in slight hyperextension for tendon lesions or straight for bony avulsions depends on patient compliance. Surgical treatments vary in terms of the approach, the reduction technique, and the means of fixation. The risks involved are stiffness, septic arthritis, and osteoarthritis. Given the lack of consensus regarding indications for treatment, we propose to treat all cases of mallet finger with a dorsal glued splint except for stage IV mallet finger, which we treat with extra-articular pinning. PMID:27019806

  4. Neurogenic stunned myocardium - do we consider this diagnosis in patients with acute central nervous system injury and acute heart failure?

    PubMed

    Mierzewska-Schmidt, Magdalena; Gawecka, Agnieszka

    2015-01-01

    Neurogenic stunned myocardium (NSM) is defined as myocardial injury and dysfunction of a sudden onset, occurring after various types of acute brain injury as a result of an imbalance in the autonomic nervous system. The typical spectrum of clinically observed abnormalities includes acute left ventricular failure, not uncommonly progressing to cardiogenic shock with hypotension that requires inotropic agents, pulmonary oedema and various arrhythmias. Commonly-seen electrocardiographic changes include: prolonged QT interval, ST segment changes, T-wave inversion, a new Q-wave or U-wave. Echocardiography shows both an impaired both systolic and diastolic function of the left ventricle. Biochemical markers of NSM comprise metabolic acidosis and increased cardiac enzymes and markers: creatine kinase (CK), and CK-MB, troponin I and B-type natriuretic peptide. The main cause of NSM is myocardial injury induced by local catecholamine release from nerve endings within the myocardium. Recently, a theory has been proposed to classify NSM as one of the stress-related cardiomyopathies, together with Takotsubo cardiomyopathy, acute left ventricular failure in the critically ill, cardiomyopathy associated with pheochromacytoma and exogenous catecholamine administration. The occurrence of NSM increases the risk of life-threatening complications, death, and worsens neurologic outcome. As far as we know, treatment should generally focus on the underlying neurologic process in order to maximize neurologic recovery. Improvement in neurologic pathology leads to rapid improvement in cardiac function and its full recovery, as NSM is a fully reversible condition if the patient survives. Awareness of the existence of NSM and a deeper knowledge of its etiopathology may reduce diagnostic errors, optimise its treatment. PMID:25940334

  5. Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury.

    PubMed

    Choi, Iee Ho; Hwang, Pyoung Han; Choi, Sam Im; Lee, Dae Yeol; Kim, Min Sun

    2016-09-01

    Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days after his return from the journey. Urinalysis showed pyuria and hematuria. Blood examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were performed for 19 hospital days. Falciparum malaria was then confirmed by peripheral blood smear, and antimalarial medications were initiated. The patient's condition and laboratory results were quickly normalized. We report a case of severe acute renal failure associated with delayed diagnosis of falciparum malaria, and primary use of supportive treatment rather than antimalarial medicine. The present case suggests that early diagnosis and treatment is important because untreated tropical malaria can be associated with severe acute renal failure and fatality. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history of endemic areas. PMID:27510397

  6. Nonapoptotic cell death in acute kidney injury and transplantation.

    PubMed

    Linkermann, Andreas

    2016-01-01

    Acute tubular necrosis causes a loss of renal function, which clinically presents as acute kidney failure (AKI). The biochemical signaling pathways that trigger necrosis have been investigated in detail over the past 5 years. It is now clear that necrosis (regulated necrosis, RN) represents a genetically driven process that contributes to the pathophysiology of AKI. RN pathways such as necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-induced regulated necrosis (MPT-RN) may be mechanistically distinct, and the relative contributions to overall organ damage during AKI in living organisms largely remain elusive. In a synchronized manner, some necrotic programs induce the breakdown of tubular segments and multicellular functional units, whereas others are limited to killing single cells in the tubular compartment. Importantly, the means by which a renal cell dies may have implications for the subsequent inflammatory response. In this review, the recent advances in the field of renal cell death in AKI and key enzymes that might serve as novel therapeutic targets will be discussed. As a consequence of the interference with RN, the immunogenicity of dying cells in AKI in renal transplants will be diminished, rendering inhibitors of RN indirect immunosuppressive agents. PMID:26759047

  7. Acute kidney injury and disseminated intravascular coagulation due to mercuric chloride poisoning.

    PubMed

    Dhanapriya, J; Gopalakrishnan, N; Arun, V; Dineshkumar, T; Sakthirajan, R; Balasubramaniyan, T; Haris, M

    2016-01-01

    Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI) and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (DIC). Renal biopsy showed acute tubular necrosis. Later, the consumed substance was proven to be mercuric chloride. His renal failure improved over time, and his creatinine normalized after 2 months. PMID:27194836

  8. Acute kidney injury and disseminated intravascular coagulation due to mercuric chloride poisoning

    PubMed Central

    Dhanapriya, J.; Gopalakrishnan, N.; Arun, V.; Dineshkumar, T.; Sakthirajan, R.; Balasubramaniyan, T.; Haris, M.

    2016-01-01

    Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI) and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (DIC). Renal biopsy showed acute tubular necrosis. Later, the consumed substance was proven to be mercuric chloride. His renal failure improved over time, and his creatinine normalized after 2 months. PMID:27194836

  9. Prevention of acute knee injuries in adolescent female football players: cluster randomised controlled trial

    PubMed Central

    Atroshi, Isam; Magnusson, Henrik; Wagner, Philippe; Hägglund, Martin

    2012-01-01

    Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players. Design Stratified cluster randomised controlled trial with clubs as the unit of randomisation. Setting 230 Swedish football clubs (121 in the intervention group, 109 in the control group) were followed for one season (2009, seven months). Participants 4564 players aged 12-17 years (2479 in the intervention group, 2085 in the control group) completed the study. Intervention 15 minute neuromuscular warm-up programme (targeting core stability, balance, and proper knee alignment) to be carried out twice a week throughout the season. Main outcome measures The primary outcome was rate of anterior cruciate ligament injury; secondary outcomes were rates of severe knee injury (>4 weeks’ absence) and any acute knee injury. Results Seven players (0.28%) in the intervention group, and 14 (0.67%) in the control group had an anterior cruciate ligament injury. By Cox regression analysis according to intention to treat, a 64% reduction in the rate of anterior cruciate ligament injury was seen in the intervention group (rate ratio 0.36, 95% confidence interval 0.15 to 0.85). The absolute rate difference was −0.07 (95% confidence interval −0.13 to 0.001) per 1000 playing hours in favour of the intervention group. No significant rate reductions were seen for secondary outcomes. Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players. However, the absolute rate difference did not reach statistical significance, possibly owing to the small number of events. Trial registration Clinical trials NCT00894595. PMID:22556050

  10. Nrf2 activation prevents cadmium-induced acute liver injury

    SciTech Connect

    Wu, Kai C.; Liu, Jie J.; Klaassen, Curtis D.

    2012-08-15

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H{sub 2}DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice

  11. Ethanol Potentiates the Acute Fatty Infiltration of Liver Caused by Burn Injury: Prevention by Insulin Treatment

    PubMed Central

    Emanuele, Nicholas V.; Emanuele, Mary Ann; Morgan, Michelle O.; Sulo, Denise; Yong, Sheri; Kovacs, Elizabeth J.; Himes, Ryan D.; Callaci, John J.

    2011-01-01

    Burn injury is a significant and severe representation of critical illness. Nearly, 50% of patients admitted to hospitals for burn injuries have detectable levels of ethanol in their circulations and these patients have poorer clinical outcomes than burned individuals without measurable circulating ethanol. We report here data on a clinically relevant form of hepatic injury, the development of microvesicular steatosis, in a murine model wherein animals were either given ethanol or saline, and were subjected to burn or sham injury. Because better glycemic control with insulin has been shown in clinical studies to impart major clinical benefit, an additional group of burn ethanol animals were treated with insulin. Insulin significantly reduced blood glucose in injured animals to levels no different from those seen in animals that were neither ethanol exposed nor burned. A single intraperitoneal injection of ethanol was insufficient to raise blood alanine aminotransferase (ALT), measured as an index of liver injury. However, burn injury led to significant increases in ALT at 24 and 48 hours, which had returned to preinjury levels by 7 days. This ALT rise was completely prevented with insulin treatment. A single injection of ethanol did not evoke increased microvesicular steatosis but did potentiate the ability of burn to do so at 24 hours after injury. The burn induced increase in microvesicular steatosis was also seen at 48 hours, but had subsided by 7 days. The increased microvesicular steatosis was prevented by insulin therapy. Thus, ethanol potentiates the ability of burn to cause acute liver injury, which is completely preventable by insulin therapy. These findings may have substantial clinical significance and suggest this model may be useful for the study of the mechanisms of hepatic injury as well as the mechanisms, probably multiple, of insulin action in this setting. PMID:19349879

  12. Assessment of Plasma and NGAL for the Early Prediction of Acute Kidney Injury After Cardiac Surgery in Adults Study

    ClinicalTrials.gov

    2016-04-11

    Acute Kidney Injury (AKI); Chronic Kidney Disease (CKD); End Stage Renal Disease (ESRD); Estimated Glomerular Filtration Rate (eGFR); Neutrophil Gelatinase-associated Lipocalin (NGAL); Serum Creatinine (SCr); Urine Creatinine (UCr); Urine Albumin (UAlb)

  13. Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury

    PubMed Central

    Devarajan, Prasad

    2010-01-01

    Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which depends on serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers has crippled our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase-associated lipocalin, arguably the most promising novel AKI biomarker, are reviewed in this article. Neutrophil gelatinase-associated lipocalin is emerging as an excellent standalone troponin-like biomarker in the plasma and urine for the prediction of AKI, monitoring clinical trials in AKI and for the prognosis of AKI in several common clinical scenarios. PMID:20406069

  14. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    NASA Astrophysics Data System (ADS)

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  15. Acute lung injury after platelet transfusion in a patient with dengue fever

    PubMed Central

    Karoli, Ritu; Bhat, Sanjay; Fatima, Jalees; Verma, Pankaj

    2014-01-01

    Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome associated with the transfusion of plasmacontaining blood components. Recently, TRALI has come to be recognized as the leading cause of transfusion-related mortality. This complication typically presents as shortness of breath, hypoxemia, hypotension, fever, and non cardiogenic pulmonary edema, occurring within 6 h after transfusion. Although the mechanism of TRALI has not been exactly known, it has been associated with human leukocyte antigen antibodies and with biologically active mediators in stored cellular blood components. We, hereby, present a case of a patient with dengue fever who developed acute lung injury (ALI), presumably TRALI, after transfusion of platelet concentrates. He was treated with supportive measures and mechanical ventilation. Greater knowledge and increased awareness especially amongst the clinicians regarding TRALI is needed for prevention and treatment of this potentially severe complication of blood/component transfusion. PMID:25161356

  16. Severe starvation-induced hepatocyte autophagy as a cause of acute liver injury in anorexia nervosa: a case report.

    PubMed

    Restellini, S; Spahr, L; Rubbia Brandt, L

    2013-01-01

    Introduction. Mild elevation of transaminase may be observed in anorexia nervosa, but acute liver injury is uncommon. A complex programmed cell death in response to starvation, called autophagy, has been described in experimental and human studies. Case Presentation. A 24-year-old woman suffering from anorexia nervosa was hospitalized for severe malnutrition. At admission, there were biological signs of acute liver injury but no electrolytic imbalance. After having ruled out the most common causes of liver injury, the patient was carefully refed. As liver tests remained abnormal, liver biopsy was performed. At histology and electron microscopy, numerous signs suggestive of starvation-induced hepatocyte autophagy were found. Discussion. Severe starvation can be associated with acute liver injury that is slowly reversible with careful enteral nutrition. In this clinical situation, profound hepatic glycogen depletion in association with autophagy appears as the leading cause of liver injury. PMID:25379300

  17. Rhabdomyolysis and acute kidney injury in dengue fever.

    PubMed

    Mishra, Arvind; Singh, Varun Kumar; Nanda, Satyan

    2015-01-01

    Rhabdomyolysis is a rare but potentially lethal complication of severe dengue fever. We present a case of 21-year-old man with fever, bodyache and black coloured and decreasing amount of urine. He was positive for NS1 (non-structural protein-1) antigen and IgM antibody for dengue. Platelet count was below 20 × 10(9)/L and kidney function test was deranged. Urine was positive for myoglobin. The patient was managed emergently on conservative lines and improved in 10 days. Rhabdomyolysis should always be kept in mind in a patient with severe dengue, as its early detection and prompt management can prevent further progression to acute renal failure. PMID:26174727

  18. Excellent reliability for MRI grading and prognostic parameters in acute hamstring injuries

    PubMed Central

    Hamilton, B; Whiteley, R; Almusa, E; Roger, B; Geertsema, C; Tol, Johannes L

    2014-01-01

    Background Categorical grading and other measurable MRI parameters are frequently utilised for predicting the outcome of hamstring injuries. However, the reliability and smallest detectable difference (SDD) have not been previously evaluated. It therefore remains unclear if the variability in previously reported results reflects reporting variation or actual injury status. Methods 25 hamstring injuries were scored by two experienced radiologists using the Peetrons grading and specific prognostic MRI parameters: distance from ischial tuberosity (cm), extent (cranio to caudal, anterior to posterior, medial to lateral; (cm)), maximum cross-sectional area (%), volume (cm3) of the oedema. The interobserver and intraobserver reliability was calculated along with the SDDs for each scale variable. Results There were 3 Grade 0 (12%), 11 grade 1 (44%), 9 grade 2 (36%) and 2 grade 3 (8%) injuries. Cronbach's α values for grading were 1.00 (inter) and 0.96 (intra), respectively. The intraclass correlation coefficients for the prognostic MRI parameters were between 0.77 and 1.0. The SDDs varied between each parameter. Conclusions Excellent interobserver and intraobserver reliability was found for grading and prognostic MRI parameters in acute hamstring injuries. In daily practice and research, we can be confident that scoring hamstring injuries by experienced radiologists is reproducible. The documented SDDs allow meaningful clinical inferences to be made when assessing observed and reported changes in MRI status. PMID:24037670

  19. ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial ischemia/reperfusion injury in mice

    PubMed Central

    Gandhi, Chintan; Motto, David G.; Jensen, Melissa; Lentz, Steven R.

    2012-01-01

    Epidemiologic studies suggest that elevated VWF levels and reduced ADAMTS13 activity in the plasma are risk factors for myocardial infarction. However, it remains unknown whether the ADAMTS13-VWF axis plays a causal role in the pathophysiology of myocardial infarction. In the present study, we tested the hypothesis that ADAMTS13 reduces VWF-mediated acute myocardial ischemia/reperfusion (I/R) injury in mice. Infarct size, neutrophil infiltration, and myocyte apoptosis in the left ventricular area were quantified after 30 minutes of ischemia and 23.5 hours of reperfusion injury. Adamts13−/− mice exhibited significantly larger infarcts concordant with increased neutrophil infiltration and myocyte apoptosis compared with wild-type (WT) mice. In contrast, Vwf−/− mice exhibited significantly reduced infarct size, neutrophil infiltration, and myocyte apoptosis compared with WT mice, suggesting a detrimental role for VWF in myocardial I/R injury. Treating WT or Adamts13−/− mice with neutralizing Abs to VWF significantly reduced infarct size compared with control Ig–treated mice. Finally, myocardial I/R injury in Adamts13−/−/Vwf−/− mice was similar to that in Vwf−/− mice, suggesting that the exacerbated myocardial I/R injury observed in the setting of ADAMTS13 deficiency is VWF dependent. These findings reveal that ADAMTS13 and VWF are causally involved in myocardial I/R injury. PMID:22983446

  20. A case of acute kidney injury from crystal nephropathy secondary to pomalidomide and levofloxacin use.

    PubMed

    Baird, Phylicia; Leung, Sam; Hoang, Huy; Babalola, Olawumi; Devoe, Craig E; Wanchoo, Rimda; Jhaveri, Kenar D

    2016-04-01

    Pomalidomide is an analog of thalidomide with immunomodulatory, anti-angiogenic, and anti-neoplastic activity indicated for the treatment of multiple myeloma refractory to at least two prior therapies. The incidence for renal failure was <5% in a single phase II study of pomalidomide and dexamethasone in patients with multiple myeloma that failed both lenalidomide and bortezomib therapy. We report a case suggesting crystal nephropathy as the mechanism for acute kidney injury in pomalidomide and fluoroquinolone use. PMID:25591868

  1. Horizontal and Vertical Stabilization of Acute Unstable Acromioclavicular Joint Injuries Arthroscopy-Assisted

    PubMed Central

    Cisneros, Luis Natera; Sarasquete Reiriz, Juan; Besalduch, Marina; Petrica, Alexandru; Escolà, Ana; Rodriguez, Joaquim; Fallone, Jan Carlo

    2015-01-01

    We describe the technical aspects of an arthroscopy-assisted procedure indicated for the management of acute unstable acromioclavicular joint injuries, consisting of a synthetic augmentation of both the coracoclavicular and acromioclavicular ligaments, that anatomically reproduces the coracoclavicular biomechanics and offers fixation that keeps the torn ends of the ligaments facing one another, thus allowing healing of the native structures without the need for a second surgical procedure for metal hardware removal. PMID:26870653

  2. Sympathomimetic syndrome, choreoathetosis, and acute kidney injury following "bath salts" injection.

    PubMed

    Sutamtewagul, Grerk; Sood, Vineeta; Nugent, Kenneth

    2014-01-01

    "Bath salts" is a well known street drug which can cause several cardiovascular and neuropsychiatric symptoms. However, only one case of acute kidney injury has been reported in the literature. We present a case with sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury following the use of bath salts. A 37-year-old man with past medical history of hypertension and depression was brought to the emergency center with body shaking. Three days before admission he injected 3 doses of bath salts intravenously and felt eye pain with blurry vision followed by a metallic taste, strange smells, profuse sweating, and body shaking. At presentation he had a sympathomimetic syndrome including high blood pressure, tachycardia, tachypnea, and hyperhydrosis with choreoathetotic movements. Laboratory testing revealed leukocytosis and acute kidney injury with a BUN of 95 mg/ dL and a creatinine of 15.2 mg/dL. Creatine kinase was 4,457 IU/dL. Urine drug screen is negative for amphetamine, cannabinoids, and cocaine; blood alcohol level was zero. During his ICU stay he became disoriented and agitated. Supportive treatment with 7.2 liters of intravenous fluid over 3 days, haloperidol, and lorazepam gradually improved his symptoms and his renal failure. Bath salts contain 3,4-methylenedioxypyrovalerone, a psychoactive norepinephrine and dopamine reuptake inhibitor. Choreoathetosis in this patient could be explained through dopaminergic effect of bath salts or uremic encephalopathy. The mechanism for acute kidney injury from bath salts may involve direct drug effects though norepinephrine and dopamine-induced vasoconstriction (renal ischemia), rhabdomyolysis, hyperthermia, and/or volume contraction. PMID:24356039

  3. Ileal Neobladder With Mucous Plugs as a Cause of Obstructive Acute Kidney Injury Requiring Emergent Hemodialysis.

    PubMed

    Singla, Montish; Shikha, Deep; Lee, Sunggeun; Baumstein, Donald; Chaudhari, Ashok; Carbajal, Roger

    2016-01-01

    Ileal neobladder is the preferred technique in the management of urinary diversion postradical cystectomy for bladder malignancy. The common complications associated with this procedure are atrophied kidney, chronic pyelonephritis, decreased renal function, ureteroileal or urethral anastomotic site stricture, urinary tract stones, incontinence, and hyperchloremic metabolic acidosis. Mucous plugs are also seen in 2%-3% patients. We present a rare presentation of a patient who required hemodialysis for severe hyperkalemia and acute kidney injury caused by mucous plugging of ileal neobladder. PMID:25420078

  4. Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury.

    PubMed

    Lankadeva, Yugeesh R; Kosaka, Junko; Evans, Roger G; Bailey, Simon R; Bellomo, Rinaldo; May, Clive N

    2016-07-01

    Norepinephrine is the principal vasopressor used to restore blood pressure in sepsis, but its effects on intrarenal oxygenation are unknown. To clarify this, we examined renal cortical, medullary, and urinary oxygenation in ovine septic acute kidney injury and the response to resuscitation with norepinephrine. A renal artery flow probe and fiberoptic probes were placed in the cortex and medulla of sheep to measure tissue perfusion and oxygenation. A probe in the bladder catheter measured urinary oxygenation. Sepsis was induced in conscious sheep by infusion of Escherichia coli for 32 hours. At 24 to 30 hours of sepsis, either norepinephrine, to restore mean arterial pressure to preseptic levels or vehicle-saline was infused (8 sheep per group). Septic acute kidney injury was characterized by a reduction in blood pressure of ∼12 mm Hg, renal hyperperfusion, and oliguria. Sepsis reduced medullary perfusion (from an average of 1289 to 628 blood perfusion units), medullary oxygenation (from 32 to 16 mm Hg), and urinary oxygenation (from 36 to 24 mm Hg). Restoring blood pressure with norepinephrine further reduced medullary perfusion to an average of 331 blood perfusion units, medullary oxygenation to 8 mm Hg and urinary oxygenation to 18 mm Hg. Cortical perfusion and oxygenation were preserved. Thus, renal medullary hypoxia caused by intrarenal blood flow redistribution may contribute to the development of septic acute kidney injury, and resuscitation of blood pressure with norepinephrine exacerbates medullary hypoxia. The parallel changes in medullary and urinary oxygenation suggest that urinary oxygenation may be a useful real-time biomarker for risk of acute kidney injury. PMID:27165831

  5. Social benefit payments and acute injury among low-income mothers

    PubMed Central

    Redelmeier, Donald A; Chan, William K; Mullainathan, Sendhil; Shafir, Eldar

    2012-01-01

    Background Human error due to risky behaviour is a common and important contributor to acute injury related to poverty. We studied whether social benefit payments mitigate or exacerbate risky behaviours that lead to emergency visits for acute injury among low-income mothers with dependent children. Methods We analyzed total emergency department visits throughout Ontario to identify women between 15 and 55 years of age who were mothers of children younger than 18 years, who were living in the lowest socio-economic quintile and who presented with acute injury. We used universal health care databases to evaluate emergency department visits during specific days on which social benefit payments were made (child benefit distribution) relative to visits on control days over a 7-year interval (1 April 2003 to 31 March 2010). Results A total of 153 377 emergency department visits met the inclusion criteria. We observed fewer emergencies per day on child benefit payment days than on control days (56.4 v. 60.1, p = 0.008). The difference was primarily explained by lower values among mothers age 35 years or younger (relative reduction 7.29%, 95% confidence interval [CI] 1.69% to 12.88%), those living in urban areas (relative reduction 7.07%, 95% CI 3.05% to 11.10%) and those treated at community hospitals (relative reduction 6.83%, 95% CI 2.46% to 11.19%). No significant differences were observed for the 7 days immediately before or the 7 days immediately after the child benefit payment. Interpretation Contrary to political commentary, we found that small reductions in relative poverty mitigated, rather than exacerbated, risky behaviours that contribute to acute injury among low-income mothers with dependent children. PMID:23687523

  6. Efficacy and safety of mesenchymal stromal cells in preclinical models of acute lung injury: a systematic review protocol

    PubMed Central

    2014-01-01

    Background Acute respiratory distress syndrome (ARDS) in humans is caused by an unchecked proinflammatory response that results in diffuse and severe lung injury, and it is associated with a mortality rate of 35 to 45%. Mesenchymal stromal cells (MSCs; ‘adult stem cells’) could represent a promising new therapy for this syndrome, since preclinical evidence suggests that MSCs may ameliorate lung injury. Prior to a human clinical trial, our aim is to conduct a systematic review to compare the efficacy and safety of MSC therapy versus controls in preclinical models of acute lung injury that mimic some aspects of the human ARDS. Methods/Design We will include comparative preclinical studies (randomized and non-randomized) of acute lung injury in which MSCs were administered and outcomes compared to animals given a vehicle control. The primary outcome will be death. Secondary outcomes will include the four key features of preclinical acute lung injury as defined by the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar capillary barrier, lung inflammatory response, and physiological dysfunction) and pathogen clearance for acute lung injury models that are caused by infection. Electronic searches of MEDLINE, Embase, BIOSIS Previews, and Web of Science will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently and in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the Cochrane risk of bias tool, and individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Discussion The results of this systematic review will comprehensively summarize the safety and efficacy of MSC therapy in preclinical models of acute lung injury. Our results will help translational scientists and

  7. Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor

    PubMed Central

    Urich, Daniela; Soberanes, Saul; Manghi, Tomas S.; Chiarella, Sergio E.; Chandel, Navdeep S.; Budinger, G. R. Scott; Mutlu, Gökhan M.

    2012-01-01

    Objective Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients with alcoholism. We have recently shown increased levels of lung adenosine inhibit alveolar fluid clearance, an important predictor of outcome in patients with ARDS. We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na+ transport in the lung. Methods We treated wild-type mice with alcohol administered i.p. to achieve blood alcohol levels associated with moderate to severe intoxication and measured the rate of alveolar fluid clearance and Na,K-ATPase expression in peripheral lung tissue and assessed the effect of alcohol on survival during exposure to hyperoxia. We used primary rat alveolar type II cells to investigate the mechanisms by which alcohol regulates alveolar Na+ transport. Results Exposure to alcohol reduced alveolar fluid clearance, downregulated Na,K-ATPase in the lung tissue and worsened hyperoxia-induced lung injury. Alcohol caused an increase in BAL fluid adenosine levels. A similar increase in lung adenosine levels was observed after exposure to hyperoxia. In primary rat alveolar type II cells alcohol and adenosine decreased the abundance of the Na,K-ATPase at the basolateral membrane via a mechanism that required activation of the AMPK. Conclusions Alcohol decreases alveolar fluid clearance and impairs survival from acute lung injury. Alcohol induced increases in lung adenosine levels may be responsible for reduction in alveolar fluid clearance and associated worsening of lung injury. PMID:22272351

  8. Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

    PubMed Central

    McCullough, Emily H.; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L.; Dobos, Julie A.; Brett, Christopher A.; Santarsieri, Martina; Dixon, C. Edward; Berga, Sarah L.; Fabio, Anthony

    2011-01-01

    Abstract Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global

  9. Superoxide Mediates Acute Liver Injury in Irradiated Mice Lacking Sirtuin 3

    PubMed Central

    Coleman, Mitchell C.; Olivier, Alicia K.; Jacobus, James A.; Mapuskar, Kranti A.; Mao, Gaowei; Martin, Sean M.; Riley, Dennis P.; Gius, David

    2014-01-01

    Abstract Aims: This study determined whether acute radiation-induced liver injury seen in Sirtuin3−/− mice after exposure to Cs-137 γ-rays was mediated by superoxide anion (O2•−). Results: Male wild-type (WT) and SIRT3−/− mice were given 2×2 Gy whole-body radiation doses separated by 24 h and livers were harvested 20 h after the second dose. Ex vivo measurements in fresh frozen liver sections demonstrated 50% increases in dihydroethidium oxidation from SIRT3−/− animals, relative to WT animals, before irradiation, but this increase was not detected 20 h after radiation exposure. In addition, irradiated livers from SIRT3−/− animals showed significant hydropic degeneration, loss of MitoTracker Green FM staining, increased immunohistochemical staining for 3-nitrotyrosine, loss of Ki67 staining, and increased mitochondrial localization of p53. These parameters of radiation-induced injury were significantly attenuated by an intraperitoneal injection of 2 mg/kg of the highly specific superoxide dismutase mimic, GC4401, 30 min before each fraction. Innovation: Sirtuin 3 (SIRT3) is believed to regulate mitochondrial oxidative metabolism and antioxidant defenses in response to acute radiation-induced liver injury. This work provides strong evidence for the causal role of O2•− in the liver injury process initiated by whole-body irradiation in SIRT3−/− mice. Conclusion: These results support the hypothesis that O2•− mediates acute liver injury in SIRT3−/− animals exposed to whole-body γ-radiation and suggest that GC4401 could be used as a radio-protective compound in vivo. Antioxid. Redox Signal. 20, 1423–1435. PMID:23919724

  10. Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury.

    PubMed

    Wagner, Amy K; McCullough, Emily H; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L; Dobos, Julie A; Brett, Christopher A; Santarsieri, Martina; Dixon, C Edward; Berga, Sarah L; Fabio, Anthony

    2011-06-01

    Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for

  11. Accelerated recovery from acute brain injuries: clinical efficacy of neurotrophic treatment in stroke and traumatic brain injuries.

    PubMed

    Bornstein, N; Poon, W S

    2012-04-01

    Stroke is one of the most devastating vascular diseases in the world as it is responsible for almost five million deaths per year. Almost 90% of all strokes are ischemic and mainly due to atherosclerosis, cardiac embolism and small-vessel disease. Intracerebral or subarachnoid hemorrhage can lead to hemorrhagic stroke, which usually has the poorest prognosis. Cerebrolysin is a peptide preparation which mimics the action of a neurotrophic factor, protecting stroke-injured neurons and promoting neuroplasticity and neurogenesis. Cerebrolysin has been widely studied as a therapeutic tool for both ischemic and hemorrhagic stroke, as well as traumatic brain injury. In ischemic stroke, Cerebrolysin given as an adjuvant therapy to antiplatelet and rheologically active medication resulted in accelerated improvement in global, neurological and motor functions, cognitive performance and activities of daily living. Cerebrolysin was also safe and well tolerated when administered in patients suffering from hemorrhagic stroke. Traumatic brain injury leads to transient or chronic impairments in physical, cognitive, emotional and behavioral functions. This is associated with deficits in the recognition of basic emotions, the capacity to interpret the mental states of others, and executive functioning. Pilot clinical studies with adjuvant Cerebrolysin in the acute and postacute phases of the injury have shown faster recovery, which translates into an earlier onset of rehabilitation and shortened hospitalization time. PMID:22514794

  12. Difficulties in diagnosing acute kidney injury post liver transplantation using serum creatinine based diagnostic criteria

    PubMed Central

    Agarwal, Banwari; Davenport, Andrew

    2014-01-01

    Renal function in patients with advanced cirrhosis is an important prognostic factor for survival both prior to and following liver transplantation. The importance of renal function is reflected by the introduction of the model for end stage liver disease (MELD) score, which includes serum creatinine. The MELD score has been shown to predict the short term risk of death for transplant wait listed patients and is currently used by many countries to allocate liver transplants on the basis of severity of underlying illness. Changes in serum creatinine are also used to stage acute kidney injury. However prior to liver transplantation the serum creatinine typically over estimates underlying renal function, particularly when a colorimetric Jaffe based assay is used, and paradoxically then under estimates renal function post liver transplantation, particularly when immunophyllins are started early as part of transplant immunosuppression. As acute kidney injury is defined by changes in serum creatinine, this potentially leads to over estimation of the incidence and severity of acute kidney injury in the immediate post-operative period. PMID:25349641

  13. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    SciTech Connect

    Yoo, Seong Ho; Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2013-07-05

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.

  14. Yogurt: effect on leukocytes and blood coagulation in an acute liver injury model.

    PubMed

    Haro, Cecilia; Lazarte, Sandra; Zelaya, Hortensia; Alvarez, Susana; Agüero, Graciela

    2009-08-01

    This study determined whether cow or goat yogurt administration has a preventive effect on the hepatic damage undergone during an acute liver injury. Acute liver injury was induced by an intraperitoneal injection of d-galactosamine. Groups of mice were fed with cow or goat yogurt for 2 days or 7 days before the d-galactosamine injection. Blood and liver samples were obtained 12 hours after d-galactosamine inoculation. d-Galactosamine induced an increase in serum amino-transaminases, a reduction in the number of blood leukocytes, an enhancement in neutrophil myeloperoxidase activity, a recruitment of leukocytes toward the liver, an increase in cell death, and an alteration in prothrombin time, activated partial thromboplastin time, and fibrinogen levels. Treatment with cow or goat yogurt was effective at increasing leukocyte number and decrease myeloperoxidase activity. We also observed a decrease in leukocyte accumulation in the liver and a reduction in cell death. Activated partial thromboplastin time and fibrinogen were normalized, but prothrombin time only showed an improvement without reaching normal values. Cow or goat yogurts were effective at protecting against an experimental acute liver injury, especially when administered for 7 days. PMID:19735179

  15. Ventilator-Induced Lung Injury (VILI) in Acute Respiratory Distress Syndrome (ARDS): Volutrauma and Molecular Effects

    PubMed Central

    Carrasco Loza, R; Villamizar Rodríguez, G; Medel Fernández, N

    2015-01-01

    Acute Respiratory Distress Syndrome (ARDS) is a clinical condition secondary to a variety of insults leading to a severe acute respiratory failure and high mortality in critically ill patients. Patients with ARDS generally require mechanical ventilation, which is another important factor that may increase the ALI (acute lung injury) by a series of pathophysiological mechanisms, whose common element is the initial volutrauma in the alveolar units, and forming part of an entity known clinically as ventilator-induced lung injury (VILI). Injured lungs can be partially protected by optimal settings and ventilation modes, using low tidal volume (VT) values and high positive-end expiratory pressure (PEEP). The benefits in ARDS outcomes caused by these interventions have been confirmed by several prospective randomized controlled trials (RCTs) and are attributed to reduction in volutrauma. The purpose of this article is to present an approach to VILI pathophysiology focused on the effects of volutrauma that lead to lung injury and the ‘mechanotransduction’ mechanism. A more complete understanding about the molecular effects that physical forces could have, is essential for a better assessment of existing strategies as well as the development of new therapeutic strategies to reduce the damage resulting from VILI, and thereby contribute to reducing mortality in ARDS. PMID:26312103

  16. Cromolyn ameliorates acute and chronic injury in a rat lung transplant model

    PubMed Central

    Chang, Jui-Chih; Leung, Jason; Tang, Tao; Holzknecht, Zoie E.; Hartwig, Matthew G.; Davis, R. Duane; Parker, William; Abraham, Soman N.; Lin, Shu S.

    2015-01-01

    BACKGROUND Mast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown. METHODS In this study, we evaluated the role of mast cells in pulmonary allograft rejection using an orthotopic rat pulmonary allograft model that utilizes chronic aspiration of gastric fluid to reliably obtain OB. Pulmonary allograft recipients (n = 35) received chronic aspiration of gastric fluid with (n = 10) and without (n = 16) treatment with a mast cell membrane stabilizer, cromolyn sodium, or chronic aspiration with normal saline (n = 9) as a control. RESULTS The acute graft injury associated with long ischemic time in the model (6 hours total ischemic time; typical acute graft injury rate ~30%) was apparently blocked by cromolyn, because peri-operative mortality associated with the acute graft injury was not observed in any of the animals receiving cromolyn (p = 0.045). Further, the rats receiving cromolyn developed significantly fewer OB lesions than those treated with gastric fluid alone (p < 0.001), with a mean reduction of 46% of the airways affected. CONCLUSIONS These findings provide impetus for further studies aimed at elucidating the effects of cromolyn and the role of mast cells in pulmonary allotransplantation. PMID:24768366

  17. Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation.

    PubMed

    Zhang, Weixin; Yin, Lianhong; Tao, Xufeng; Xu, Lina; Zheng, Lingli; Han, Xu; Xu, Youwei; Wang, Changyuan; Peng, Jinyong

    2016-07-01

    In our previous study, the effects of dioscin against alcohol-, carbon tetrachloride- and acetaminophen-induced liver damage have been found. However, the activity of it against dimethylnitrosamine (DMN)-induced acute liver injury remained unknown. In the present study, dioscin markedly decreased serum ALT and AST levels, significantly increased the levels of SOD, GSH-Px, GSH, and decreased the levels of MDA, iNOS and NO. Mechanism study showed that dioscin significantly decreased the expression levels of IL-1β, IL-6, TNF-α, IκBα, p50 and p65 through regulating TLR4/MyD88 pathway to rehabilitate inflammation. In addition, dioscin markedly up-regulated the expression levels of SIRT1, HO-1, NQO1, GST and GCLM through increasing nuclear translocation of Nrf2 against oxidative stress. Furthermore, dioscin significantly decreased the expression levels of FasL, Fas, p53, Bak, Caspase-3/9, and upregulated Bcl-2 level through decreasing IRF9 level against apoptosis. In conclusion, dioscin showed protective effect against DMN-induced acute liver injury via ameliorating apoptosis, oxidative stress and inflammation, which should be developed as a new candidate for the treatment of acute liver injury in the future. PMID:27317992

  18. Acute fibrinous and organising pneumonia: a rare histopathological variant of chemotherapy-induced lung injury.

    PubMed

    Gupta, Arjun; Sen, Shiraj; Naina, Harris

    2016-01-01

    Bleomycin-induced lung injury is the most common chemotherapy-associated lung disease, and is linked with several histopathological patterns. Acute fibrinous and organising pneumonia (AFOP) is a relatively new and rare histological pattern of diffuse lung injury. We report the first known case of bleomycin-induced AFOP. A 36-year-old man with metastatic testicular cancer received three cycles of bleomycin, etoposide and cisplatin, before being transitioned to paclitaxel, ifosfamide and cisplatin. He subsequently presented with exertional dyspnoea, cough and pleuritic chest pain. CT of the chest demonstrated bilateral ground glass opacities with peribronchovascular distribution and pulmonary function tests demonstrated a restrictive pattern of lung disease with impaired diffusion. Transbronchial biopsy revealed intra-alveolar fibrin deposits with organising pneumonia, consisting of intraluminal loose connective tissue consistent with AFOP. The patient received high-dose corticosteroids with symptomatic and radiographic improvement. AFOP should be recognised as a histopathological variant of bleomycin-induced lung injury. PMID:27053543

  19. Acute kidney injury from cherry concentrate in a patient with CKD.

    PubMed

    Luciano, Randy L

    2014-03-01

    Nutraceuticals are supplements and medical foods that offer numerous health benefits. However, these substances may have adverse effects on multiple organ systems, leading to significant morbidity. I present a patient with chronic kidney disease who experienced hemodynamically mediated acute kidney injury and hyperkalemia after daily consumption of cherry concentrate. The method of injury was most likely cyclooxygenase inhibition by the compounds in cherries that mimic the mechanism of action of nonsteroidal anti-inflammatory medications. Ceasing cherry concentrate consumption led to improvements in both the patient's hyperkalemia and kidney injury. Physicians should be aware of the potentially harmful side effects of cherry concentrate and approach the use of cherry extract or concentrate with caution in patients with underlying kidney disease. PMID:24290246

  20. Outcome of the acute glomerular injury in proliferative lupus nephritis

    SciTech Connect

    Chagnac, A.; Kiberd, B.A.; Farinas, M.C.; Strober, S.; Sibley, R.K.; Hoppe, R.; Myers, B.D. )

    1989-09-01

    Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

  1. Neurosensory Symptom Complexes after Acute Mild Traumatic Brain Injury

    PubMed Central

    Szczupak, Mikhaylo; Kiderman, Alexander; Crawford, James; Murphy, Sara; Marshall, Kathryn; Pelusso, Constanza

    2016-01-01

    Mild Traumatic Brain Injury (mTBI) is a prominent public health issue. To date, subjective symptom complaints primarily dictate diagnostic and treatment approaches. As such, the description and qualification of these symptoms in the mTBI patient population is of great value. This manuscript describes the symptoms of mTBI patients as compared to controls in a larger study designed to examine the use of vestibular testing to diagnose mTBI. Five symptom clusters were identified: Post-Traumatic Headache/Migraine, Nausea, Emotional/Affective, Fatigue/Malaise, and Dizziness/Mild Cognitive Impairment. Our analysis indicates that individuals with mTBI have headache, dizziness, and cognitive dysfunction far out of proportion to those without mTBI. In addition, sleep disorders and emotional issues were significantly more common amongst mTBI patients than non-injured individuals. A simple set of questions inquiring about dizziness, headache, and cognitive issues may provide diagnostic accuracy. The consideration of other symptoms may be critical for providing prognostic value and treatment for best short-term outcomes or prevention of long-term complications. PMID:26727256

  2. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1

    PubMed Central

    Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

    2016-01-01

    Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

  3. Endoplasmic reticulum stress-regulated CXCR3 pathway mediates inflammation and neuronal injury in acute glaucoma

    PubMed Central

    Ha, Y; Liu, H; Xu, Z; Yokota, H; Narayanan, S P; Lemtalsi, T; Smith, S B; Caldwell, R W; Caldwell, R B; Zhang, W

    2015-01-01

    Acute glaucoma is a leading cause of irreversible blindness in East Asia. The mechanisms underlying retinal neuronal injury induced by a sudden rise in intraocular pressure (IOP) remain obscure. Here we demonstrate that the activation of CXCL10/CXCR3 axis, which mediates the recruitment and activation of inflammatory cells, has a critical role in a mouse model of acute glaucoma. The mRNA and protein expression levels of CXCL10 and CXCR3 were significantly increased after IOP-induced retinal ischemia. Blockade of the CXCR3 pathway by deleting CXCR3 gene significantly attenuated ischemic injury-induced upregulation of inflammatory molecules (interleukin-1β and E-selectin), inhibited the recruitment of microglia/monocyte to the superficial retina, reduced peroxynitrite formation, and prevented the loss of neurons within the ganglion cell layer. In contrast, intravitreal delivery of CXCL10 increased leukocyte recruitment and retinal cell apoptosis. Inhibition of endoplasmic reticulum (ER) stress with chemical chaperones partially blocked ischemic injury-induced CXCL10 upregulation, whereas induction of ER stress with tunicamycin enhanced CXCL10 expression in retina and primary retinal ganglion cells. Interestingly, deleting CXCR3 attenuated ER stress-induced retinal cell death. In conclusion, these results indicate that ER stress-medicated activation of CXCL10/CXCR3 pathway has an important role in retinal inflammation and neuronal injury after high IOP-induced ischemia. PMID:26448323

  4. Repair of acute injuries of the lateral ligament complex of the ankle by suture anchors

    PubMed Central

    Liu, Xiang-Fei; Fang, Yang; Cao, Zhong-Hua; Li, Guang-Feng; Yang, Guo-Qing

    2015-01-01

    Objective: The objective of this study was to investigate the clinical curative effect of stage I repair of acute injuries of the lateral ligament complex of the ankle by the application of suture anchors. Methods: We retrospectively analyzed 18 cases of III degree acute injuries of the lateral ligament complex of the ankle. Results: There were statistically significant differences in preoperative and last follow-up VAS pain scores and AOFAS ankle hind-foot function scores. The X-ray talus displacement values in the anterior drawer test and pressure anteroposterior X-ray talar tilt in the ankle talar tilt test also showed statistically significant differences. Complications occurred in 2 patients, incision surface infection in one, and postoperative lateral dorsal skin numbness in one. All these cases were cured after symptomatic treatment. At the last follow-up all patients’ ankle joint activity recovered to their preinjury function levels. Conclusion: The application of suture anchors for small incision stage I repair of the lateral collateral ligament of ankle joint degree III injury, can effectively restored the stability of ankle joint, and prevent the occurrence of chronic ankle instability complications. It is effective and feasible for the treatment of ankle joint lateral collateral ligament injuries. PMID:26885144

  5. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1.

    PubMed

    Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

    2016-01-01

    Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

  6. Intraoperative Targeted Temperature Management in Acute Brain and Spinal Cord Injury.

    PubMed

    Kraft, Jacqueline; Karpenko, Anna; Rincon, Fred

    2016-02-01

    Acute brain and spinal cord injuries affect hundreds of thousands of people worldwide. Though advances in pre-hospital and emergency and neurocritical care have improved the survival of some to these devastating diseases, very few clinical trials of potential neuro-protective strategies have produced promising results. Medical therapies such as targeted temperature management (TTM) have been trialed in traumatic brain injury (TBI), spinal cord injury (SCI), acute ischemic stroke (AIS), subarachnoid hemorrhage (SAH), and intracranial hemorrhage (ICH), but in no study has a meaningful effect on outcome been demonstrated. To this end, patient selection for potential neuro-protective therapies such as TTM may be the most important factor to effectively demonstrate efficacy in clinical trials. The use of TTM as a strategy to treat and prevent secondary neuronal damage in the intraoperative setting is an area of ongoing investigation. In this review we will discuss recent and ongoing studies that address the role of TTM in combination with surgical approaches for different types of brain injury. PMID:26759319

  7. Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury

    PubMed Central

    Whitaker, Ryan M.; Stallons, L. Jay; Kneff, Joshua E.; Alge, Joseph L.; Harmon, Jennifer L.; Rahn, Jennifer J.; Arthur, John M.; Beeson, Craig C.; Chan, Sherine L.; Schnellmann, Rick G.

    2015-01-01

    Recent studies show the importance of mitochondrial dysfunction in the initiation and progression of acute kidney injury (AKI). However, no biomarkers exist linking renal injury to mitochondrial function and integrity. To this end, we evaluated urinary mitochondrial DNA (UmtDNA) as a biomarker of renal injury and function in humans with AKI following cardiac surgery. mtDNA was isolated from the urine of patients following cardiac surgery and quantified by qPCR. Patients were stratified into no AKI, stable AKI and progressive AKI groups based on Acute Kidney Injury Network (AKIN) staging. UmtDNA was elevated in progressive AKI patients, and was associated with progression of patients with AKI at collection to higher AKIN stages. To evaluate the relationship of UmtDNA to measures of renal mitochondrial integrity in AKI, mice were subjected to sham surgery or varying degrees of ischemia followed by 24 hours of reperfusion. UmtDNA increased in mice after 10-15 minutes of ischemia and positively correlated with ischemia time. Furthermore, UmtDNA was predictive of AKI in the mouse model. Finally, UmtDNA levels were negatively correlated with renal cortical mtDNA and mitochondrial gene expression. These translational studies demonstrate that UmtDNA is associated with recovery from AKI following cardiac surgery by serving as an indicator of mitochondrial integrity. Thus, UmtDNA may serve as valuable biomarker for the development of mitochondrial targeted therapies in AKI. PMID:26287315

  8. Mouse models and methods for studying human disease, acute kidney injury (AKI).

    PubMed

    Ramesh, Ganesan; Ranganathan, Punithavathi

    2014-01-01

    Acute kidney injury (AKI) is serious complication in hospitalized patients with high level of mortality. There is not much progress made for the past 50 years in reducing the mortality rate despite advances in understanding disease pathology. Using variety of animal models of acute kidney injury, scientist studies the pathogenic mechanism of AKI and to test therapeutic drugs, which may reduce renal injury. Among them, renal pedicle clamping and cisplatin induced nephrotoxicity in mice are most prominently used, mainly due to the availability of gene knockouts to study specific gene functions, inexpensive and availability of the inbred strain with less genetic variability. However, ischemic mouse model is highly variable and require excellent surgical skills to reduce variation in the observation. In this chapter, we describe a detailed protocol of the mouse model of bilateral renal ischemia-reperfusion and cisplatin induced nephrotoxicity. We also discuss the protocol for the isolation and analysis of infiltrated inflammatory cell into the kidney by flow cytometry. Information provided in this chapter will help scientist who wants to start research on AKI and want to establish the mouse model for ischemic and toxic kidney injury. PMID:25064118

  9. Acute hepatic injury with amphotericin B deoxycholate in an immunocompetent patient.

    PubMed

    Wagner, Jamie L; Bell, Allison M

    2016-01-01

    Amphotericin B deoxycholate (AmBd) is rarely used due to its adverse effect profile, which includes nephrotoxicity, infusion-related reactions, and hepatotoxicity. The incidence of hepatotoxicity related to AmBd is 18-23%, but the reports of this adverse effect are mainly in immunocompromised patients receiving chemotherapy. We report a case of AmBd-related acute hepatic injury in an immunocompetent male with multiple medical problems. The patient initially had acute hepatic injury likely caused by poor nutritional status and a diagnosis of failure to thrive, but was recovering. He was also diagnosed with bilateral renal fungal mycetomas and received systemic treatment initially with micafungin and then fluconazole after urine cultures returned with the growth of Candida glabrata. Therapy was expanded to systemic AmBd when the fungal balls persisted. The patient subsequently developed hepatic re-injury with 1 dose of AmBd, and the therapy was discontinued. Caution should be exerted when utilizing AmBd in treating patients with previous hepatic injury. PMID:27440960

  10. Acute hepatic injury with amphotericin B deoxycholate in an immunocompetent patient

    PubMed Central

    Wagner, Jamie L.; Bell, Allison M.

    2016-01-01

    Amphotericin B deoxycholate (AmBd) is rarely used due to its adverse effect profile, which includes nephrotoxicity, infusion-related reactions, and hepatotoxicity. The incidence of hepatotoxicity related to AmBd is 18–23%, but the reports of this adverse effect are mainly in immunocompromised patients receiving chemotherapy. We report a case of AmBd-related acute hepatic injury in an immunocompetent male with multiple medical problems. The patient initially had acute hepatic injury likely caused by poor nutritional status and a diagnosis of failure to thrive, but was recovering. He was also diagnosed with bilateral renal fungal mycetomas and received systemic treatment initially with micafungin and then fluconazole after urine cultures returned with the growth of Candida glabrata. Therapy was expanded to systemic AmBd when the fungal balls persisted. The patient subsequently developed hepatic re-injury with 1 dose of AmBd, and the therapy was discontinued. Caution should be exerted when utilizing AmBd in treating patients with previous hepatic injury.

  11. Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?

    PubMed Central

    2012-01-01

    A growing understanding of the complexity of the pathophysiology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), coupled with advances in stem cell biology, has led to a renewed interest in the therapeutic potential of stem cells for this devastating disease. Mesenchymal stem cells appear closest to clinical translation, given the evidence that they may favourably modulate the immune response to reduce lung injury, while maintaining host immune-competence and also facilitating lung regeneration and repair. The demonstration that human mesenchymal stem cells exert benefit in the endotoxin-injured human lung is particularly persuasive. Endothelial progenitor cells also demonstrate promise in reducing endothelial damage, which is a key pathophysiological feature of ALI. Embryonic and induced pluripotent stem cells are at an earlier stage in the translational process, but offer the hope of directly replacing injured lung tissue. The lung itself also contains endogenous stem cells, which may ultimately offer the greatest hope for lung diseases, given their physiologic role in replacing and regenerating native lung tissues. However, significant deficits remain in our knowledge regarding the mechanisms of action of stem cells, their efficacy in relevant pre-clinical models, and their safety, particularly in critically ill patients. These gaps need to be addressed before the enormous therapeutic potential of stem cells for ALI/ARDS can be realised. PMID:22424108

  12. Adenoviral augmentation of elafin protects the lung against acute injury mediated by activated neutrophils and bacterial infection.

    PubMed

    Simpson, A J; Wallace, W A; Marsden, M E; Govan, J R; Porteous, D J; Haslett, C; Sallenave, J M

    2001-08-01

    During acute pulmonary infection, tissue injury may be secondary to the effects of bacterial products or to the effects of the host inflammatory response. An attractive strategy for tissue protection in this setting would combine antimicrobial activity with inhibition of human neutrophil elastase (HNE), a key effector of neutrophil-mediated tissue injury. We postulated that genetic augmentation of elafin (an endogenous inhibitor of HNE with intrinsic antimicrobial activity) could protect the lung against acute inflammatory injury without detriment to host defense. A replication-deficient adenovirus encoding elafin cDNA significantly protected A549 cells against the injurious effects of both HNE and whole activated human neutrophils in vitro. Intratracheal replication-deficient adenovirus encoding elafin cDNA significantly protected murine lungs against injury mediated by Pseudomonas aeruginosa in vivo. Genetic augmentation of elafin therefore has the capacity to protect the lung against the injurious effects of both bacterial pathogens resistant to conventional antibiotics and activated neutrophils. PMID:11466403

  13. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke

    PubMed Central

    Khanna, Savita; Heigel, Mallory; Weist, Jessica; Gnyawali, Surya; Teplitsky, Seth; Roy, Sashwati; Sen, Chandan K.; Rink, Cameron

    2015-01-01

    The vitamin E family includes both tocopherols and tocotrienols, where α-tocopherol (αTOC) is the most bioavailable form. Clinical trials testing the therapeutic efficacy of high-dose αTOC against stroke have largely failed or reported negative outcomes when a “more is better” approach to supplementation (>400 IU/d) was used. This work addresses mechanisms by which supraphysiologic αTOC may contribute to stroke-induced brain injury. Ischemic stroke injury and the neuroinflammatory response were studied in tocopherol transfer protein-deficient mice maintained on a diet containing αTOC vitamin E at the equivalent human dose of 1680 IU/d. Ischemic stroke-induced brain injury was exacerbated in the presence of supraphysiologic brain αTOC levels. At 48 h after stroke, S100B and RAGE expression was increased in stroke-affected cortex of mice with elevated brain αTOC levels. Such increases were concomitant with aggravated microglial activation and neuroinflammatory signaling. A poststroke increase in markers of oxidative injury and neurodegeneration in the presence of elevated brain αTOC establish that at supraphysiologic levels, αTOC potentiates neuroinflammatory responses to acute ischemic stroke. Exacerbation of microglial activation by excessive αTOC likely depends on its unique cell signaling regulatory properties independent of antioxidant function. Against the background of clinical failure for high-dose αTOC, outcomes of this work identify risk for exacerbating stroke-induced brain injury as a result of supplementing diet with excessive levels of αTOC.—Khanna, S., Heigel,M., Weist, J., Gnyawali, S., Teplitsky, S., Roy, S., Sen, C. K., Rink, C. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke. PMID:25411436

  14. Pyridoxamine reduces postinjury fibrosis and improves functional recovery after acute kidney injury.

    PubMed

    Skrypnyk, Nataliya I; Voziyan, Paul; Yang, Haichun; de Caestecker, Christian R; Theberge, Marie-Claude; Drouin, Mathieu; Hudson, Billy; Harris, Raymond C; de Caestecker, Mark P

    2016-08-01

    Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose-dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long-term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI. PMID:27194713

  15. Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

    PubMed

    Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

    2016-01-01

    The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. PMID:26319781

  16. Single-leg drop landing motor control strategies following acute ankle sprain injury.

    PubMed

    Doherty, C; Bleakley, C; Hertel, J; Caulfield, B; Ryan, J; Delahunt, E

    2015-08-01

    No research currently exists investigating the effect of acute injury on single-limb landing strategies. The aim of the current study was to analyze the coordination strategies of participants in the acute phase of lateral ankle sprain (LAS) injury. Thirty-seven participants with acute, first-time LAS and 19 uninjured participants completed a single-leg drop landing task on both limbs. Three-dimensional kinematic (angular displacement) and sagittal plane kinetic (moment-of-force) data were acquired for the joints of the lower extremity from 200 ms pre-initial contact (IC) to 200 ms post-IC. The peak magnitude of the vertical component of the ground reaction force (GRF) was also computed. Injured participants displayed a bilateral increase in hip flexion, with altered transverse plane kinematic profiles at the knee and ankle for both limbs (P < 0.05). This coincided with a reduction in the net-supporting flexor moment of the lower extremity (P < 0.05) and magnitude of the peak vertical GRF for the injured limb (21.82 ± 2.44 N/kg vs 24.09 ± 2.77 N/kg; P = 0.013) in injured participants compared to control participants. These results demonstrate that compensatory movement strategies are utilized by participants with acute LAS to successfully reduce the impact forces of landing. PMID:24975875

  17. Acupuncture Treatment for Acute Ankle Injury in the Emergency Department: A Preliminary Case Report.

    PubMed

    Tantivesruangdet, Nopmanee

    2016-02-01

    Acupuncture is an ancient medical treatment that is increasingly attracting the interest of the public. It is a complementary therapy that is widely used for management of pain, especially chronic discomfort caused by migraine, low-back pain and osteoarthritis of the knee(¹⁻³). The evidence base for the effectiveness of acupuncture and its clinical applications is controversial, and although its efficacy and safety in the management of acute pain have been demonstrated, the quality of this modality is still questionable. The present study reports a case of acute ankle injury, which was treated with acupuncture. A 33-year-old man presented with acute twisted ankle injury. He had pain with swelling around the ankle, and he was experiencing difficulty in walking. His clinical diagnosis was acute ankle sprain with severe pain. Several drug treatments are used for pain control, but in this case, we used acupuncture. After treatment, his pain diminished significantly with a decrease in VAS pain level from 8 to 4 in 20 minutes. At follow-up after one month, we found no skin infection in this case. PMID:27266242

  18. Involvement of TGF-β1/Smad3 Signaling in Carbon Tetrachloride-Induced Acute Liver Injury in Mice

    PubMed Central

    Niu, Liman; Cui, Xueling; Qi, Yan; Xie, Dongxue; Wu, Qian; Chen, Xinxin; Ge, Jingyan; Liu, Zhonghui

    2016-01-01

    Transforming growth factor-beta1 (TGF-β1) is a major factor in pathogenesis of chronic hepatic injury. Carbon tetrachloride (CCl4) is a liver toxicant, and CCl4-induced liver injury in mouse is a classical animal model of chemical liver injury. However, it is still unclear whether TGF-β1 is involved in the process of CCl4-induced acute chemical liver injury. The present study aimed to evaluate the role of TGF-β1 and its signaling molecule Smad3 in the acute liver injury induce by CCl4. The results showed that CCl4 induced acute liver injury in mice effectively confirmed by H&E staining of liver tissues, and levels of not only liver injury markers serum ALT and AST, but also serum TGF-β1 were elevated significantly in CCl4-treated mice, compared with the control mice treated with olive oil. Our data further revealed that TGF-β1 levels in hepatic tissue homogenate increased significantly, and type II receptor of TGF-β (TβRII) and signaling molecules Smad2, 3, mRNA expressions and Smad3 and phospho-Smad3 protein levels also increased obviously in livers of CCl4-treated mice. To clarify the effect of the elevated TGF-β1/Smad3 signaling on CCl4-induced acute liver injury, Smad3 in mouse liver was overexpressed in vivo by tail vein injection of Smad3-expressing plasmids. Upon CCl4 treatment, Smad3-overexpressing mice showed more severe liver injury identified by H&E staining of liver tissues and higher serum ALT and AST levels. Simultaneously, we found that Smad3-overexpressing mice treated with CCl4 showed more macrophages and neutrophils infiltration in liver and inflammatory cytokines IL-1β and IL-6 levels increment in serum when compared with those in control mice treated with CCl4. Moreover, the results showed that the apoptosis of hepatocytes increased significantly, and apoptosis-associated proteins Bax, cytochrome C and the cleaved caspase 3 expressions were up-regulated in CCl4-treated Smad3-overexpressing mice as well. These results suggested that TGF

  19. Salivary biochemical markers as potential acute toxicity parameters for acute radiation injury: A study on small experimental animals.

    PubMed

    Soni, S; Agrawal, P; Kumar, N; Mittal, G; Nishad, D K; Chaudhury, N K; Bhatnagar, A; Basu, M; Chhillar, N

    2016-03-01

    Researchers have been evaluating several biodosimetric/screening approaches to assess acute radiation injury, related to mass causality. Keeping in mind this background, we hypothesized that effect of whole-body irradiation in single fraction in graded doses can affect the secretion of various salivary components that could be used as acute radiation injury/toxicity marker, which can be used in screening of large population at the time of nuclear accidents/disaster. Thirty Sprague Dawley rats treated with whole-body cobalt-60 gamma irradiation of dose 1-5 Gy (dose rate: 0.95 Gy/min) were included in this study. Whole mixed saliva was collected from all animals before and after radiation up to 72 h postradiation. Saliva was analyzed for electrolytes, total protein, urea, and amylase. Intragroup comparison of salivary parameters at different radiation doses showed significant differences. Potassium was significantly increased as the dose increased from 1 Gy to 5 Gy (p < 0.01) with effect size of difference (r > 0.5). Sodium was significantly altered after 3-5 Gy (p < 0.01, r > 0.5), except 1 and 2 Gy, whereas changes in sodium level were nonsignificant (p > 0.5). Urea, total protein, and amylase levels were also significantly increased as the radiation dose increased (p < 0.01) with large effect size of difference (r > 0.5). This study suggests that salivary parameters were sensitive toward radiation even at low radiation dose which can be used as a predictor of radiation injury. PMID:25813962

  20. Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome

    PubMed Central

    Hagawane, T.N.; Gaikwad, R.V.; Kshirsagar, N.A.

    2016-01-01

    Background & objectives: Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS. Methods: Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest X-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done. Results: It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. Interpretation & conclusions: The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury. PMID

  1. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period

    PubMed Central

    Wylie, Glenn R.; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R.

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject’s reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  2. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period.

    PubMed

    Wylie, Glenn R; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject's reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  3. The multifaceted role of the renal microvasculature during acute kidney injury.

    PubMed

    Maringer, Katherine; Sims-Lucas, Sunder

    2016-08-01

    Pediatric acute kidney injury (AKI) represents a complex disease process for clinicians as it is multifactorial in cause and only limited treatment or preventatives are available. The renal microvasculature has recently been implicated in AKI as a strong therapeutic candidate involved in both injury and recovery. Significant progress has been made in the ability to study the renal microvasculature following ischemic AKI and its role in repair. Advances have also been made in elucidating cell-cell interactions and the molecular mechanisms involved in these interactions. The ability of the kidney to repair post AKI is closely linked to alterations in hypoxia, and these studies are elucidated in this review. Injury to the microvasculature following AKI plays an integral role in mediating the inflammatory response, thereby complicating potential therapeutics. However, recent work with experimental animal models suggests that the endothelium and its cellular and molecular interactions are attractive targets to prevent injury or hasten repair following AKI. Here, we review the cellular and molecular mechanisms of the renal endothelium in AKI, as well as repair and recovery, and potential therapeutics to prevent or ameliorate injury and hasten repair. PMID:26493067

  4. Mast Cells Mediate Acute Kidney Injury through the Production of TNF

    PubMed Central

    Summers, Shaun A.; Chan, Jacky; Gan, Poh-Yi; Dewage, Lakshi; Nozaki, Yuji; Steinmetz, Oliver M.; Nikolic-Paterson, David J.; Kitching, A. Richard

    2011-01-01

    Leukocyte recruitment contributes to acute kidney injury (AKI), but the mechanisms by which leukocytes promote injury are not completely understood. The degranulation of mast cells releases inflammatory molecules, including TNF, but whether these cells participate in the pathogenesis of AKI is unknown. Here, we induced AKI with cisplatin in mast cell-deficient and wild-type mice. Compared with wild-type mice, deficiency of mast cells attenuated renal injury, reduced serum levels of TNF, and reduced recruitment of leukocytes to the inflamed kidney. Mast cell-deficient mice also exhibited significantly lower intrarenal expression of leukocyte chemoattractants. Mast cell-deficient mice reconstituted with mast cells from wild-type mice exhibited similar cisplastin-induced renal damage and serum levels of TNF as wild-type mice. In contrast, mast cell-deficient mice reconstituted with mast cells from TNF-deficient mice continued to demonstrate significant attenuation of cisplatin-induced renal injury. Furthermore, the mast-cell stabilizer sodium chromoglycate also significantly abrogated renal injury in this model of AKI. Taken together, these results suggest that mast cells mediate AKI through the production of TNF. PMID:22021718

  5. Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury

    PubMed Central

    Junk, Anna K.; Mammis, Antonios; Savitz, Sean I.; Singh, Manjeet; Roth, Steven; Malhotra, Samit; Rosenbaum, Pearl S.; Cerami, Anthony; Brines, Michael; Rosenbaum, Daniel M.

    2002-01-01

    Erythropoietin (EPO) plays an important role in the brain's response to neuronal injury. Systemic administration of recombinant human EPO (rhEPO) protects neurons from injury after middle cerebral artery occlusion, traumatic brain injury, neuroinflammation, and excitotoxicity. Protection is in part mediated by antiapoptotic mechanisms. We conducted parallel studies of rhEPO in a model of transient global retinal ischemia induced by raising intraocular pressure, which is a clinically relevant model for retinal diseases. We observed abundant expression of EPO receptor (EPO-R) throughout the ischemic retina. Neutralization of endogenous EPO with soluble EPO-R exacerbated ischemic injury, which supports a crucial role for an endogenous EPO/EPO-R system in the survival and recovery of neurons after an ischemic insult. Systemic administration of rhEPO before or immediately after retinal ischemia not only reduced histopathological damage but also promoted functional recovery as assessed by electroretinography. Exogenous EPO also significantly diminished terminal deoxynucleotidyltransferase-mediated dUTP end labeling labeling of neurons in the ischemic retina, implying an antiapoptotic mechanism of action. These results further establish EPO as a neuroprotective agent in acute neuronal ischemic injury. PMID:12130665

  6. Traumatic Brain Injury in Young Children: Post-Acute Effects on Cognitive and School Readiness Skills

    PubMed Central

    Taylor, H. Gerry; Swartwout, Maegan; Yeates, Keith O.; Walz, Nicolay C.; Stancin, Terry; Wade, Shari L.

    2009-01-01

    Previous studies have documented weaknesses in cognitive ability and early academic readiness in young children with traumatic brain injury (TBI). However, few of these studies have rigorously controlled for demographic characteristics, examined the effects of TBI severity on a wide range of skills, or explored moderating influences of environmental factors on outcomes. To meet these objectives, each of three groups of children with TBI (20 with severe, 64 with moderate, and 15 with mild) were compared with a group of 117 children with orthopedic injuries (OI group). The children were hospitalized for their injuries between 3 and 6 years of age and were assessed an average of 1½ months post injury. Analysis revealed generalized weaknesses in cognitive and school readiness skills in the severe TBI group and suggested less pervasive effects of moderate and mild TBI. Indices of TBI severity predicted outcomes within the TBI sample and environmental factors moderated the effects of TBI on some measures. The findings document adverse effects of TBI in early childhood on post-acute cognitive and school readiness skills and indicate that residual deficits are related to both injury severity and the family environment. PMID:18764969

  7. CAF1-knockout mice are more susceptive to lipopolysaccharide-induced acute lung injury

    PubMed Central

    Shi, Jia-Xin; Li, Jia-Shu; Hu, Rong; Li, Xiao-Min; Wang, Hong

    2016-01-01

    The carbon catabolite repressor protein 4 (CCR4)–negative on TATA (NOT) complex includes multiple subunits and is conserved in the eukaryotic cells. The CCR4–NOT complex can regulate gene expression at different levels. Two subunits of the CCR4–NOT complex, CCR4 and CCR4-associated factor 1 (CAF1), possess deadenylase activity. In yeast, the deadenylase activity is mainly provided by the CCR4 subunit; however, the deadenylase activity is provided by both CCR4 and CAF1 in other eukaryotes. A previous study reported that CAF1 but not CCR4 is required for the decay of a reporter mRNA with AU-rich elements. Our previous study showed that CAF1 is involved in the regulation of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) expression. Both ICAM-1 and IL-8 play crucial roles in acute lung injury. In the present study, we examined the effects of CAF1 deficiency on IL-8 and ICAM-1 expression and acute lung injury in mice. Here we showed that there were no differences between the wild-type and CAF1-knockout mice on phenotypes. The lung histology and protein and mRNA levels of IL-8 and ICAM-1 in unstimulated wild-type mice were comparable to those in unstimulated CAF1-knockout mice. However, lipopolysaccharide stimulation led to more severe lung histological injury and greatly higher IL-8 and ICAM-1 expression in CAF1-knockout mice compared to the wild-type mice. These results, together with our previous study, suggest that CAF1 is involved in the regulation of lipopolysaccharide-stimulated IL-8 and ICAM-1 expression in vivo and affects the progression of acute lung injury. PMID:27358572

  8. Modeling the dynamics of recruitment and derecruitment in mice with acute lung injury.

    PubMed

    Massa, Christopher B; Allen, Gilman B; Bates, Jason H T

    2008-12-01

    Lung recruitment and derecruitment contribute significantly to variations in the elastance of the respiratory system during mechanical ventilation. However, the decreases in elastance that occur with deep inflation are transient, especially in acute lung injury. Bates and Irvin (8) proposed a model of the lung that recreates time-varying changes in elastance as a result of progressive recruitment and derecruitment of lung units. The model is characterized by distributions of critical opening and closing pressures throughout the lung and by distributions of speeds with which the processes of opening and closing take place once the critical pressures have been achieved. In the present study, we adapted this model to represent a mechanically ventilated mouse. We fit the model to data collected in a previous study from control mice and mice in various stages of acid-induced acute lung injury (3). Excellent fits to the data were obtained when the normally distributed critical opening pressures were about 5 cmH(2)O above the closing pressures and when the hyperbolically distributed opening velocities were about an order of magnitude greater than the closing velocities. We also found that, compared with controls, the injured mice had markedly increased opening and closing pressures but no change in the velocities, suggesting that the key biophysical change wrought by acid injury is dysfunction of surface tension at the air-liquid interface. Our computational model of lung recruitment and derecruitment dynamics is thus capable of accurately mimicking data from mice with acute lung injury and may provide insight into the altered biophysics of the injured lung. PMID:18948446

  9. Tonsil-derived mesenchymal stem cells alleviate concanavalin A-induced acute liver injury.

    PubMed

    Ryu, Kyung-Ha; Kim, So-Yeon; Kim, Ye-Ryung; Woo, So-Youn; Sung, Sun Hee; Kim, Han Su; Jung, Sung-Chul; Jo, Inho; Park, Joo-Won

    2014-08-01

    Acute liver failure, the fatal deterioration of liver function, is the most common indication for emergency liver transplantation, and drug-induced liver injury and viral hepatitis are frequent in young adults. Stem cell therapy has come into the limelight as a potential therapeutic approach for various diseases, including liver failure and cirrhosis. In this study, we investigated therapeutic effects of tonsil-derived mesenchymal stem cells (T-MSCs) in concanavalin A (ConA)- and acetaminophen-induced acute liver injury. ConA-induced hepatitis resembles viral and immune-mediated hepatic injury, and acetaminophen overdose is the most frequent cause of acute liver failure in the United States and Europe. Intravenous administration of T-MSCs significantly reduced ConA-induced hepatic toxicity, but not acetaminophen-induced liver injury, affirming the immunoregulatory capacity of T-MSCs. T-MSCs were successfully recruited to damaged liver and suppressed inflammatory cytokine secretion. T-MSCs expressed high levels of galectin-1 and -3, and galectin-1 knockdown which partially diminished interleukin-2 and tumor necrosis factor α secretion from cultured T-cells. Galectin-1 knockdown in T-MSCs also reversed the protective effect of T-MSCs on ConA-induced hepatitis. These results suggest that galectin-1 plays an important role in immunoregulation of T-MSCs, which contributes to their protective effect in immune-mediated hepatitis. Further, suppression of T-cell activation by frozen and thawed T-MSCs implies great potential of T-MSC banking for clinical utilization in immune-mediated disease. PMID:24954408

  10. State of the art management of transfusion-related acute lung injury (TRALI).

    PubMed

    Goldberg, Andrew D; Kor, Daryl J

    2012-01-01

    Transfusion-Related Acute Lung Injury (TRALI) is the leading cause of transfusion-related mortality in most developed countries. Despite this fact, well-designed investigations on specific management strategies for TRALI are lacking. Indeed, current recommendations are primarily based on data extrapolated from trials of the histo-pathologically similar Acute Lung Injury and Acute Respiratory Distress Syndromes. The cornerstone of TRALI management is supportive care with oxygen supplementation and ventilatory assistance when needed. When mechanical ventilation is required, attenuating additional ventilator-induced lung injury through the avoidance of high tidal volumes and elevated airway pressures, with additional measures such as positive end-expiratory pressure to prevent low-volume shear stress injury, are recommended. The literature is not currently sufficient to support either corticosteroids or statins as effective therapies in TRALI. Conservative fluid practices are desirable, provided care is taken to avoid hypotension. Preventative strategies have shown the most promise in mitigating this transfusion-related pulmonary complication. Specifically, conservative transfusion practices and deferral of high-plasma component donors who have, or at high risk of having, anti-human leukocyte antigen and/or anti-human neutrophil antigen antibodies have meaningfully impacted the incidence of TRALI. Future considerations for patients who are at increased risk for developing TRALI may include therapies such as anti-platelet agents and alternatives to traditional blood components such as prothrombin complex concentrates (PCC). However, these potential TRALI prevention strategies are insufficiently studied, have unclear risk/benefit profiles and cannot be currently recommended. PMID:22621274

  11. Application of new acute kidney injury biomarkers in human randomized controlled trials.

    PubMed

    Parikh, Chirag R; Moledina, Dennis G; Coca, Steven G; Thiessen-Philbrook, Heather R; Garg, Amit X

    2016-06-01

    The use of novel biomarkers of acute kidney injury (AKI) in clinical trials may help evaluate treatments for AKI. Here we explore potential applications of biomarkers in simulated clinical trials of AKI using data from the TRIBE-AKI multicenter, prospective cohort study of patients undergoing cardiac surgery. First, in a hypothetical trial of an effective therapy at the time of acute tubular necrosis to prevent kidney injury progression, use of an indirect kidney injury marker such as creatinine compared to a new direct biomarker of kidney injury reduces the proportion of true acute tubular necrosis cases enrolled. The result is a lower observed relative risk reduction with the therapy, and lower statistical power to detect a therapy effect at a given sample size. Second, the addition of AKI biomarkers (interleukin-18 and NGAL) to clinical risk factors as eligibility criteria for trial enrollment in early AKI has the potential to increase the proportion of patients who will experience AKI progression and reduce trial cost. Third, we examine AKI biomarkers as outcome measures for the purposes of identifying therapies that warrant further testing in larger, multicenter, multi-country trials. In the hypothetical trial of lower cardiopulmonary bypass time to reduce the risk of postoperative AKI, the sample size required to detect a reduction in AKI is lower if new biomarkers are used to define AKI rather than serum creatinine. Thus, incorporation of new biomarkers of AKI has the potential to increase statistical power, decrease the sample size, and lower the cost of AKI trials. PMID:27165835

  12. αKlotho deficiency in acute kidney injury contributes to lung damage.

    PubMed

    Ravikumar, Priya; Li, Liping; Ye, Jianfeng; Shi, Mingjun; Taniguchi, Masatomo; Zhang, Jianning; Kuro-O, Makoto; Hu, Ming Chang; Moe, Orson W; Hsia, Connie C W

    2016-04-01

    αKlotho is a circulating protein that originates predominantly from the kidney and exerts cytoprotective effects in distant sites. We previously showed in rodents that the lung is particularly vulnerable to αKlotho deficiency. Because acute lung injury is a common and serious complication of acute kidney injury (AKI), we hypothesized that αKlotho deficiency in AKI contributes to lung injury. To test the hypothesis, we created AKI by renal artery ischemia-reperfusion in rats and observed the development of alveolar interstitial edema and increased pulmonary oxidative damage to DNA, protein, and lipids. Administration of αKlotho-containing conditioned media 6 h post-AKI did not alter plasma creatinine but improved recovery of endogenous αKlotho production 3 days post-AKI, reduced lung edema and oxidative damage, and increased endogenous antioxidative capacity in the lung. Intravenously injected αKlotho rapidly exits alveolar capillaries as a macromolecule, suggesting transcytosis and direct access to the epithelium. To explore the epithelial action of αKlotho, we simulated oxidative stress in vitro by adding hydrogen peroxide to cultured A549 lung epithelial cells. Purified recombinant αKlotho directly protected cells at 20 pM with half-maximal effects at 40-50 pM, which is compatible with circulating αKlotho levels. Addition of recombinant αKlotho activated an antioxidant response element reporter and increased the levels of target proteins of the nuclear factor erythroid-derived 2 related factor system. In summary, αKlotho deficiency in AKI contributes to acute lung injury by reducing endogenous antioxidative capacity and increasing oxidative damage in the lung. αKlotho replacement partially reversed these abnormalities and mitigated pulmonary complications in AKI. PMID:26718784

  13. Relationship Between Depressive State and Treatment Characteristics of Acute Cervical Spinal Cord Injury in Japan

    PubMed Central

    Matsuda, Yasufumi; Kubo, Tatsuhiko; Fujino, Yoshihisa; Matsuda, Shinya; Wada, Futoshi; Sugita, Atsuko

    2016-01-01

    Background Few studies have assessed whether treatment of acute cervical spinal cord injury (SCI) patients contributes to depression. Methods Using an administrative database, we assessed patients for whom the diagnosis was unspecified injuries of cervical spinal cord (International Classification of Diseases and Injuries-10th (ICD-10) code; S14.1). We categorized patients with codes for depressive episode (ICD-10 code; F32) or recurrent depressive disorder (F33), or those prescribed antidepressants (tricyclic, tetracyclic, Selective Serotonin Reuptake Inhibitors, Serotonin Noradrenaline Reuptake Inhibitors, Trazodone, Sulpiride, or Mirtazapine) as having a depressive state. We compared the rate of each acute treatment between the depressive state group and the non-depressive state group using chi-square tests, and a multiple logistic regression model was used to identify the association between the acute treatment and depressive state. Results There were 151 patients who were judged to be in a depressive state, and the other 2115 patients were categorized into the non-depressive state group. Intervention of intravenous anesthesia, tracheostomy, artificial respiration, and gastrostomy had a significant positive correlation with depressive state. Multiple logistic regression analysis showed that tracheostomy (odds ratio [OR] 2.18; 95% confidence interval [CI], 1.09–4.38) and artificial respiration (OR 2.28; 95% CI, 1.32–3.93) were significantly associated with depressive state, and men had a 36% reduction in the risk of depressive state compared with women (OR 0.64; 95% CI, 0.44–0.94), whereas age, wound-treatment, all of the orthopedic procedures, intravenous anesthesia, and gastrostomy were not associated with depressive state. Conclusions These findings suggest that tracheostomy, artificial respiration and female gender in the acute phase after cervical SCI might be associated with the development of depression. PMID:26567604

  14. Hepatoprotectant Ursodeoxycholyl Lysophosphatidylethanolamide Increasing Phosphatidylcholine Levels as a Potential Therapy of Acute Liver Injury

    PubMed Central

    Chamulitrat, Walee; Zhang, Wujuan; Xu, Weihong; Pathil, Anita; Setchell, Kenneth; Stremmel, Wolfgang

    2012-01-01

    It has been long known that hepatic synthesis of phosphatidylcholine (PC) is depressed during acute such as carbon tetrachloride-induced liver injury. Anti-hepatotoxic properties of PC as liposomes have been recognized for treatment of acute liver damage. Ursodeoxycholate (UDCA) is a known hepatoprotectant in stabilizing cellular membrane. For therapeutic management of liver injury, we coupled UDCA with a phospholipid known as ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE). UDCA-LPE has been shown to first-in-class hepatoprotectant being superior to UDCA or PC. It inhibits mitochondrial damage and apoptosis, elicits survival signaling pathway, and promotes regeneration of hepatocytes. We herein report that a unique contribution of UDCA-LPE in increasing concentrations of PC in vitro and in vivo. UDCA-LPE-treated hepatocytes contained significantly increased PC levels. UDCA-LPE underwent the hydrolysis to LPE which was not the precursor of the increased PC. The levels of PC in the liver and blood were increased rapidly after intraperitoneally administration UDCA-LPE, and were found to be sustained even after 24 h. Among PC synthesis genes tested, UDCA-LPE treatment of mouse hepatocytes increased transcription of CDP-diacylglycerol synthase 1 which is an enzyme catalyzing phosphatidic acid to generate intermediates for PC synthesis. Thus, UDCA-LPE as a hepatoprotectant was able to induce synthesis of protective PC which would supplement for the loss of PC occurring during acute liver injury. This property has placed UDCA-LPE as a candidate agent for therapy of acute hepatotoxicity such as acetaminophen poisoning. PMID:22363296

  15. Investigation of nanostructural changes following acute injury using atomic force microscopy in rabbit vocal folds.

    PubMed

    Lee, Young Chan; Kim, Ho Jung; Kim, Kyung Sook; Choi, Samjin; Kim, Sung Wan; Park, Hun-Kuk; Eun, Young Gyu

    2015-07-01

    There continues to be a paucity of data regarding the nanostructural changes of vocal fold (VF) collagen after injury. The aim of this study is to investigate the nanostructural and morphological changes in the rabbit VF lamina propria following acute injury using atomic force microscopy (AFM). Unilateral VF injury was performed on 9 New Zealand breeder rabbits. Sacrifice and laryngeal harvest were performed at three time points: 1 day, 3 days, and 7 days after injury. Histology and immunohistochemistry data were collected to confirm extracellular matrix (ECM) changes in rabbit VF. The progressive changes in thickness and D-spacing of VF collagen fibrils were investigated over a 7-day postinjury period using AFM. At post-injury day 1, a fibrin clot and inflammatory cell infiltration were observed at the injured VF. The inflammatory score at postinjury day 1 was highest in injured VF tissue, with a significant decrease at postinjury day 7. The immunoreactivity of inflammatory proteins (COX-2, TNF-α) was observed in VF up to day 7 after injury. AFM investigation showed clustered and disorganized collagen fibrils at the nanoscale resolution at post-injury day 7. Collagen fibrils in injured VF at postinjury day 7 were significantly thicker than control and postinjury days 1 and 3 (P < 0.001). D-spacing of collagen at postinjury day 7 was not studied due to loss of distinct edges resulting from immature collagen deposition. AFM investigation of VF could add valuable information to understanding micromechanical changes in VF scar tissue. PMID:25900427

  16. Pulmonary natural killer T cells play an essential role in mediating hyperoxic acute lung injury.

    PubMed

    Nowak-Machen, Martina; Schmelzle, Moritz; Hanidziar, Dusan; Junger, Wolfgang; Exley, Mark; Otterbein, Leo; Wu, Yan; Csizmadia, Eva; Doherty, Glen; Sitkovsky, Michail; Robson, Simon C

    2013-05-01

    Critically ill patients are routinely exposed to high concentrations of supplemental oxygen for prolonged periods of time, which can be life-saving in the short term, but such exposure also causes severe lung injury and increases mortality. To address this therapeutic dilemma, we studied the mechanisms of the tissue-damaging effects of oxygen in mice. We show that pulmonary invariant natural killer T (iNKT) cells are unexpectedly crucial in the development of acute oxygen-induced lung injury. iNKT cells express high concentrations of the ectonucleotidase CD39, which regulates their state of activation. Both iNKT cell-deficient (Jα18(-/-)) and CD39-null mice tolerate hyperoxia, compared with wild-type control mice that exhibit severe lung injury. An adoptive transfer of wild-type iNKT cells into Jα18(-/-) mice results in hyperoxic lung injury, whereas the transfer of CD39-null iNKT cells does not. Pulmonary iNKT cell activation and proliferation are modulated by ATP-dependent purinergic signaling responses. Hyperoxic lung injury can be induced by selective P2X7-receptor blockade in CD39-null mice. Our data indicate that iNKT cells are involved in the pathogenesis of hyperoxic lung injury, and that tissue protection can be mediated through ATP-induced P2X7 receptor signaling, resulting in iNKT cell death. In conclusion, our data suggest that iNKT cells and purinergic signaling should be evaluated as potential novel therapeutic targets to prevent hyperoxic lung injury. PMID:23349052

  17. Risk taking in hospitalized patients with acute and severe traumatic brain injury.

    PubMed

    Fecteau, Shirley; Levasseur-Moreau, Jean; García-Molina, Alberto; Kumru, Hatiche; Vergara, Raúl Pelayo; Bernabeu, Monste; Roig, Teresa; Pascual-Leone, Alvaro; Tormos, José Maria

    2013-01-01

    Rehabilitation can improve cognitive deficits observed in patients with traumatic brain injury (TBI). However, despite rehabilitation, the ability of making a choice often remains impaired. Risk taking is a daily activity involving numerous cognitive processes subserved by a complex neural network. In this work we investigated risk taking using the Balloon Analogue Risk Task (BART) in patients with acute TBI and healthy controls. We hypothesized that individuals with TBI will take less risk at the BART as compared to healthy individuals. We also predicted that within the TBI group factors such as the number of days since the injury, severity of the injury, and sites of the lesion will play a role in risk taking as assessed with the BART. Main findings revealed that participants with TBI displayed abnormally cautious risk taking at the BART as compared to healthy subjects. Moreover, healthy individuals showed increased risk taking throughout the task which is in line with previous work. However, individuals with TBI did not show this increased risk taking during the task. We also investigated the influence of three patients' characteristics on their performance at the BART: Number of days post injury, Severity of the head injury, and Status of the frontal lobe. Results indicate that performance at the BART was influenced by the number of days post injury and the status of the frontal lobe, but not by the severity of the head injury. Reported findings are encouraging for risk taking seems to naturally improve with time postinjury. They support the need of conducting longitudinal prospective studies to ultimately identify impaired and intact cognitive skills that should be trained postinjury. PMID:24386232

  18. Genome-wide association mapping of acute lung injury in neonatal inbred mice

    PubMed Central

    Nichols, Jennifer L.; Gladwell, Wesley; Verhein, Kirsten C.; Cho, Hye-Youn; Wess, Jürgen; Suzuki, Oscar; Wiltshire, Tim; Kleeberger, Steven R.

    2014-01-01

    Reactive oxygen species (ROS) contribute to the pathogenesis of many acute and chronic pulmonary disorders, including bronchopulmonary dysplasia (BPD), a respiratory condition that affects preterm infants. However, the mechanisms of susceptibility to oxidant stress in neonatal lungs are not completely understood. We evaluated the role of genetic background in response to oxidant stress in the neonatal lung by exposing mice from 36 inbred strains to hyperoxia (95% O2) for 72 h after birth. Hyperoxia-induced lung injury was evaluated by using bronchoalveolar lavage fluid (BALF) analysis and pathology. Statistically significant interstrain variation was found for BALF inflammatory cells and protein (heritability estimates range: 33.6–55.7%). Genome-wide association mapping using injury phenotypes identified quantitative trait loci (QTLs) on chromosomes 1, 2, 4, 6, and 7. Comparative mapping of the chromosome 6 QTLs identified Chrm2 (cholinergic receptor, muscarinic 2, cardiac) as a candidate susceptibility gene, and mouse strains with a nonsynonymous coding single-nucleotide polymorphism (SNP) in Chrm2 that causes an amino acid substitution (P265L) had significantly reduced hyperoxia-induced inflammation compared to strains without the SNP. Further, hyperoxia-induced lung injury was significantly reduced in neonatal mice with targeted deletion of Chrm2, relative to wild-type controls. This study has important implications for understanding the mechanisms of oxidative lung injury in neonates.—Nichols, J. L., Gladwell, W., Verhein, K. C., Cho, H.-Y., Wess, J., Suzuki, O., Wiltshire, T., Kleeberger, S. R. Genome-wide association mapping of acute lung injury in neonatal inbred mice. PMID:24571919

  19. Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials

    PubMed Central

    Ma, Junpeng; Xu, Jianguo

    2015-01-01

    Objective To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI). Methods PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI. Results A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57–1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78–1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96–4.66). Conclusions Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI. PMID:26473361

  20. Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats.

    PubMed Central

    Hay, J G; Haslam, P L; Dewar, A; Addis, B; Turner-Warwick, M; Laurent, G J

    1987-01-01

    Pulmonary toxicity is an important adverse effect of bleomycin treatment. Very little is known of the mechanisms underlying the development of lung injury, especially after intravenous administration, or how it can be modulated. In this study acute lung injury induced by bleomycin has been examined in rats by assessment of alveolar lavage cell profiles, histological examination, and measurement of the total pulmonary extravascular albumin space. Intratracheal instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of the alveolar walls, and up to an eight fold increase in the total pulmonary extravascular albumin space, maximal at 72 hours. Intravenous bleomycin 0.15-5 mg produced no detectable injury when assessed in these ways. Exposure to hyperoxia (40-90%) after intravenous bleomycin, however, induced lung injury similar to that produced by intratracheal bleomycin. A much more severe injury followed administration of intravenous bleomycin after an exposure to hyperoxia, which itself resulted in lung injury; but lung injury was still detectable after bleomycin when the exposure to hyperoxia was insufficient to induce changes in control animals. Lung injury was not observed when the exposure to hyperoxia preceded bleomycin treatment. These results indicate the importance of oxygen in the pathways leading to acute lung injury following intravenous bleomycin. We conclude that exposure to oxygen might induce lung injury during and after bleomycin treatment, and suggest that in these circumstances oxygen therapy should be kept to a minimum. PMID:2443992

  1. Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats

    PubMed Central

    Rodrigues, Cecilia M. P.; Solá, Susana; Nan, Zhenhong; Castro, Rui E.; Ribeiro, Paulo S.; Low, Walter C.; Steer, Clifford J.

    2003-01-01

    Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, modulates cell death by interrupting classic pathways of apoptosis. Intracerebral hemorrhage (ICH) is a devastating acute neurological disorder, without effective treatment, in which a significant loss of neuronal cells is thought to occur by apoptosis. In this study, we evaluated whether TUDCA can reduce brain injury and improve neurological function after ICH in rats. Administration of TUDCA before or up to 6 h after stereotaxic collagenase injection into the striatum reduced lesion volumes at 2 days by as much as 50%. Apoptosis was ≈50% decreased in the area immediately surrounding the hematoma and was associated with a similar inhibition of caspase activity. These changes were also associated with improved neurobehavioral deficits as assessed by rotational asymmetry, limb placement, and stepping ability. Furthermore, TUDCA treatment modulated expression of certain Bcl-2 family members, as well as NF-κB activity. In addition to its protective action at the mitochondrial membrane, TUDCA also activated the Akt-1/protein kinase Bα survival pathway and induced Bad phosphorylation at Ser-136. In conclusion, reduction of brain injury underlies the wide-range neuroprotective effects of TUDCA after ICH. Thus, given its clinical safety, TUDCA may provide a potentially useful treatment in patients with hemorrhagic stroke and perhaps other acute brain injuries associated with cell death by apoptosis. PMID:12721362

  2. Acute Kidney Injury Recognition and Management: A Review of the Literature and Current Evidence.

    PubMed

    Shah, Syed Raza; Tunio, Sameer Altaf; Arshad, Mohammad Hussham; Moazzam, Zorays; Noorani, Komal; Feroze, Anushe Mohsin; Shafquat, Maham; Hussain, Huma Syed; Jeoffrey, Syed Ali Hyder

    2016-01-01

    Acute renal failure is defined as a rapid decrease in the glomerular filtration rate, occurring over a period of hours to days and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. AKI is a catastrophic, life-threatening event in critically ill patients. AKI can be divided into pre-renal injury, intrinsic kidney disease (including vascular insults) and obstructive uropathies. The prognosis of AKI is highly dependent on the underlying cause of the injury. Children who have AKI as a component of multisystem failure have a much higher mortality rate than children with intrinsic renal disease. Treatment of AKI is subjected to risk stratification and ongoing damage control measures, such as patients with sepsis, exposure to nephrotoxic agents, ischemia, bloody diarrhea, or volume loss, could be helped by optimizing the fluid administrations, antibiotics possessing least nephrotoxic potential, blood transfusion where hemoglobin is dangerously low, limiting the use of nephrotoxic agents including radio contrast use, while maximize the nutrition. Acute kidney injury remains a complex disorder with an apparent differentiation in pathology between septic and nonseptic forms of the disease. Although more studies are still required, progress in this area has been steady over the last decade with purposeful international collaboration. PMID:26652074

  3. Low renal oximetry correlates with acute kidney injury after infant cardiac surgery.

    PubMed

    Owens, Gabe E; King, Karen; Gurney, James G; Charpie, John R

    2011-02-01

    Acute kidney injury (AKI) is a frequent complication after cardiopulmonary bypass surgery during infancy. Standard methods for evaluating renal function are not particularly sensitive nor are proximate indicators of renal dysfunction that allow intervention in real time. Near-infrared spectroscopy (NIRS) is a newer noninvasive technology that continuously evaluates regional oximetry and may correlate with renal injury and adverse outcomes after cardiac surgery in infants. This prospective observational study enrolled 40 infants (age, <12 months) undergoing biventricular repair. Continuous renal oximetry data were collected for the first 48 postoperative hours and correlated with postoperative course, standard laboratory data, and the occurrence of acute renal injury. Subjects with low renal oximetry (below 50% for >2 h) had significantly higher postoperative peak creatinine levels by 48 h (0.8 ± 0.4 vs. 0.52 ± 0.2; p = 0.003) and a higher incidence of AKI (50 vs. 3.1%; p = 0.003) than those with normal renal oximetry. These subjects also required more ventilator days and greater vasoactive support, and they had elevated lactate levels. Prolonged low renal near-infrared oximetry appears to correlate with renal dysfunction, decreased systemic oxygen delivery, and the overall postoperative course in infants with congenital heart disease undergoing biventricular repair. PMID:21085945

  4. Gadolinium chloride attenuates sepsis-induced pulmonary apoptosis and acute lung injury.

    PubMed

    Kishta, Osama A; Goldberg, Peter; Husain, Sabah N A

    2012-01-01

    Gadolinium chloride (GdCl3), a Kupffer cells inhibitor, attenuates acute lung injury; however, the mechanisms behind this effect are not completely elucidated. We tested the hypothesis that GdCl3 acts through the inhibition of lung parenchymal cellular apoptosis. Two groups of rats were injected intraperitoneally with saline or E. coli lipopolysaccharide. In two additional groups, rats were injected with GdCl3 24 hrs prior to saline or LPS administration. At 12 hrs, lung injury, inflammation, and apoptosis were studied. Lung water content, myeloperoxidase activity, pulmonary apoptosis and mRNA levels of interleukin-1 β , -2, -5, -6, -10 and TNF- α rose significantly in LPS-injected animals. Pretreatment with GdCl3 significantly reduced LPS-induced elevation of pulmonary water content, myeloperoxidase activity, cleaved caspase-3 intensity, and attenuated pulmonary TUNEL-positive cells. GdCl3 pre-treatment upregulated IL-1 β , -2 and -10 pulmonary gene expression without significantly affecting the others. These results suggest that GdCl3 attenuates acute lung injury through its effects on pulmonary parenchymal apoptosis. PMID:24049647

  5. Nogo-B protects mice against lipopolysaccharide-induced acute lung injury

    PubMed Central

    Xu, Wujian; Zhu, Ying; Ning, Yunye; Dong, Yuchao; Huang, Haidong; Zhang, Wei; Sun, Qinying; Li, Qiang

    2015-01-01

    Nogo-B, a member of the reticulon 4 protein family, plays a critical role in tissue repair and acute inflammation. Its role in acute lung injury (ALI) remains unclear. Here, we assessed the function of Nogo-B during tissue injury in a lipopolysaccharide (LPS)-induced ALI mouse model. We found that pulmonary Nogo-B was significantly repressed after LPS instillation in C57BL/6 mice. Over-expression of pulmonary Nogo-B using an adenovirus vector carrying the Nogo-B-RFP-3flag gene (Ad-Nogo-B) significantly prolonged the survival of mice challenged with a lethal dose of LPS. The Ad-Nogo-B-treated mice also had less severe lung injury, less alveolar protein exudation, and a higher number of macrophages but less neutrophil infiltration compared with Ad-RFP-treated mice. Interestingly, microarray analysis showed that the Ad-Nogo-B-treated mice had different gene expression profiles compared with the controls and the prominent expression of genes related to wound healing and the humoral immune response after LPS induction. Of the 49 differently expressed genes, we found that the expression of PTX3 was significantly up-regulated following Nogo-B over-expression as observed in lung tissues and RAW264.7 cells. In conclusion, Nogo-B plays a protective role against LPS-induced ALI, and this effect might be exerted through the modulation of alveolar macrophage recruitment and PTX3 production. PMID:26174362

  6. Early and widespread injury of astrocytes in the absence of demyelination in acute haemorrhagic leukoencephalitis.

    PubMed

    Robinson, Christopher A; Adiele, Reginald C; Tham, Mylyne; Lucchinetti, Claudia F; Popescu, Bogdan F G H

    2014-01-01

    Acute hemorrhagic leukoencephalitis (AHL) is a fulminant demyelinating disease of unknown etiology. Most cases are fatal within one week from onset. AHL pathology varies with the acuteness of disease. Hemorrhages, vessel fibrinoid necrosis, perivascular fibrin exudation, edema and neutrophilic inflammation are early features, while perivascular demyelination, microglial foci and myelin-laden macrophages appear later. Reactive astrocytosis is not present in early hemorrhagic non-demyelinated lesions, but is seen in older lesions. This case report presents the pathology of an AHL case with fulminant course and fatal outcome within 48 hours from presentation. Severe hemorrhages, edema and neutrophilic inflammation in the absence of circumscribed perivascular demyelination affected the temporal neocortex and white matter, hippocampus, cerebellar cortex and white matter, optic chiasm, mammillary bodies, brainstem, cranial nerve roots and leptomeninges. Perivascular end-feet and parenchymal processes of astrocytes exhibited impressive swelling in haemorrhagic but non-demyelinated white matter regions. Astrocytes were dystrophic and displayed degenerating processes. Astrocytic swellings and remnants were immunoreactive for aquaporin-4, aquaporin-1 and glial fibrillary acidic protein. These morphological changes of astrocytes consistent with injury were also observed in haemorrhagic and normal appearing cortex. Our findings reinforce that perivascular demyelination is not present early in AHL. This is the first study that highlights the early and widespread astrocytic injury in the absence of demyelination in AHL, suggesting that, similarly to neuromyelitis optica and central pontine myelinolysis, demyelination in AHL is secondary to astrocyte injury. PMID:24887055

  7. Acute Kidney Injury Recognition and Management: A Review of the Literature and Current Evidence

    PubMed Central

    Shah, Syed Raza; Tunio, Sameer Altaf; Arshad, Mohammad Hussham; Moazzam, Zorays; Noorani, Komal; Feroze, Anushe Mohsin; Shafquat, Maham; Hussain, Huma Syed; Jeoffrey, Syed Ali Hyder

    2016-01-01

    Acute renal failure is defined as a rapid decrease in the glomerular filtration rate, occurring over a period of hours to days and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. AKI is a catastrophic, life-threatening event in critically ill patients. AKI can be divided into pre-renal injury, intrinsic kidney disease (including vascular insults) and obstructive uropathies. The prognosis of AKI is highly dependent on the underlying cause of the injury. Children who have AKI as a component of multisystem failure have a much higher mortality rate than children with intrinsic renal disease. Treatment of AKI is subjected to risk stratification and ongoing damage control measures, such as patients with sepsis, exposure to nephrotoxic agents, ischemia, bloody diarrhea, or volume loss, could be helped by optimizing the fluid administrations, antibiotics possessing least nephrotoxic potential, blood transfusion where hemoglobin is dangerously low, limiting the use of nephrotoxic agents including radio contrast use, while maximize the nutrition. Acute kidney injury remains a complex disorder with an apparent differentiation in pathology between septic and nonseptic forms of the disease. Although more studies are still required, progress in this area has been steady over the last decade with purposeful international collaboration. PMID:26652074

  8. Gender Differences in Awareness and Outcomes During Acute Traumatic Brain Injury Recovery

    PubMed Central

    Perrin, Paul B.; Holcomb, Megan G.; Rolston, Cynthia D.; Artman, Laura K.; Lu, Juan; Nersessova, Karine S.

    2014-01-01

    Abstract Background: Recent literature on traumatic brain injury (TBI), though mixed when reporting outcomes, seems collectively to suggest possible gender advantage for women in postinjury recovery, especially in executive functions. Hormonal neuroprotection, through female reproductive hormones, is often proposed as an underlying factor in these results. We explored potential gender differences in an aspect of executive functions, self-awareness (SA), which is often impaired after TBI, limits patient effort in critical rehabilitation, and increases caregiver burden. Methods: Within a prospective survey, repeated-measures design, 121 patients with moderate or severe TBI undergoing acute rehabilitation in a Level 1 trauma center, a family member or caregiver informant, and a treating clinician were asked to complete the Patient Competency Rating Scale (PCRS) and the Frontal Systems Behavior Scale (FrSBe) at admission and discharge. Results: Although overall, women and men with TBI showed generally similar levels of SA, women had significantly better awareness of their injury-related deficits at acute rehabilitation discharge, even when controlling for age, education, and injury severity. Conclusions: Mixed findings in this study mirror the pattern of results that dominate the published literature on gender and TBI. Gender differences in executive dysfunction may not be as large or robust as some researchers argue. In addition, complex interplays of socialization, gender-role expectations, naturally occurring male and female ability differences, and differences in access to postinjury rehabilitation are understudied potential moderators. PMID:24932911

  9. Mechanisms of Acute Kidney Injury Induced by Experimental Lonomia obliqua Envenomation

    PubMed Central

    Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O.; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R.; Ribeiro, Maria Aparecida; Guimarães, Jorge Almeida

    2015-01-01

    Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation. PMID:24798088

  10. Protective effect of catalpol on lipopolysaccharide-induced acute lung injury in mice.

    PubMed

    Fu, Kai; Piao, Taikui; Wang, Mingzhi; Zhang, Jian; Jiang, Jiuyang; Wang, Xuefeng; Liu, Hongyu

    2014-12-01

    Catalpol, an iridiod glucoside isolated from Rehmannia glutinosa, has been reported to have anti-inflammatory properties. Although anti-inflammatory activity of catalpol already reported, its involvement in lung protection has not been reported. Thus, we investigated the role of catalpol on lipopolysaccharide (LPS)-induced acute lung injury in this study. Mice acute lung injury model was induced by intranasal instillation of LPS. Catalpol was administrated 1h prior to or after LPS exposure. The severity of pulmonary injury was evaluated 12h after LPS administration. The results showed that catalpol inhibited lung W/D ratio, myeloperoxidase activity of lung samples, the amounts of inflammatory cells and TNF-α, IL-6, IL-4 and IL-1β in BALF induced by LPS. The production of IL-10 in BALF was up-regulated by catalpol. In vitro, catalpol inhibited TNF-α, IL-6, IL-4 and IL-1β production and up-regulated IL-10 expression in LPS-stimulated alveolar macrophages. Moreover, western blot analysis showed that the activation of NF-κB and MAPK signaling pathways was inhibited by catalpol. Furthermore, catalpol was found to inhibit TLR4 expression induced by LPS. In conclusion, catalpol potently protected against LPS-induced ALI. The protective effect may attribute to the inhibition of TLR4-mediated NF-κB and MAPK signaling pathways. PMID:25063711

  11. Adult stem cells for acute lung injury: remaining questions and concerns.

    PubMed

    Zhu, Ying-Gang; Hao, Qi; Monsel, Antoine; Feng, Xiao-Mei; Lee, Jae-Woo

    2013-07-01

    Acute lung injury (ALI) or acute respiratory distress syndrome remains a major cause of morbidity and mortality in hospitalized patients. The pathophysiology of ALI involves complex interactions between the inciting event, such as pneumonia, sepsis or aspiration, and the host immune response resulting in lung protein permeability, impaired resolution of pulmonary oedema, an intense inflammatory response in the injured alveolus and hypoxemia. In multiple preclinical studies, adult stem cells have been shown to be therapeutic due to both the ability to mitigate injury and inflammation through paracrine mechanisms and perhaps to regenerate tissue by virtue of their multi-potency. These characteristics have stimulated intensive research efforts to explore the possibility of using stem or progenitor cells for the treatment of lung injury. A variety of stem or progenitor cells have been isolated, characterized and tested experimentally in preclinical animal models of ALI. However, questions remain concerning the optimal dose, route and the adult stem or progenitor cell to use. Here, the current mechanisms underlying the therapeutic effect of stem cells in ALI as well as the questions that will arise as clinical trials for ALI are planned are reviewed. PMID:23578018

  12. Acute Neuronal Injury and Blood Genomic Profiles in a Nonhuman Primate Model for Ischemic Stroke

    PubMed Central

    Rodriguez-Mercado, Rafael; Ford, Gregory D; Xu, Zhenfeng; Kraiselburd, Edmundo N; Martinez, Melween I; Eterović, Vesna A; Colon, Edgar; Rodriguez, Idia V; Portilla, Peter; Ferchmin, Pedro A; Gierbolini, Lynette; Rodriguez-Carrasquillo, Maria; Powell, Michael D; Pulliam, John VK; McCraw, Casey O; Gates, Alicia; Ford, Byron D

    2012-01-01

    The goal of this study was to characterize acute neuronal injury in a novel nonhuman primate (NHP) ischemic stroke model by using multiple outcome measures. Silk sutures were inserted into the M1 segment of the middle cerebral artery of rhesus macaques to achieve permanent occlusion of the vessel. The sutures were introduced via the femoral artery by using endovascular microcatheterization techniques. Within hours after middle cerebral artery occlusion (MCAO), infarction was detectable by using diffusion-weighted MRI imaging. The infarcts expanded by 24 h after MCAO and then were detectable on T2-weighted images. The infarcts seen by MRI were consistent with neuronal injury demonstrated histologically. Neurobehavioral function after MCAO was determined by using 2 neurologic testing scales. Neurologic assessments indicated that impairment after ischemia was limited to motor function in the contralateral arm; other neurologic and behavioral parameters were largely unaffected. We also used microarrays to examine gene expression profiles in peripheral blood mononuclear cells after MCAO-induced ischemia. Several genes were altered in a time-dependent manner after MCAO, suggesting that this ischemia model may be suitable for identifying blood biomarkers associated with the presence and severity of ischemia. This NHP stroke model likely will facilitate the elucidation of mechanisms associated with acute neuronal injury after ischemia. In addition, the ability to identify candidate blood biomarkers in NHP after ischemia may prompt the development of new strategies for the diagnosis and treatment of ischemic stroke in humans. PMID:23114047

  13. Mechanisms of acute kidney injury induced by experimental Lonomia obliqua envenomation.

    PubMed

    Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R; Vieira, Maria Aparecida Ribeiro; Guimarães, Jorge Almeida

    2015-03-01

    Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. To characterize L. obliqua venom effects, we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery-based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman's space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increase the expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. In conclusion, the mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia's envenomation. PMID:24798088

  14. Cardiac Physiologic and Genetic Predictors of Hyperoxia-Induced Acute Lung Injury in Mice

    PubMed Central

    Cho, Hye-Youn; Miller-DeGraff, Laura; Walker, Christopher; Clark, James A.; Myers, Page H.; Rouse, D. Clay; Kleeberger, Steven R.

    2012-01-01

    Exposure of mice to hyperoxia produces pulmonary toxicity similar to acute lung injury/acute respiratory distress syndrome, but little is known about the interactions within the cardiopulmonary system. This study was designed to characterize the cardiopulmonary response to hyperoxia, and to identify candidate susceptibility genes in mice. Electrocardiogram and ventilatory data were recorded continuously from 4 inbred and 29 recombinant inbred strains during 96 hours of hyperoxia (100% oxygen). Genome-wide linkage analysis was performed in 27 recombinant inbred strains against response time indices (TIs) calculated from each cardiac phenotype. Reductions in minute ventilation, heart rate (HR), low-frequency (LF) HR variability (HRV), high-frequency HRV, and total power HRV were found in all mice during hyperoxia exposure, but the lag time before these changes began was strain dependent. Significant (chromosome 9) or suggestive (chromosomes 3 and 5) quantitative trait loci were identified for the HRTI and LFTI. Functional polymorphisms in several candidate susceptibility genes were identified within the quantitative trait loci and were associated with hyperoxia susceptibility. This is the first study to report highly significant interstrain variation in hyperoxia-induced changes in minute ventilation, HR, and HRV, and to identify polymorphisms in candidate susceptibility genes that associate with cardiac responses. Results indicate that changes in HR and LF HRV could be important predictors of subsequent adverse outcome during hyperoxia exposure, specifically the pathogenesis of acute lung injury. Understanding the genetic mechanisms of these responses may have significant diagnostic clinical value. PMID:22052878

  15. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study.

    PubMed

    Kabbali, Nadia; Tachfouti, Nabil; Arrayhani, Mohammed; Harandou, Mustapha; Tagnaouti, Mounia; Bentata, Yassamine; Laouad, Inass; Ramdani, Benyounes; Bayahia, Rabia; Oualim, Zouhair; Houssaini, Tarik Sqalli

    2015-01-01

    Acute kidney injury (AKI) is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%). Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases), hemorrhagic shock (six cases) and septic events (five cases). We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6%) cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care. PMID:26022044

  16. Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

    PubMed Central

    Srinivasan, Vivek J.; Mandeville, Emiri T.; Can, Anil; Blasi, Francesco; Climov, Mihail; Daneshmand, Ali; Lee, Jeong Hyun; Yu, Esther; Radhakrishnan, Harsha; Lo, Eng H.; Sakadžić, Sava; Eikermann-Haerter, Katharina; Ayata, Cenk

    2013-01-01

    Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties. PMID:23940761

  17. Contrast-Induced Acute Kidney Injury: Short and Long-term Implications

    PubMed Central

    Weisbord, Steven D.; Palevsky, Paul M.

    2011-01-01

    The intravascular administration of iodine-based contrast media remains a common cause of acute kidney injury and a leading cause of iatrogenic renal disease. Past research has elucidated the principal risk factors for contrast-induced acute kidney injury (CIAKI) and helped to establish the efficacy of various interventions for the prevention of this condition. The importance of preventing CIAKI has been underscored by a growing number of studies demonstrating strong associations of CIAKI with serious, adverse short and long-term outcomes. However, it remains unclear whether these associations are causal. This is important as considerable healthcare resources are used to prevent CIAKI. If CIAKI is a marker, but not a mediator, of serious, adverse downstream outcomes, more judicious and selective utilization of preventive care may be appropriate. Moreover, with an increasing number of studies reporting the under-utilization of coronary angiography in patients with acute coronary syndrome and underlying CKD, presumably due in part out of a fear of CIAKI, a clear understanding of whether this condition directly results in adverse downstream outcomes is essential. Careful inspection of past studies that investigated the association of CIAKI with adverse short and long-term events sheds light on their strengths and weaknesses and provides insight into how future research may be better able to characterize the short and long-term implications of this iatrogenic condition. PMID:21784279

  18. MicroRNA-mediated Th2 bias in methimazole-induced acute liver injury in mice.

    PubMed

    Uematsu, Yasuaki; Akai, Sho; Tochitani, Tomoaki; Oda, Shingo; Yamada, Toru; Yokoi, Tsuyoshi

    2016-09-15

    MicroRNA (miRNA) is a class of small non-coding RNAs containing approximately 20 nucleotides that negatively regulate target gene expression. Little is known about the role of individual miRNAs and their targets in immune- and inflammation-related responses in drug-induced liver injury. In the present study, involvement of miRNAs in the T helper (Th) 2-type immune response was investigated using a methimazole (MTZ)-induced liver injury mouse model. Co-administration of L-buthionine-S,R-sulfoximine and MTZ induced acute hepatocellular necrosis and elevated plasma levels of alanine aminotransferase (ALT) from 4h onward in female Balb/c mice. The hepatic mRNA expression of Th2 promotive factors was significantly increased concomitantly with plasma ALT levels. In contrast, the hepatic mRNA expression of Th2 suppressive factors was significantly decreased during the early phase of liver injury. Comprehensive profiling of hepatic miRNA expression was analyzed before the onset of MTZ-induced liver injury. Using in silico prediction of miRNAs that possibly regulate Th2-related genes and subsequent quantification, we identified up-regulation of expression of miR-29b-1-5p and miR-449a-5p. Among targets of these miRNAs, down-regulation of Th2 suppressive transcription factors, such as SRY-related HMG-box 4 (SOX4) and lymphoid enhancer factor-1 (LEF1), were observed from the early phase of liver injury. In conclusion, negative regulation of the expression of SOX4 by miR-29b-1-5p and that of LEF1 by miR-449a-5p is suggested to play an important role in the development of Th2 bias in MTZ-induced liver injury. PMID:27421576

  19. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers.

    PubMed

    Kjell, Jacob; Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew; Olson, Lars

    2015-11-01

    With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines--monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)--to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  20. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    PubMed Central

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage