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Sample records for necrosis pancreatica infecciosa

  1. Renal papillary necrosis

    MedlinePlus

    ... your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Ruggenenti P, Cravedi P, Remuzzi G. Microvascular and macrovascular diseases of the kidney. In: Taal MW, Chertow GM, ...

  2. Fat Necrosis and Oil Cysts

    MedlinePlus

    ... Previous Topic Granular cell tumors Next Topic Mastitis Fat necrosis and oil cysts Fat necrosis happens when ... lumpy area if it becomes bothersome. How do fat necrosis and oil cysts affect your risk for ...

  3. Subcutaneous encapsulated fat necrosis.

    PubMed

    Aydin, Dogu; Berg, Jais O

    2016-04-01

    We have described subcutaneous encapsulated fat necrosis, which is benign, usually asymptomatic and underreported. Images have only been published on two earlier occasions, in which the necrotic nodules appear "pearly" than the cloudy yellow surface in present case. The presented image may help future surgeons to establish the diagnosis peroperatively. PMID:27099753

  4. Death by necrosis

    PubMed Central

    Syntichaki, Popi; Tavernarakis, Nektarios

    2002-01-01

    Cells suffer necrotic death when exposed to extreme environmental conditions, adverse and excessive stimuli, or when deleterious mutations are encoded in their genetic material. Unlike apoptosis, which involves a highly regulated and elaborate network of biochemical events and cascades, necrosis has been considered generally to be a chaotic decadence process that effects the inexorable demise of cells otherwise not destined to die. This grim prospect is now slowly being overturned, mostly by exciting new findings in two simple model organisms, Caenorhabditis elegans and Drosophila melanogaster. Despite the wide spectrum of necrosis-initiating conditions, evidence is accumulating that execution of necrotic or neurodegenerative cell death may be carried out by a finite common set of mechanisms. PMID:12101090

  5. Walled-off pancreatic necrosis.

    PubMed

    Ramia, J M; de la Plaza, R; Quiñones-Sampedro, J E; Ramiro, C; Veguillas, P; García-Parreño, J

    2012-05-01

    Acute severe pancreatitits may be complicated by the development of 'walled-off pancreatic necrosis' (WOPN), which is characterised by a mixture of solid components and fluids on imaging studies as a consequence of organised pancreatic tissue necrosis. We present here an overview of the definition, clinical features, and diagnostic and therapeutic management of this clinical condition, which is mostly based on consensus as adequate clinical trials are lacking. PMID:22641624

  6. [A case report of progressive penile necrosis].

    PubMed

    Haba, Tomomi; Koike, Hiroshi

    2014-05-01

    The penis is provided with blood by multiple arteries. Penile necrosis is uncommon. Penile necrosis sporadically occurs in patients with progressive diabetes mellitus and/or end stage renal failure. Penile necrosis is often considered a poor prognostic feature. We present a case of penile necrosis in a patient with mild diabetes mellitus.

  7. Black Anal Canal: Acute Necrosis

    PubMed Central

    Martins, Catarina; Gonçalves, Cláudia; Alves, Paulo; Gil, Inês; Canhoto, Manuela; Silva, Filipe; Cotrim, Isabel; Amado, Cristina; Eliseu, Liliana; Vasconcelos, Helena

    2016-01-01

    Acute ischemia of the rectum or anal canal resulting in necrosis is extremely uncommon because both the rectum and the anal canal have excellent blood supplies. We present a case with spontaneous necrosis of the anal canal without rectal involvement. Surgical debridement was accomplished, and the recovery was uneventful. The patient was elderly, with probable atherosclerotic arterial disease, and presented with hypotension. Due to the lack of other precipitating factors, the hypoperfusion hypothesis seems to be the most suitable in this case. To the best of our knowledge, no similar cases have been reported in the literature on this subject.

  8. Black Anal Canal: Acute Necrosis.

    PubMed

    Barbeiro, Sandra; Martins, Catarina; Gonçalves, Cláudia; Alves, Paulo; Gil, Inês; Canhoto, Manuela; Silva, Filipe; Cotrim, Isabel; Amado, Cristina; Eliseu, Liliana; Vasconcelos, Helena

    2016-08-01

    Acute ischemia of the rectum or anal canal resulting in necrosis is extremely uncommon because both the rectum and the anal canal have excellent blood supplies. We present a case with spontaneous necrosis of the anal canal without rectal involvement. Surgical debridement was accomplished, and the recovery was uneventful. The patient was elderly, with probable atherosclerotic arterial disease, and presented with hypotension. Due to the lack of other precipitating factors, the hypoperfusion hypothesis seems to be the most suitable in this case. To the best of our knowledge, no similar cases have been reported in the literature on this subject. PMID:27626027

  9. Black Anal Canal: Acute Necrosis

    PubMed Central

    Martins, Catarina; Gonçalves, Cláudia; Alves, Paulo; Gil, Inês; Canhoto, Manuela; Silva, Filipe; Cotrim, Isabel; Amado, Cristina; Eliseu, Liliana; Vasconcelos, Helena

    2016-01-01

    Acute ischemia of the rectum or anal canal resulting in necrosis is extremely uncommon because both the rectum and the anal canal have excellent blood supplies. We present a case with spontaneous necrosis of the anal canal without rectal involvement. Surgical debridement was accomplished, and the recovery was uneventful. The patient was elderly, with probable atherosclerotic arterial disease, and presented with hypotension. Due to the lack of other precipitating factors, the hypoperfusion hypothesis seems to be the most suitable in this case. To the best of our knowledge, no similar cases have been reported in the literature on this subject. PMID:27626027

  10. Inflammatory duodenal necrosis complicating gastroschisis

    PubMed Central

    Fouad, Dina; Lee, Geraint J.; Upadhyaya, Manasvi; Drake, David

    2016-01-01

    Babies with gastroschisis have an increased risk of necrotizing enterocolitis (NEC) that can lead to short bowel syndrome, a long-term parenteral nutrition requirement, and its associated complications. To our knowledge, this is the first case report of recurrent duodenal ischemia and necrosis associated with gastroschisis in the absence of NEC totalis. PMID:27695214

  11. Inflammatory duodenal necrosis complicating gastroschisis

    PubMed Central

    Fouad, Dina; Lee, Geraint J.; Upadhyaya, Manasvi; Drake, David

    2016-01-01

    Babies with gastroschisis have an increased risk of necrotizing enterocolitis (NEC) that can lead to short bowel syndrome, a long-term parenteral nutrition requirement, and its associated complications. To our knowledge, this is the first case report of recurrent duodenal ischemia and necrosis associated with gastroschisis in the absence of NEC totalis.

  12. Minimally invasive treatment of infected pancreatic necrosis

    PubMed Central

    Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis. PMID:25653725

  13. Acute Esophageal Necrosis: An Update

    PubMed Central

    Inayat, Faisal; Hurairah, Abu; Virk, Hafeez Ul Hassan

    2016-01-01

    Acute esophageal necrosis (AEN) or “black esophagus” is a rare clinical entity with an unclear etiology. It is diagnosed at upper gastrointestinal endoscopy with the presence of strikingly black necrotic esophagus. The treatment is primarily medical, but the prognosis is generally poor due to advanced age and comorbid illnesses in patients who develop AEN. Herein, we discussed the implications of poor glycemic control in regards with AEN and undertook a literature review of this rare diagnosis. PMID:27583242

  14. Acute Esophageal Necrosis: An Update.

    PubMed

    Inayat, Faisal; Hurairah, Abu; Virk, Hafeez Ul Hassan

    2016-07-01

    Acute esophageal necrosis (AEN) or "black esophagus" is a rare clinical entity with an unclear etiology. It is diagnosed at upper gastrointestinal endoscopy with the presence of strikingly black necrotic esophagus. The treatment is primarily medical, but the prognosis is generally poor due to advanced age and comorbid illnesses in patients who develop AEN. Herein, we discussed the implications of poor glycemic control in regards with AEN and undertook a literature review of this rare diagnosis. PMID:27583242

  15. [Talus necrosis and its treatment].

    PubMed

    Trauth, J; Bläsius, K

    1988-08-01

    Aetiopathogenesis of the necrosis of the talus has not yet been definitely clarified, and neither has that of the other aseptic necroses. We were able to study the aetiopathogenesis, course of the disease and therapy in 20 of our own patients by follow-up; two of these developed necrosis of the talus in both feet. We definitely excluded patients suffering from osteochondrosis dissecans. Even though fracture of the talus is on the whole relatively rare, it remains the most frequent cause of necrosis of the talus. We also found talonecrosis after surgical correction of clubfoot, after Sudeck's disease (Sudeck-Leriche syndrome, Sudeck's atrophy or dystrophy), suppurative arthritis of the ankle joint, subtalar luxation and haematogenic osteomyelitis. Only few patients required surgery. In most cases a special boot constructed for arthrodesis patients proved sufficient. Each patient developed arthrodesis to a different degree. Depending upon the complaints and stiffening of the ankle joint or of the talo-calcanonavicular joint, the capacity of the patients to be gainfully employed was reduced by an amount between 20 and 30 per cent. PMID:2905578

  16. Acute oesophageal necrosis (black oesophagus).

    PubMed

    Galtés, Ignasi; Gallego, María Ángeles; Esgueva, Raquel; Martin-Fumadó, Carles

    2016-03-01

    A 54-year-old man was admitted to hospital after being found unconscious in his home. He had a history of alcoholism, multiple drug addictions, and type I diabetes mellitus. At admission, he had hyperglycaemia (550 mg/dL) with glucosuria and ketone bodies in the urine, along with septic shock refractory to bilateral alveolar infiltrates and severe respiratory failure. The patient died 24 hours post admission due to multiple organ failure, with diabetic ketoacidosis decompensated by possible respiratory infection in a patient with polytoxicomania. The autopsy confirmed the presence of acute bilateral bronchopneumonia, chronic pancreatitis, severe hepatic steatosis, and generalized congestive changes. At the oesophagus, acute oesophageal necrosis was evident. PMID:26949146

  17. Thermal inactivation of infectious hematopoietic necrosis and infectious pancreatic necrosis virus

    USGS Publications Warehouse

    Gosting, L.; Gould, R.W.

    1981-01-01

    A plaque assay was used to follow the inactivation kinetics of infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus in cell culture media at various temperatures. Inactivation of infectious hematopoietic necrosis virus in a visceral organ slurry was compared with that in culture media.

  18. Molecular mechanisms of regulated necrosis.

    PubMed

    Galluzzi, Lorenzo; Kepp, Oliver; Krautwald, Stefan; Kroemer, Guido; Linkermann, Andreas

    2014-11-01

    It is now clear that apoptosis does not constitute the sole genetically encoded form of cell death. Rather, cells can spontaneously undertake or exogenously be driven into a cell death subroutine that manifests with necrotic features, yet can be inhibited by pharmacological and genetic interventions. As regulated necrosis (RN) plays a major role in both physiological scenarios (e.g., embryonic development) and pathological settings (e.g., ischemic disorders), consistent efforts have been made throughout the last decade toward the characterization of the molecular mechanisms that underlie this cell death modality. Contrarily to initial beliefs, RN does not invariably result from the activation of a receptor interacting protein kinase 3 (RIPK3)-dependent signaling pathway, but may be ignited by distinct molecular networks. Nowadays, various types of RN have been characterized, including (but not limited to) necroptosis, mitochondrial permeability transition (MPT)-dependent RN and parthanatos. Of note, the inhibition of only one of these modules generally exerts limited cytoprotective effects in vivo, underscoring the degree of interconnectivity that characterizes RN. Here, we review the signaling pathways, pathophysiological relevance and therapeutic implications of the major molecular cascades that underlie RN. PMID:24582829

  19. Transpapillary drainage of pancreatic parenchymal necrosis

    PubMed Central

    Smoczyński, Marian; Adrych, Krystian

    2015-01-01

    In the last two decades the strategy of treatment of necrotizing pancreatitis has changed. Endoscopic therapy of patients with symptomatic walled-off pancreatic necrosis has a high rate of efficiency. Here we present a description of a patient with parenchymal limited necrosis of the pancreas and a disruption of the main pancreatic duct. In the treatment, active transpapillary drainage of the pancreatic necrosis (through the major duodenal papilla) was performed and insertion of an endoprosthesis into the main pancreatic duct (through the minor duodenal papilla) was applied, which enabled a bypass over the infiltration and resulted in complete resolution. PMID:26649102

  20. Post-pancreatitis Fat Necrosis Mimicking Carcinomatosis.

    PubMed

    Smith, Joshua P; Arnoletti, J Pablo; Varadarajulu, Shyam; Morgan, Desiree E

    2008-01-01

    Acute pancreatitis can result in retroperitoneal fat necrosis, typically occurring in the peripancreatic region, with extension into the transverse mesocolon, omentum and mesenteric root. When evaluated with contrast enhanced computed tomography (CECT), acute peripancreatic post necrotic collections typically become lower in attenuation over time, and often appear as homogeneous fluid collections. Saponification as a complication of fat necrosis in patients with acute pancreatitis is a well recognized clinical entity. While retroperitonal fat necrosis is commonly seen on CECT, saponification is not a prominent imaging feature. We present a case of acute pancreatitis complicated by extensive saponification of fat throughout the retroperitoneum and peritoneal lining, mimicking carcinomatosis.

  1. Role of the Mitochondrion in Programmed Necrosis

    PubMed Central

    Baines, Christopher P.

    2010-01-01

    In contrast to the “programmed” nature of apoptosis and autophagy, necrotic cell death has always been believed to be a random, uncontrolled process that leads to the “accidental” death of the cell. This dogma, however, is being challenged and the concept of necrosis also being “programmed” is gaining ground. In particular, mitochondria appear to play a pivotal role in the mediation of programmed necrosis. The purpose of this review, therefore, is to appraise the current concepts regarding the signaling mechanisms of programmed necrosis, with specific attention to the contribution of mitochondria to this process. PMID:21423395

  2. Massive tongue necrosis secondary to temporal arteritis.

    PubMed

    Roseman, B B; Granite, E

    1984-10-01

    A case of unusually massive necrosis of the tongue secondary to temporal arteritis is presented. The clinician must include temporal arteritis in the differential diagnosis of patients presenting with signs and symptoms of tongue ischemia.

  3. Retroperitoneal fat necrosis producing ureteral obstruction.

    PubMed

    Ross, J S; Prout, G R

    1976-05-01

    We present 3 cases of a rare syndrome of extrinsic ureteral obstruction produced by retroperitoneal fat necrosis and compare the medical records and histopathology to 19 cases of classic idiopathic retroperitoneal fibrosis. Clinical similarities include average age of onset in the fourth and fifth decades, male preponderance, abdominal or back pain as the presenting symptom, elevation of the blood urea concentration prior to diagnosis and tendency toward bilateral involvement. Histologically, the 2 conditions were different. Retroperitoneal fat necrosis is characterized by coalescence of fat cells into fat cysts bordered by foreign body giant cell granulomas, foam cells, light chronic inflammatory infiltrate and unimpressive fibrosis. The microscopic pathology of idiopathic retroperitoneal fibrosis is dominated by densely collagenized fibrous tissue of varying cellularity without evidence of fat necrosis. Of the 3 cases of retroperitoneal fat necrosis 2 featured prior ischiorectal abscesses and this is considered in a discussion of the etiology of this unusual cause of ureteral compression.

  4. Intracellular serpins, firewalls and tissue necrosis.

    PubMed

    Marciniak, Stefan J; Lomas, David A

    2008-02-01

    Luke and colleagues have recently attributed a new role to a member of the serpin superfamily of serine proteinase inhibitors. They have used Caenorhabditis elegans to show that an intracellular serpin is crucial for maintaining lysosomal integrity. We examine the role of this firewall in preventing necrosis and attempt to integrate this with current theories of stress-induced protein degradation. We discuss how mutant serpins cause disease either through polymerization or now, perhaps, by unleashing necrosis. PMID:18215520

  5. Retroperitoneal endoscopic debridement for infected peripancreatic necrosis.

    PubMed

    Seifert, H; Wehrmann, T; Schmitt, T; Zeuzem, S; Caspary, W F

    2000-08-19

    Standard management of infected peripancreatic necrosis consists of open surgical debridement and lavage--a traumatic intervention with substantial morbidity and mortality. As an alternative and novel approach with minimum invasiveness, we present fenestration of the gastric wall and debridement of infected necrosis by direct retroperitoneal endoscopy. In three patients, this strategy led to rapid clinical improvement and no serious complications. Transgastric endoscopic therapy may be a less traumatic alternative to surgery and should be further assessed in prospective studies.

  6. Imaging Tumor Necrosis with Ferumoxytol

    PubMed Central

    Aghighi, Maryam; Golovko, Daniel; Ansari, Celina; Marina, Neyssa M.; Pisani, Laura; Kurlander, Lonnie; Klenk, Christopher; Bhaumik, Srabani; Wendland, Michael; Daldrup-Link, Heike E.

    2015-01-01

    showed similar findings with high T1 signal in areas of tumor necrosis and low signal in areas of intracellularly compartmentalized iron. Conclusion Differential T1- and T2-enhancement patterns of USPIO in tumors enable conclusions about their intracellular and extracellular location. This information can be used to characterize the composition of the tumor microenvironment. PMID:26569397

  7. Painful fat necrosis resulting from insulin injections

    PubMed Central

    Pandit, M; Menon, V; Roberts, S; Barber, T M

    2014-01-01

    Summary The case is a 34-year-old woman with long-standing type 1 diabetes mellitus with existing follow-up in the outpatient clinic at the Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, UHCW. She had maintained good glycaemic control and glycaemic stability with basal bolus regimen for many years. She had not developed any diabetes-related complications and had no other co-morbidities. Six months ago, she presented to A&E with sudden-onset, well-localised and severe pain in the right iliac fossa, just lateral to the para-umbilical area. Her biochemistry was normal. Ultrasound scan, however, revealed a right-sided ovarian cyst, which was thought to have caused pain to her. She was discharged from A&E with simple analgesia. On subsequent gynaecological follow-up 4 weeks later, her pain remained severe and examination revealed an exquisitely tender subcutaneous nodule at the same location measuring 2 cm in diameter. Magnetic resonance imaging (MRI) scan at the time revealed a 1 cm mass in the subcutaneous adipose tissue, which co-localised to her pain. The mass demonstrated a central fat signal surrounded by a peripheral ring: observations consistent with fat necrosis. There were other smaller subcutaneous nodules also observed in the left para-umbilical area. Subsequent surgical resection of the main area of fat necrosis was performed. The patient made an excellent recovery and her pain resolved post-operatively. Histology confirmed the presence of fat necrosis. Fat necrosis is a rare complication of s.c. insulin injection. This case illustrates the importance of considering this diagnosis in patients who inject insulin and develop localised injection-site pain. Learning points Fat necrosis is a rare complication of insulin injections that can manifest with severe, persistent and well-localised pain.Fat necrosis can masquerade as other pathologies causing diagnostic confusion.The imaging modality of choice for accurate diagnosis

  8. Renal Papillary Necrosis: Role of Radiology

    PubMed Central

    Pandya, Vaidehi K.

    2016-01-01

    Renal Papillary Necrosis (RPN) is idefined as Ischemic necrobiosis of the papilla in the medulla of the kidneys. Variety of etiological factors are recognized which cause papillary necrosis, such as analgesic nephropathy, diabetes mellitus, urinary obstruction and sickle cell haemoglobinopathy. The early diagnosis of RPN is important to improve prognosis and reduce morbidity. Radiological Imaging offers early diagnosis and can guide prompt treatment of papillary necrosis and can minimize a decline in renal function. Here we report three cases of RPN with typical imaging findings. One of them was diabetic and hypertensive female with recurrent Urinary tract Infections and other was a male with no known co-morbidity. Both of them were diagnosed to have renal papillary necrosis on CT scan and were managed operatively and conservatively, respectively. Third case was a healthy female being investigated to be renal donor for her son. Here RPN was an incidental finding and was treated conservatively. Thus CT scan could detect it pre-operatively and complications due to transplantation of a kidney with papillary necrosis were avoided. So, we want to emphasize the importance of Radiology, particularly CT scanning in detection of RPN and to guide early and prompt treatment. PMID:26894147

  9. The progressive outer retinal necrosis syndrome.

    PubMed

    Holland, G N

    1994-01-01

    The progressive outer retinal necrosis (PORN) syndrome is a recently described clinical variant of necrotizing herpetic retinopathy in patients with the acquired immunodeficiency syndrome (AIDS). It is caused by varicellazoster virus infection of the retina. Its course and clinical features distinguish it from the acute retinal necrosis syndrome and CMV retinopathy. Early disease is characterized by multifocal deep retinal opacification. Lesions rapidly coalesce and progress to total retinal necrosis over a short period of time. Despite aggressive therapy with intravenous antivirial drugs, prognosis is poor; disease progression and/or recurrence is common, and the majority of patients develop no light perception vision. Total retinal detachments are common. Prophylaxis against retinal detachment using laser retinopexy has not been useful in most cases. PORN syndrome is an uncommon, but devastating complication of AIDS.

  10. The progressive outer retinal necrosis syndrome.

    PubMed

    Holland, G N

    1994-01-01

    The progressive outer retinal necrosis (PORN) syndrome is a recently described clinical variant of necrotizing herpetic retinopathy in patients with the acquired immunodeficiency syndrome (AIDS). It is caused by varicellazoster virus infection of the retina. Its course and clinical features distinguish it from the acute retinal necrosis syndrome and CMV retinopathy. Early disease is characterized by multifocal deep retinal opacification. Lesions rapidly coalesce and progress to total retinal necrosis over a short period of time. Despite aggressive therapy with intravenous antivirial drugs, prognosis is poor; disease progression and/or recurrence is common, and the majority of patients develop no light perception vision. Total retinal detachments are common. Prophylaxis against retinal detachment using laser retinopexy has not been useful in most cases. PORN syndrome is an uncommon, but devastating complication of AIDS. PMID:7852023

  11. Extensive hepatic necrosis in a premature infant.

    PubMed

    Bemmel, L A; Hack, W W; Seldenrijk, C A; Kneepkens, C M

    1992-02-01

    A fatal case of fulminant hepatic failure that occurred in the neonatal period is reported in a premature infant born after 27 4/7-weeks' gestation. Immediately after birth the infant had severe hypoxia and hypotension resulting from birth asphyxia, hypovolemic shock, and septicemia. At autopsy, histological appearance of the liver showed virtually total hepatocellular necrosis without features of fibrosis. Although the exact cause of hepatocellular injury cannot be fully ascertained, it is assumed that hypoxia and hypotension must have been the predominant factors leading to massive hepatic necrosis.

  12. Pancreatic necrosis in progressive systemic sclerosis.

    PubMed Central

    Abraham, A A; Joos, A

    1980-01-01

    Fatal pancreatic necrosis, secondary to extensive acute arteritic changes, is reported in a case of progressive systemic sclerosis. The patient presented first with hypertension and renal involvement, with active vascular lesions demonstrated by biopsy. The renal lesion at necropsy was inactive, showing the characteristic concentric fibrosis only, while the pancreatic vascular lesions were both chronic proliferative and acute in type. Images PMID:7436566

  13. Infectious pancreatic necrosis: its detection and identification

    USGS Publications Warehouse

    Wolf, K.

    1965-01-01

    Ultimate control of infectious pancreatic necrosis (IPN) in hatcheries depends largely upon learning where the virus occurs. To detect the presence of virus either susceptible fish or susceptible fish cell cultures may be used as test systems. In modern virology, it is generally agreed that cell cultures are more convenient, are usually a much more sensitive test system, and allow more rapid determinations.

  14. Finger necrosis after accidental radial artery puncture

    PubMed Central

    Kang, Jun Sik; Lee, Tae Rim; Cha, Won Chul; Shin, Tae Gun; Sim, Min Seob; Jo, Ik Joon; Song, Keun Jeong; Rhee, Joong Eui; Jeong, Yeon Kwon

    2014-01-01

    Radial artery puncture, an invasive procedure, is frequently used for critical patients. Although considered safe, severe complications such as finger necrosis can occur. Herein, we review the clinical course of finger necrosis after accidental radial artery puncture. A 63-year-old woman visited the emergency department (ED) with left second and third finger pain after undergoing intravenous (IV) access in her wrist for procedural sedation. During the IV access, she experienced wrist pain, which increased during the 12 hours prior to her ED presentation. Emergency angiography revealed a pseudoaneurysm in her left radial artery and absence of blood flow to the proper palmar digital artery. Subsequent angiointervention and urokinase thrombolysis failed. The second finger was eventually amputated owing to gangrene. Radial artery puncture can occur accidentally during IV wrist access, resulting in severe morbidity. Providers should carefully examine the puncture site and collateral flow, followed by multiple examinations to ensure distal circulation.

  15. Programmed necrosis in acute kidney injury.

    PubMed

    Linkermann, Andreas; De Zen, Federica; Weinberg, Joel; Kunzendorf, Ulrich; Krautwald, Stefan

    2012-09-01

    Programmed cell death (PCD) had been widely used synonymously to caspase-mediated apoptosis until caspase-independent cell death was described. Identification of necrosis as a regulated process in ischaemic conditions has recently changed our understanding of PCD. At least three pathways of programmed necrosis (PN) have been identified. First, receptor-interacting protein kinase 3 (RIP3)-dependent necroptosis causes organ failure following stroke, myocardial infarction and renal ischaemia/reperfusion injury. Necroptosis can be mediated either by a large intracellular caspase-8-containing signalling complex called the ripoptosome or by the RIP1-/RIP3-containing necroptosome and is controlled by a caspase-8/FLICE inhibitory protein(long) heterodimer at least in the latter case. Second, mitochondrial permeability transition mediates apoptotic or necrotic stimuli and depends on the mitochondrial protein cyclophilin D. The third PN pathway involves the poly(ADP-ribose) polymerase-calpain axis that contributes to acute kidney injury (AKI). Preclinical interference with the PN pathways therefore raises expectations for the future treatment of ischaemic conditions. In this brief review, we aim to summarize the clinically relevant PCD pathways and to transfer the basic science data to settings of AKI. We conclude that pathologists were quite right to refer to ischaemic kidney injury as 'acute tubular necrosis'. PMID:22942173

  16. Ketoconazole attenuates radiation-induction of tumor necrosis factor

    SciTech Connect

    Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R.

    1994-07-01

    Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

  17. Tracheal necrosis with surgical emphysema following thyroidectomy.

    PubMed

    Chauhan, A; Ganguly, M; Saidha, N; Gulia, P

    2009-01-01

    Tracheal necrosis after thyroidectomy is an extremely rare event with only a few published reports. We present a case of a 65-year-old male who developed rapidly progressive surgical emphysema of face and upper thorax on the seventh day following total thyroidectomy. Prompt surgical exploration of neck revealed a tracheal rent at the level of the second tracheal ring. This hole was then refashioned into a formal tracheostomy. Patient had an eventful recovery. Tracheostomy was closed by the 14th day. The complication was probably related to tracheal injury sustained due to electro-coagulation and subsequent secondary infection. PMID:19884745

  18. Tracheal necrosis with surgical emphysema following thyroidectomy.

    PubMed

    Chauhan, A; Ganguly, M; Saidha, N; Gulia, P

    2009-01-01

    Tracheal necrosis after thyroidectomy is an extremely rare event with only a few published reports. We present a case of a 65-year-old male who developed rapidly progressive surgical emphysema of face and upper thorax on the seventh day following total thyroidectomy. Prompt surgical exploration of neck revealed a tracheal rent at the level of the second tracheal ring. This hole was then refashioned into a formal tracheostomy. Patient had an eventful recovery. Tracheostomy was closed by the 14th day. The complication was probably related to tracheal injury sustained due to electro-coagulation and subsequent secondary infection.

  19. Tumor necrosis factor alpha and toxicology.

    PubMed

    Luster, M I; Simeonova, P P; Gallucci, R; Matheson, J

    1999-09-01

    The molecular cloning of a group of proteins, collectively referred to as cytokines, and including interleukins, chemokines, growth factors, colony stimulating factors, and tumor necrosis factors, has allowed for the increased understanding of the mechanisms for many disease processes as well as provided strategies for the development of novel therapies. Conceptually similar to hormones and peptides, this group of phylogenetically related molecules are also involved in various toxicological processes, including apoptosis, cell repair, and in particular inflammation. In this review, we offer a description of what many believe represents the primary regulatory cytokine, tumor necrosis factor (TNF)alpha and its role in toxicological processes. For over a decade it has been suspected that this molecule helps mediate the shock state induced by bacterial endotoxin and the wasting diathesis that typifies chronic diseases. Advances in molecular biology that have provided tools to modulate TNFalpha regulation and synthesis have allowed for the identification of additional roles for TNFalpha in homeostasis, cellular damage, and repair. This review provides a brief summary of our understanding of TNFalpha biology followed by a discussion of its role in toxicological responses. This is followed by specific examples of organ-specific and tissue-specific responses to chemical damage where TNFalpha has been implicated. The review concludes with a review of its implication in human risk assessment, particularly as it relates to genetic polymorphisms of TNFalpha expression and disease susceptibility.

  20. Mechanisms of Acetaminophen-Induced Liver Necrosis

    PubMed Central

    Roberts, Dean W.; James, Laura P.

    2010-01-01

    Although considered safe at therapeutic doses, at higher doses, acetaminophen produces a centrilobular hepatic necrosis that can be fatal. Acetaminophen poisoning accounts for approximately one-half of all cases of acute liver failure in the United States and Great Britain today. The mechanism occurs by a complex sequence of events. These events include: (1) CYP metabolism to a reactive metabolite which depletes glutathione and covalently binds to proteins; (2) loss of glutathione with an increased formation of reactive oxygen and nitrogen species in hepatocytes undergoing necrotic changes; (3) increased oxidative stress, associated with alterations in calcium homeostasis and initiation of signal transduction responses, causing mitochondrial permeability transition; (4) mitochondrial permeability transition occurring with additional oxidative stress, loss of mitochondrial membrane potential, and loss of the ability of the mitochondria to synthesize ATP; and (5) loss of ATP which leads to necrosis. Associated with these essential events there appear to be a number of inflammatory mediators such as certain cytokines and chemokines that can modify the toxicity. Some have been shown to alter oxidative stress, but the relationship of these modulators to other critical mechanistic events has not been well delineated. In addition, existing data support the involvement of cytokines, chemokines, and growth factors in the initiation of regenerative processes leading to the reestablishment of hepatic structure and function. PMID:20020268

  1. Avascular necrosis of bone complicating corticosteroid replacement therapy.

    PubMed Central

    Williams, P L; Corbett, M

    1983-01-01

    Two patients who developed widespread severe avascular necrosis of bone while on steroid replacement therapy are described. One, a diabetic, underwent yttrium-90 pituitary ablation for retinopathy and developed avascular necrosis within 18 months of starting prednisolone. The other, who had Addison's disease, developed avascular necrosis within 14 months of starting cortisol replacement therapy. Both cases came to bilateral total hip replacement. Images PMID:6859959

  2. Definition of bone necrosis by the pathologist

    PubMed Central

    Fondi, Cristina; Franchi, Alessandro

    2007-01-01

    Osteonecrosis is a common disorder that may go clinically unrecognized or may result in the collapse of the architecture of bone, determining severe anatomic alterations of the involved site. Osteonecrosis is not a specific disease entity, but rather the result of a number of conditions ultimately leading to an impairment of blood supply to the bone tissue, although there is evidence that modifications of bone remodelling activity and weakening of bone structure with formation of microfractures are implicated as well. According to the site involved and to the factors promoting its development, the morbid anatomy and histopathology of osteonecrosis show a different appearance. This review discusses the main skeletal manifestations of osteonecrosis, including subarticular avascular necrosis of the femoral head and of the knee, as well as osteonecrosis of the jaw. PMID:22460748

  3. Tumour necrosis factor in synovial exudates.

    PubMed Central

    Di Giovine, F S; Nuki, G; Duff, G W

    1988-01-01

    The actions of tumour necrosis factor (TNF) include resorption of bone and cartilage, suggesting a potential role in the pathogenesis of arthritis. TNF activity was looked for in synovial fluids from 137 patients with different rheumatic diseases. Unfractionated samples were tested in the L929 bioassay. Significant TNF activity that was neutralised by monoclonal antibody to TNF alpha occurred in 13 (30%) of 44 samples. Raised TNF levels were not associated with any particular disease type or routine laboratory markers of inflammation but were related to disease duration in osteoarthritis. The finding of biologically active TNF in symptomatic joints of arthritic patients supports the idea that it may contribute to the pathogenesis of joint damage in chronic rheumatic diseases. PMID:3263088

  4. Nicolau Syndrome: An Iatrogenic Cutaneous Necrosis

    PubMed Central

    Nischal, KC; Basavaraj, HB; Swaroop, MR; Agrawal, DP; Sathyanarayana, BD; Umashankar, NP

    2009-01-01

    Nicolau syndrome is an uncommon complication of intramuscular injection leading to variable degrees of necrosis of skin and the underlying tissues. We report here two cases of this syndrome. Our first case was a 25 year-old male who developed intense pain and purplish discoloration of the skin in the right hip after intramuscular diclofenac injection. The second case was a 60 year-old male who developed intense pain and discoloration of skin, not only at the injection site, but also on the left scapular area and left elbow after receiving chlorpheniramine maleate injection intramuscularly. These cases highlight the need for awareness about this condition and the need to exercise utmost care during the administration of any parenteral injections by dermatologists. PMID:20808597

  5. Pseudotumoral encapsulated fat necrosis with diffuse pseudomembranous degeneration.

    PubMed

    Felipo, F; Vaquero, M; del Agua, C

    2004-09-01

    An extraordinary case of encapsulated fat necrosis characterized by its large size, diffuse formation of pseudomembranes, and tendency to recur after excision is reported. A 67-year-old Caucasian woman suffering from morbid obesity was admitted for diagnosis and surgical treatment of a soft tissue mass showing a longest diameter of 14 cm and lying adjacently to the scar from previous appendicectomy. Histopathologic features were consistent with a nodular-cystic encapsulated fat necrosis with diffuse pseudomembranous transformation. Eight months after surgery, a new larger mass (longest diameter of 18 cm) sharing identical histopathologic features appeared in the same location. Encapsulated fat necrosis is a well-defined entity even though several names have been proposed for this condition, including mobile encapsulated lipoma, encapsulated necrosis, or nodular-cystic fat necrosis. Its pathogenesis seems to be related to ischemic changes secondary to previous trauma. It may occasionally show degenerative changes, including dystrophic calcifications and presence of pseudomembranes. To our knowledge, these are the first reported cases of encapsulated fat necrosis presenting as lesions of such size and showing diffuse formation of pseudomembranes; these particular features made diagnosis difficult and led to consideration of a wide range of potential diagnostic possibilities. This case expands the clinico-pathologic spectrum of membranocystic fat necrosis, including the potential ability of this subcutaneous fatty tissue abnormality to recur after surgical excision. Felipo F, Vaquero M, del Agua C. Pseudotumoral encapsulated fat necrosis with diffuse pseudomembranous degeneration.

  6. Black esophagus (acute esophageal necrosis) after spinal anesthesia.

    PubMed

    Román Fernández, A; López Álvarez, A; Fossati Puertas, S; Areán González, I; Varela García, O; Viaño López, P M

    2014-01-01

    Acute esophagic necrosis or black esophagus is an uncommon clinical entity that owes its name to the endoscopic view of the necrotic esophageal mucosa. It is always related with a critical medical condition and usually has an ischemic etiology. We report the first case of acute esophageal necrosis after a spinal anesthetic for partial hip joint arthroplasty. We discuss the underlying pathophysiological mechanisms.

  7. [Programmed necrosis: a new target for
ischemia reperfusion injury].

    PubMed

    Li, Xiaojing; Ming, Yingzi; Niu, Ying; Liu, Qianwen; Ye, Qifa

    2016-07-01

    Recent years, the researchers have found a new type of cell death, referred to programmed necrosis or necroptosis, which involves the death receptor and the ligand binds and is initiated under the inhibition of apoptosis pathway. Programmed necrosis possesses the morphological features of typical necrosis accompanied by inflammation. The receptor interacting protein kinase 1/3(RIPK1/3) can be inhibited by the specific inhibitors, such as necrostatin-1. RIPK1/3 could regulate programmed necrosis and play a key role in the process. The significance of programmed necrosis in ischemia-reperfusion injury (IRI) has been attracted great attention at present. Simultaneously, a series of studies have found it also involves in the IRI of heart, kidney, brain and retina. PMID:27592584

  8. Pathophysiology, Diagnosis, and Treatment of Radiation Necrosis in the Brain

    PubMed Central

    MIYATAKE, Shin-Ichi; NONOGUCHI, Noasuke; FURUSE, Motomasa; YORITSUNE, Erina; MIYATA, Tomo; KAWABATA, Shinji; KUROIWA, Toshihiko

    2015-01-01

    New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain. PMID:25744350

  9. Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis

    PubMed Central

    Osterberg, E. Charles; Elliott, Sean P.; Hittelman, Adam B.

    2016-01-01

    We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting.

  10. Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis

    PubMed Central

    Osterberg, E. Charles; Elliott, Sean P.; Hittelman, Adam B.

    2016-01-01

    We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting. PMID:27656309

  11. Immunization with viral antigens: infectious haematopoietic necrosis.

    PubMed

    Winton, J R

    1997-01-01

    Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease. PMID:9270850

  12. Immunization with viral antigens: infectious haematopoietic necrosis.

    PubMed

    Winton, J R

    1997-01-01

    Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease.

  13. Stimulation of neutrophils by tumor necrosis factor

    SciTech Connect

    Klebanoff, S.J.; Vadas, M.A.; Harlan, J.M.; Sparks, L.H.; Gamble, J.R.; Agosti, J.M.; Waltersdorph, A.M.

    1986-06-01

    Human recombinant tumor necrosis factor (TNF) was shown to be a weak direct stimulus of the neutrophil respiratory burst and degranulation. The stimulation, as measured by iodination, H/sub 2/O/sub 2/ production, and lysozyme release, was considerably increased by the presence of unopsonized zymosan in the reaction mixture, an effect which was associated with the increased ingestion of the zymosan. TNF does not act as an opsonin but, rather, reacts with the neutrophil to increase its phagocytic activity. TNF-dependent phagocytosis, as measured indirectly by iodination, is inhibited by monoclonal antibodies (Mab) 60.1 and 60.3, which recognize different epitopes on the C3bi receptor/adherence-promoting surface glycoprotein of neutrophils. Other neutrophil stimulants, namely N-formyl-methionyl-leucyl-phenylalanine, the Ca2+ ionophore A23187, and phorbol myristic acetate, also increase iodination in the presence of zymosan; as with TNF, the effect of these stimulants is inhibited by Mab 60.1 and 60.3, whereas, in contrast to that of TNF, their stimulation of iodination is unaffected by an Mab directed against TNF. TNF may be a natural stimulant of neutrophils which promotes adherence to endothelial cells and to particles, leading to increased phagocytosis, respiratory burst activity, and degranulation.

  14. [An infected necrosis of the chin].

    PubMed

    Muller, B S; van Goor, H F; Rosenberg, A J W P

    2016-01-01

    A 51-year-old man was referred by his dentist to a maxillofacial surgeon with complaints of illness and pain in the mandible, associated with a rapidly expanding area of black gingiva and mucosa surrounding the lower front teeth. Clinically and radiographically there was evidence of an infected necrosis of the chin and floor of mouth. Following debridement at the operating room, the patient was treated at the intensive care unit for septic shock leading to prolonged hospitalisation. Investigation of the bone marrow did not provide an explanation for pancytopenia or the severity of the illness. In addition, genetic investigation of thiopurine S-methyltransferase gene showed no mutations. This gene codes for an identically named protein enzyme that contributes in the metabolising of the medicine azathioprine, used daily for an autoimmune disease. A combination of the use of azathioprine, a folic acid deficiency and sepsis led to this exceptional course of illness. Therapeutic intervention consisted of surgical debridement and treatment of the bacteraemia. Afterwards several corrective surgeries were necessary to restore oral functions.

  15. [Torsion and necrosis of epiploic appendices of the large bowel].

    PubMed

    Timofeev, M E; Fedorov, E D; Krechetova, A P; Shapoval'iants, S G

    2014-01-01

    The features of the clinical symptoms was studied, the possibility of laparoscopy in modern diagnosis and treatment of epiploic appendices torsion and necrosis of the large bowel was assessed in the article. It was done the retrospective analysis of the medical records of 87 patients with a diagnosis of epiploic appendices torsion and necrosis of the large bowel. The patients had laparoscopic operations in our hospital in the period from January 1995 to December 2012. The clinical picture, laboratory and instrumental datas in cases of epiploic appendices torsion and necrosis were scarce and nonspecific. An abdominal pain preferentially localized in the lower divisions was the main symptom (97.7%). The instrumental methods did not allow to diagnose the torsion and necrosis of epiploic appendices in the majority of cases and all these techniques were used for the differential diagnosis with other diseases. The assumption of the presence of appendices torsion and necrosis occured just in 34.5% of cases before the operation. Diagnosis of epiploic appendices torsion and necrosis present significant difficulties on prehospital and preoperative stages. The diagnostic laparoscopy is the method of choice in unclear situations and it allows to diagnose the torsion and necrosis of epiploic appendices in 96.6% of cases. Successful surgical treatment by using laparoscopic approach is possible in 90.8% of cases.

  16. Tumor necrosis factor interaction with gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Tsai, De-Hao; Elzey, Sherrie; Delrio, Frank W.; Keene, Athena M.; Tyner, Katherine M.; Clogston, Jeffrey D.; Maccuspie, Robert I.; Guha, Suvajyoti; Zachariah, Michael R.; Hackley, Vincent A.

    2012-05-01

    We report on a systematic investigation of molecular conjugation of tumor necrosis factor-α (TNF) protein onto gold nanoparticles (AuNPs) and the subsequent binding behavior to its antibody (anti-TNF). We employ a combination of physical and spectroscopic characterization methods, including electrospray-differential mobility analysis, dynamic light scattering, polyacrylamide gel electrophoresis, attenuated total reflectance-Fourier transform infrared spectroscopy, fluorescence assay, and enzyme-linked immunosorbent assay. The native TNF used in this study exists in the active homotrimer configuration prior to conjugation. After binding to AuNPs, the maximum surface density of TNF is (0.09 +/- 0.02) nm-2 with a binding constant of 3 × 106 (mol L-1)-1. Dodecyl sulfate ions induce desorption of monomeric TNF from the AuNP surface, indicating a relatively weak intermolecular binding within the AuNP-bound TNF trimers. Anti-TNF binds to both TNF-conjugated and citrate-stabilized AuNPs, showing that non-specific binding is significant. Based on the number of anti-TNF molecules adsorbed, a substantially higher binding affinity was observed for the TNF-conjugated surface. The inclusion of thiolated polyethylene glycol (SH-PEG) on the AuNPs inhibits the binding of anti-TNF, and the amount of inhibition is related to the number ratio of surface bound SH-PEG to TNF and the way in which the ligands are introduced. This study highlights the challenges in quantitatively characterizing complex hybrid nanoscale conjugates, and provides insight on TNF-AuNP formation and activity.We report on a systematic investigation of molecular conjugation of tumor necrosis factor-α (TNF) protein onto gold nanoparticles (AuNPs) and the subsequent binding behavior to its antibody (anti-TNF). We employ a combination of physical and spectroscopic characterization methods, including electrospray-differential mobility analysis, dynamic light scattering, polyacrylamide gel electrophoresis

  17. Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

    SciTech Connect

    Chao, Samuel T.; Ahluwalia, Manmeet S.; Barnett, Gene H.; Stevens, Glen H.J.; Murphy, Erin S.; Stockham, Abigail L.; Shiue, Kevin; Suh, John H.

    2013-11-01

    The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.

  18. Incus and stapes necrosis associated with diabetes mellitus.

    PubMed

    Tüz, M; Doğru, H; Yasan, H; Döner, F; Yariktaş, M

    2006-07-01

    Chronic otitis media is often associated with ossicular defects, the most frequent being necrosis of the long process of incus. Except for infection and cholesteatoma; trauma and local pressure by chorda tympani are uncommon causes leading to incus erosion. In the literature, no case of incus necrosis has been reported associated with type II diabetes mellitus (DM). A patient is presented in this report with incus and stapes suprastructure necrosis and associated type II DM who was admitted to the out-patient clinic with complaints of conductive hearing loss. PMID:16834796

  19. Practical quantification of necrosis in histological whole-slide images.

    PubMed

    Homeyer, André; Schenk, Andrea; Arlt, Janine; Dahmen, Uta; Dirsch, Olaf; Hahn, Horst K

    2013-06-01

    Since the histological quantification of necrosis is a common task in medical research and practice, we evaluate different image analysis methods for quantifying necrosis in whole-slide images. In a practical usage scenario, we assess the impact of different classification algorithms and feature sets on both accuracy and computation time. We show how a well-chosen combination of multiresolution features and an efficient postprocessing step enables the accurate quantification necrosis in gigapixel images in less than a minute. The results are general enough to be applied to other areas of histological image analysis as well. PMID:23796718

  20. Plaquing procedure for infectious hematopoietic necrosis virus

    USGS Publications Warehouse

    Burke, J.A.; Mulcahy, D.

    1980-01-01

    A single overlay plaque assay was designed and evaluated for infectious hematopoietic necrosis virus. Epithelioma papillosum carpio cells were grown in normal atmosphere with tris(hydroxymethyl)aminomethane- or HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered media. Plaques were larger and formed more quickly on 1- to 3-day-old cell monolayers than on older monolayers. Cell culture medium with a 10% addition of fetal calf serum (MEM 10) or without serum (MEM 0) were the most efficient virus diluents. Dilution with phosphate-buffered saline, saline, normal broth, or deionized water reduced plaque numbers. Variations in the pH (7.0 to 8.0) of a MEM 0 diluent did not affect plaque numbers. Increasing the volume of viral inoculum above 0.15 ml (15- by 60-mm plate) decreased plaquing efficiency. Significantly more plaques occurred under gum tragacanth and methylcellulose than under agar or agarose overlays. Varying the pH (6.8 to 7.4) of methylcellulose overlays did not significantly change plaque numbers. More plaques formed under the thicker overlays of both methylcellulose and gum tragacanth. Tris(hydroxymethyl)aminomethane and HEPES performed equally well, buffering either medium or overlay. Plaque numbers were reduced when cells were rinsed after virus adsorption or less than 1 h was allowed for adsorption. Variation in adsorption time between 60 and 180 min did not change plaque numbers. The mean plaque formation time was 7 days at 16 degrees C. The viral dose response was linear when the standardized assay was used.

  1. Post-facelift flap necrosis treatment using charged polystyrene microspheres

    PubMed Central

    Weissman, Oren; Farber, Nimrod; Remer, Eric; Tessone, Ariel; Trivizki, Omer; Bank, Jonathan; Winkler, Eyal; Zilinsky, Isaac; Haik, Josef

    2013-01-01

    BACKGROUND: Flap necrosis following facial rhytidectomy constitutes a vexing and grievous complication to the patient and the surgeon. Treatment modalities that can expedite wound healing and re-epithelialization rates are highly desired. OBJECTIVES: To assess wound healing and re-epithelialization rates of open wounds following postrhytidectomy flap necrosis treated with commercially available charged polystyrene microspheres (Polyheal-1, Polyheal Ltd, Israel). METHODS: Flap necrosis following rhytidectomy with open wounds in three female patients were treated using dressings soaked with Polyheal-1. Wound closure rates were documented. RESULTS: The wounds demonstrated both accelerated granulation tissue formation and rapid re-epithelialization rates. No complications or side effects were encountered. CONCLUSIONS: Charged polystyrene microspheres may offer a new and efficacious way to treat open wounds due to flap necrosis following facial rhytidectomy. Further research with larger patient numbers is still needed to verify these findings. PMID:24431937

  2. Toe Necrosis, Etiologies and Management, a Case Series

    PubMed Central

    Issa, Abdelfatah Abou; Newman, Mackenzie; Simman, Richard

    2014-01-01

    Toe necrosis may have vast different etiologies. These include ischemia, embolus, and others. (1) The most common etiology is ischemia. It is a reduction in blood supply to a viable tissue that can lead to susceptibility to infection and tissue death. Peripheral ischemia, which is rooted in the lower limbs, is a major risk factor for toe necrosis because the basal metabolic requirements of tissue are not being sufficiently met. As a result, pain, ulcers, and gangrene commonly occur. (2) Other causes of direct and indirect toe necrosis and related lower limb gangrene include mechanical trauma, infectious, pharmacological sensitivity, cancer, blue toe syndrome, and other granulomatous diseases, such as Churg-Strauss syndrome. We present a case series of toes necrosis which resulted from different etiologies and their management. PMID:26199887

  3. Renal papillary necrosis and pyelonephritis accompanying fenoprofen therapy.

    PubMed

    Husserl, F E; Lange, R K; Kantrow, C M

    1979-10-26

    Renal papillary necrosis occurred after fenoprofen calcium administration in a patient with systemic lupus erythematosus and urinary tract infection. Possible mechanisms of renal damage may be hypersensitivity, decreased blood flow, and decreased production of a prostaglandin E-like substance.

  4. Cerebral radiation necrosis: diagnostic challenge and clinical management.

    PubMed

    Eisele, S C; Dietrich, J

    2015-09-01

    Cerebral radiation is an indispensable cornerstone in the treatment of many primary and metastatic brain tumors. However, besides its desired therapeutic effect on tumor cells, a significant proportion of patients will experience neurotoxic side effects as the consequence of radiotherapy. Radiation necrosis can result in progressive neurological symptoms and radiographic changes. To differentiate radiation necrosis from progressive tumor based on imaging can pose a diagnostic challenge because the MRI characteristics may be similar in both situations. Therefore, surgical biopsy and pathological confirmation is sometimes necessary to guide further management. Effective treatment options for cerebral radiation necrosis exist and should be offered to symptomatic patients. A better understanding of the cellular and molecular processes underlying the development of radiation necrosis is necessary to prevent and minimize radiation-associated morbidity and to improve treatment strategies.

  5. Chronic renal insufficiency from cortical necrosis induced by arsenic poisoning.

    PubMed

    Gerhardt, R E; Hudson, J B; Rao, R N; Sobel, R E

    1978-08-01

    A 39-year-old man had anuria and azotemia and was found to be suffering from acute arsenic poisoning. After two peritoneal dialyses, partial renal function returned, and the patient has survived for five years without dialysis. Renal cortical necrosis was demonstrated by renal biopsy and renal calcification. We suggest that arsenic be added to the list of substances capable of causing renal cortical necrosis and recommend consideration of this complication in cases of arsenical poisoning.

  6. Skin and Neourethral Necrosis in Staged Hypospadias Repair

    PubMed Central

    Mahdavi, Alireza; Sarafi, Mehdi

    2016-01-01

    Complications in hypospadias surgery are not uncommon however penile skin or flap necrosis is rarely reported. Ischemia of the flap or graft is a major complication in two stage repair of hypospadias. A 2-year old boy with proximal penile hypospadias, operated earlier for chordee correction and urethral plate formation with a preputial flap, presented for stage 2 repair. Ten days after surgery patient developed skin and neourethral necrosis. Early debridement was done followed by coverage with scrotal flaps. PMID:27398320

  7. Robotic cystogastrostomy and debridement of walled-off pancreatic necrosis.

    PubMed

    Nassour, Ibrahim; Ramzan, Zeeshan; Kukreja, Sachin

    2016-09-01

    Walled-off pancreatic necrosis is a known complication of acute pancreatitis and requires intervention if symptomatic or complicated. Laparoscopic cystogastrostomy as a minimally invasive surgical intervention has been well-described in surgical literature but data on a robotic approach is limited. Here we report a case of robotic cystogastrostomy and debridement of walled-off pancreatic necrosis in a patient with a history of severe biliary pancreatitis. PMID:27039191

  8. Erythromelalgia with subsequent digital necrosis, glomerulonephritis, and antiphospholipid antibodies.

    PubMed

    Paira, Sergio; Cassano, Gustavo; Korol, Virginia; Ortiz, Alberto; Roverano, Susana

    2005-08-01

    Erythromelalgia is a condition of extremities characterized by redness, increased temperature, and burning pain. We describe the first reported case of erythromelalgia in a young woman with digital necrosis and mesangial nephritis associated with antiphospholipid antibodies. The symptoms and necrosis completely resolved with treatment with corticosteroids. We discuss the differential diagnosis of this entity and highlight the importance of a follow up of these patients, because erythromelalgia may precede a myeloproliferative disorder or systemic lupus erythematosus by months or years.

  9. Tumour necrosis factors in childhood asthma.

    PubMed

    Najam, F I; Giasuddin, A S; Shembesh, A H

    2001-03-01

    Tumour necrosis factor-alpha (TNF alpha) and TNF beta levels in serum were measured by enzyme immunoassays in 64 Libyan children (age: 1-12 years, sex: 39 males, 25 females) with mild to moderately severe asthma (Group A). Among these patients, 35 had active disease (AA) and 29 had inactive disease (NA). According to age range, 20, 21 and 23 patients were between 1-3 years (A1), > 3-5 years (A2) and > 5-12 years (A3) respectively. A1 had 9 and 11 patients with active (AA1) and inactive (NA1) disease; A2 had 10 and 11 patients with active (AA2) and inactive (NA2) disease; A3 had 16 and 7 patients with active (AA3) and inactive (NA3) disease respectively. Age-matched comparisons was made with 57 healthy children (age: 1-12 years; sex: 30 males, 27 females) (Group B). Among the controls, 15, 19 and 23 children were between 1-3 years (B1), > 3-5 years (B2) and > 5-12 years (B3) respectively. It was observed that serum mean TNF alpha level was significantly higher in patients, while TNF beta levels was normal (A vs B-TNF alpha P < 0.001, TNF beta: P > 0.1). The TNF alpha level was elevated significantly in active disease, while it was normal in inactive disease (AA, NA, B: P = 0.0001; AA vs NA; P < 0.0001; NA vs B: P > 0.05) and TNF beta levels were normal in both groups (AA, NA, B: P = 0.25). Further, TNF alpha levels were significantly higher in all age ranges but in patients with active disease only (AA1, NA1, B: P = 0.0008; AA2, NA2, B: P = 0.0003; AA3, NA3, B: P = 0.0396). TNF alpha may therefore be involved in the pathophysiology of asthma possibly through various proinflammatory mechanisms.

  10. Effect of bevacizumab on radiation necrosis of the brain

    SciTech Connect

    Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A. . E-mail: vlevin@mdanderson.org

    2007-02-01

    Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% ({+-}22 SD), and the average change in the FLAIR images was 60% ({+-}18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg ({+-}3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment.

  11. The Extracellular Matrix Regulates Granuloma Necrosis in Tuberculosis.

    PubMed

    Al Shammari, Basim; Shiomi, Takayuki; Tezera, Liku; Bielecka, Magdalena K; Workman, Victoria; Sathyamoorthy, Tarangini; Mauri, Francesco; Jayasinghe, Suwan N; Robertson, Brian D; D'Armiento, Jeanine; Friedland, Jon S; Elkington, Paul T

    2015-08-01

    A central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism of tuberculosis pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. In human tuberculosis granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. In mice, transgenic expression of human matrix metalloproteinase 1 causes caseous necrosis, the pathological hallmark of human tuberculosis. Collagen destruction is the principal pathological difference between humanised mice and wild-type mice with tuberculosis, whereas the release of proinflammatory cytokines does not differ, demonstrating that collagen breakdown may lead to cell death and caseation. To investigate this hypothesis, we developed a 3-dimensional cell culture model of tuberculosis granuloma formation, using bioelectrospray technology. Collagen improved survival of Mycobacterium tuberculosis-infected cells analyzed on the basis of a lactate dehydrogenase release assay, propidium iodide staining, and measurement of the total number of viable cells. Taken together, these findings suggest that collagen destruction is an initial event in tuberculosis immunopathology, leading to caseous necrosis and compromising the immune response, revealing a previously unappreciated role for the extracellular matrix in regulating the host-pathogen interaction. PMID:25676469

  12. ACUTE HEPATIC NECROSIS INDUCED BY BRUCELLA INFECTION IN HYPERTHYROID MICE

    PubMed Central

    Bradley, G. Mary; Spink, Wesley W.

    1959-01-01

    When small numbers of Brucella melitensis were inoculated into ABC mice, occasional hepatic granulomas without necrosis were demonstrated. The greatest multiplication of brucellae was detected in the spleens. Because it had been previously observed that ACTH or cortisone markedly accelerated the multiplication of brucellae in the livers of infected mice with destruction of liver cells, it was considered that triiodothyronine might likewise exaggerate a brucella infection by stimulating endogenous adrenal secretion. Although adrenal hypertrophy was produced, infection of mice treated with triiodothyronine resulted in severe hepatic necrosis or infarcts without the multiplication of brucellae in either the livers or spleens. The lesions were not encountered in untreated infected mice or in control mice treated with triiodothyronine. The necrosis was associated with minimal inflammatory reaction. The necrosis was not induced in mice treated with triiodothyronine and given brucella endotoxin. The precise genesis of the acute hepatic necrosis cited in these experiments remains undefined. Triiodothyronine did not cause deaths in mice infected with Br. melitensis. The infection was neither enhanced nor suppressed. PMID:13803714

  13. Apoptosis, oncosis, and necrosis. An overview of cell death.

    PubMed Central

    Majno, G.; Joris, I.

    1995-01-01

    The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7856735

  14. Cell death by necrosis, a regulated way to go.

    PubMed

    Henriquez, Mauricio; Armisén, Ricardo; Stutzin, Andrés; Quest, Andrew F G

    2008-05-01

    Apoptosis is a programmed form of cell death with well-defined morphological traits that are often associated with activation of caspases. More recently evidence has become available demonstrating that upon caspase inhibition alternative programs of cell death are executed, including ones with features characteristic of necrosis. These findings have changed our view of necrosis as a passive and essentially accidental form of cell death to that of an active, regulated and controllable process. Also necrosis has now been observed in parallel with, rather than as an alternative pathway to, apoptosis. Thus, cell death responses are extremely flexible despite being programmed. In this review, some of the hallmarks of different programmed cell death modes have been highlighted before focusing the discussion on necrosis. Obligatory events associated with this form of cell death include uncompensated cell swelling and related changes at the plasma membrane. In this context, representatives of the transient receptor channel family and their regulation are discussed. Also mechanisms that lead to execution of the necrotic cell death program are highlighted. Emphasis is laid on summarizing our understanding of events that permit switching between cell death modes and how they connect to necrosis. Finally, potential implications for the treatment of some disease states are mentioned. PMID:18473819

  15. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis.

    PubMed

    Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE -/- mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come.

  16. Thymic necrosis following oral inoculation of mouse thymic virus.

    PubMed

    Morse, S S

    1989-11-01

    Mouse thymic virus (MTLV;ICTV designation murid herpesvirus 3) infects developing T lymphocytes of neonatal mice, causing thymic necrosis and acute immunosuppression. Infected animals shed virus indefinitely. However, although transmission in nature is presumably by contact and is likely to involve the oral-nasal route, virtually all experimental studies with MTLV have used systemic (intraperitoneal) inoculation. In order to determine whether systemic inoculation causes artifacts in pathogenesis of the infection, effects of intraperitoneal and oral-nasal inoculation were compared in newborn mice. Thymic necrosis occurred with either route of inoculation, although rate of infection was lower with oral inoculation, varying from about 20% to 67%. There were no gross differences in pathogenesis. Orally infected animals seroconverted and shed virus. These data indicate that the apparent lymphotropism of thymic virus, and induction of thymic necrosis, are not dependent on route of inoculation.

  17. Indium-111 WBC scan in acute toxic centrilobular hepatic necrosis

    SciTech Connect

    Davidson, R.M.; Dhekne, R.D.; Moore, W.H. )

    1989-12-01

    In this case of prolonged fever and abnormal liver functions, dual tracer scintigraphy with In-111 WBCs and Tc-99m SC led to a biopsy-proven diagnosis of severe acute toxic hepatitis (hepatocellular necrosis). Correlation of the Tc-99m SC scan findings with those previously reported for pseudotumors of the liver is discussed. A pseudonormal scan pattern is described for the In-111 WBC scintigraphy. Discordance between In-111 WBC and Tc-99m SC scintigraphy in this clinical setting should raise the possibility of hepatic necrosis as a diagnostic alternative to hepatic abscess.

  18. A new geographic and host record for infectious pancreatic necrosis

    USGS Publications Warehouse

    Parisot, T.J.; Yasutake, W.T.; Bressler, V.

    1963-01-01

    The occurrence of infectious pancreatic necrosis in rainbow trout (Salmo gairdneri), brook trout (Salvelinus fontinalis), and cutthroat trout (Salmo clarki) has been experimentally authenticated for the first time in the western United States. The cutthroat trout represents a new host. Brook trout fin tissue culture inoculated with bacteria-free filtrate from the diseased fish tissue showed marked degenerative changes after 24 hours. Chinook salmon (Oncorhynchus tshawytscha), kokanee (O. nerka), and silver salmon (O. kisutch) were not susceptible to the virus when inoculated. Histologically, extensive pancreatic necrosis was observed in the original and experimental materials, but striated muscle hyalinization was detected only in the original material.

  19. Genetic ablation of soluble tumor necrosis factor with preservation of membrane tumor necrosis factor is associated with neuroprotection after focal cerebral ischemia.

    PubMed

    Madsen, Pernille M; Clausen, Bettina H; Degn, Matilda; Thyssen, Stine; Kristensen, Lotte K; Svensson, Martina; Ditzel, Nicholas; Finsen, Bente; Deierborg, Tomas; Brambilla, Roberta; Lambertsen, Kate L

    2016-09-01

    Microglia respond to focal cerebral ischemia by increasing their production of the neuromodulatory cytokine tumor necrosis factor, which exists both as membrane-anchored tumor necrosis factor and as cleaved soluble tumor necrosis factor forms. We previously demonstrated that tumor necrosis factor knockout mice display increased lesion volume after focal cerebral ischemia, suggesting that tumor necrosis factor is neuroprotective in experimental stroke. Here, we extend our studies to show that mice with intact membrane-anchored tumor necrosis factor, but no soluble tumor necrosis factor, display reduced infarct volumes at one and five days after stroke. This was associated with improved functional outcome after experimental stroke. No changes were found in the mRNA levels of tumor necrosis factor and tumor necrosis factor-related genes (TNFR1, TNFR2, TACE), pro-inflammatory cytokines (IL-1β, IL-6) or chemokines (CXCL1, CXCL10, CCL2); however, protein expression of TNF, IL-1β, IL-6 and CXCL1 was reduced in membrane-anchored tumor necrosis factor(Δ/Δ) compared to membrane-anchored tumor necrosis factor(wt/wt) mice one day after experimental stroke. This was paralleled by reduced MHCII expression and a reduction in macrophage infiltration in the ipsilateral cortex of membrane-anchored tumor necrosis factor(Δ/Δ) mice. Collectively, these findings indicate that membrane-anchored tumor necrosis factor mediates the protective effects of tumor necrosis factor signaling in experimental stroke, and therapeutic strategies specifically targeting soluble tumor necrosis factor could be beneficial in clinical stroke therapy. PMID:26661199

  20. Licensed DNA Vaccines against Infectious Hematopoietic Necrosis Virus (IHNV).

    PubMed

    Alonso, Marta; Leong, Jo-Ann C

    2013-04-01

    This article reviews some of the recent patents on DNA vaccines against fish viruses, in particular against the novirhabdovirus infectious hematopoitic necrosis virus (IHNV). Although very effective in protecting fish against IHNV, only one DNA vaccine has been approved to date for use in Canada. In Europe and in US, its commercialization is restricted due to safety concerns.

  1. Comparison of Types of Cell Death: Apoptosis and Necrosis.

    ERIC Educational Resources Information Center

    Manning, Francis; Zuzel, Katherine

    2003-01-01

    Cell death is an essential factor in many biological processes including development. Discusses two types of cell death: (1) necrosis (induced by sodium azide); and (2) apoptosis (induced by sodium chromate). Illustrates key features that differ between these two types of cells death including loss of membrane integrity and internucleosomal DNA…

  2. Necrosis avid contrast agents: functional similarity versus structural diversity.

    PubMed

    Ni, Yicheng; Bormans, Guy; Chen, Feng; Verbruggen, Alfons; Marchal, Guy

    2005-08-01

    Two categories of necrosis-avid contrast agents (NACAs), namely porphyrin- and nonporphyrin-based complexes, have thus far been discovered as necrosis-targeting markers for noninvasive magnetic resonance imaging (MRI) identification of acute myocardial infarction, assessment of tissue or organ viability, and therapeutic evaluation after interventional therapies. In addition to necrosis labeling, other less-specific functions, such as first-pass perfusion, blood pool contrast effect, hepatobiliary contrast enhancement (CE), adrenal and spleen CE, and renal functional imaging, also are demonstrated with NACAs. Despite various investigations with a collection of clues in favor of certain hypotheses, the mechanisms of such a unique targetability for NACAs still remain to be elucidated. However, a few things have become clear that porphyrin-like structures are not necessary for necrosis avidity and the albumin binding is not the supposed driving force but only a parallel nonspecific feature shared by both NACAs and non-NACA substances. Although the research and development of NACAs still remain in preclinical stage at a relatively small scale, their significance rests upon striking enhancement effects, which may warrant their eventual versatile clinical applications. The present review article is intended to summarize the cumulated facts about the evolving research on this topic, to demonstrate experimental observations for better understanding of the mechanisms, to trigger broader public interests and more intensive research activities, and to advocate, toward both academics and industries, further promotion of preclinical and clinical development of this unique and promising class of contrast agents. PMID:16024991

  3. Avascular necrosis of the hip in multiple epiphyseal dysplasia

    SciTech Connect

    Mackenzie, W.G.; Bassett, G.S.; Mandell, G.A.; Scott, C.I. Jr. )

    1989-11-01

    We observed radiographic changes of avascular necrosis (AVN) of the capital femoral epiphysis in 9 hips of 11 patients with multiple epiphyseal dysplasia (MED). Plain roentgenography, bone scintigraphy, and magnetic resonance imaging (MRI) studies all revealed characteristic asymmetric changes in the presence of AVN superimposed on dysplastic femoral heads.

  4. Adult hemolytic-uremic syndrome and bone marrow necrosis

    SciTech Connect

    Hicks, C.B.; Redmond, J. III

    1984-11-01

    A case is reported of adult hemolytic-uremic syndrome in which massive bone marrow necrosis developed, a previously undescribed complication. Technetium-99m minicolloid scanning and indium-111 bone marrow scans were used to demonstrate lack of bone marrow activity in the patient. 11 references, 2 figures.

  5. Multicentric warfarin-induced skin necrosis complicating heparin-induced thrombocytopenia.

    PubMed

    Warkentin, T E; Sikov, W M; Lillicrap, D P

    1999-09-01

    Two patients developed catastrophic multicentric skin necrosis while receiving warfarin to treat venous thromboembolism complicated by immune-mediated heparin-induced thrombocytopenia (HIT). Patient 1 developed skin necrosis involving the breasts, thighs, and face, as well as venous limb gangrene and bilateral hemorrhagic necrosis of the adrenal glands, resulting in death. The second patient developed bilateral mammary necrosis necessitating mastectomies, as well as skin necrosis involving the thigh. Neither patient had an identifiable hypercoagulable syndrome, other than HIT. HIT may represent a risk factor for the development of multicentric warfarin-induced skin necrosis (WISN).

  6. First report of soybean vein necrosis disease caused by soybean vein necrosis-associated virus in Wisconsin and Iowa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several viral diseases of soybean (Glycine max) have been previously identified in the north-central U.S. soybean production area, which includes Wisconsin and Iowa (Hartman et al., 1999). In September 2012, soybean plants with symptoms similar to those reported for soybean vein necrosis disease (SV...

  7. L’ansa pancreatica: une cause rare de pancréatite aigue

    PubMed Central

    Ayari, Hichem; Rebii, Saber; Ayari, Manel; Hasni, Radhouane; Zoghlami, Ayoub

    2012-01-01

    L’ansa pancréatica est une voie de communication accessoire entre le canal de Wirsung et un conduit pancréatique accessoire ne présentant pas de jonction normale avec le premier. L’association entre cette variante anatomique et la pancréatite aigue dite idiopathique reste hypothétique. Nous rapportons l’observation d’un patient présentant des poussées de pancréatites récidivantes qui serait en rapport avec une Ansa pancréatica. PMID:23330024

  8. [Aseptic necrosis of the femoral head in young adults].

    PubMed

    Vasey, H M

    1984-01-01

    Aseptic necrosis of the femoral head is a well-defined entity. The underlying diseases originate from very different types of pathological conditions. Alcoholism, cortisone therapy, gout or hyperuricemia, sickle cell anaemia and others all lead, through various pathways, to the impairment of the medullary blood flow. In many instances, a compartment syndrome can be demonstrated in the femoral head. Death of the osteocytes follows bone marrow necrosis. Revascularisation originates in the periphery of the necrotic segment. Vascular buds and fibroblasts invade the medullary space. New bone is laid over the necrotic trabeculae. Mechanical failure results from changes in the bony framework at three different levels. The subchondral boneplate may be weakened by the process of revascularisation, the necrotic trabeculae may fail because of diminished stiffness and strength, and overloading has been demonstrated at the junction between dead and living bone. Elevation of the intramedullary pressure is the first objective sign of impending or established bone necrosis. Scintigraphy with Technetium 99 m - Sulphur colloid can now show the early stages of marrow necrosis. Roentgenographic changes only appear in a later phase of the disease. Aseptic necrosis must be considered as involving both hips, unless proven otherwise. Attention given to the "silent hip" may allow salvage and prevent the occurrence of osteo-arthritic changes leaving merely unilateral disease. As long as the geometrical shape of the femoral head is maintained operation may well prove useful. The aim at this stage is to prevent collapse. It is impossible to know in the early stages whether mechanical failure will occur, but there is general agreement that the femoral head will eventually undergo deformation. A spherical epiphysis is therefore considered a success. All the conservative methods aim to decompress the medullary cavity. Core biopsy, curettage, bone grafting and intertrochanteric osteotomy all have

  9. Breast necrosis induced by the use of coumadin: case report and review of literature

    PubMed Central

    Ejzenberg, Dani; Neusquen, Lucienne Pereira Del Grossi; Rolnik, Daniel Lorber; Lozinsky, Adriana Chebar; Piato, José Roberto Morales

    2015-01-01

    The coumadin-induced skin necrosis is rare and occurs more frequently in the breasts, thighs and buttocks. We describe the first case of coumadin necrosis of the breast in Brazil in a 62-year-old patient. PMID:26018146

  10. [APOPTOSIS AND NECROSIS OF CIRCULATING NEUTROPHILS IN PATIENTS WHILE HIGH RISK OF POSTOPERAIVE PERITONITIS OCCURRENCE].

    PubMed

    Sheyko, V D; Sytnik, D A; Shkurupiy, O O

    2015-11-01

    Processes of apoptosis and necrosis of peripheral neutrophils were investigated in 43 patients, operated on for an acute abdominal organs diseases on the first and fourth postoperative days. Changes of apoptosis and necrosis processes in peripheral neutrophils in dynamics were established. Unfavorable course of early postoperative period in patients with initial high and average risk of postoperative peritonitis occurrence was accompanied by shift in necrosis/apoptosis ratio towards necrosis of peripheral neutrophils.

  11. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

    PubMed

    Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

    2015-01-01

    We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. PMID:25948844

  12. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    PubMed

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-01-01

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. PMID:27511757

  13. The combination of breast necrosis and chylothorax following the OPCAB

    PubMed Central

    Sabzi, Feridoun; Yaghoubi, Alireza

    2016-01-01

    Due to long term patency, the internal mammary artery is considered as a conduit of choice for revascularization of the left anterior descending coronary artery. The internal mammary artery and its accessory branches in addition to perfusing the chest wall structures also contributes to supplying, part of the female breast arteries. In addition, due to the accompaniment of thoracic duct branches with the left internal mammary artery, harvesting may be associated with injury to these branches and contribute to chylothorax. We report a rare case of chylothorax and the breast necrosis following the coronary artery bypass grafting. The chylothorax was started in the second postoperative day and ceased gradually in the 12th day of operation. The breast necrosis appeared in the 3th weeks of operation with pain, and tenderness and black skin color change. The patient underwent total mastectomy in the 4th weeks of operation. PMID:27493707

  14. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

    PubMed

    Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

    2015-05-06

    We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started.

  15. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    PubMed

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-08-10

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids.

  16. Percutaneous debridement of posttraumatic infected major hepatic necrosis.

    PubMed

    Sacks, David; Ong, Adrian; Fernandez, Forrest

    2014-08-01

    Although percutaneous drainage of liver abscesses has long been the standard of care, percutaneous drainage of infected necrotic liver tissue is usually used only to stabilize a patient's condition in the setting of sepsis before surgical debridement is ultimately required, frequently in the form of a hepatic lobectomy. The present report describes three cases of curative percutaneous drainage and percutaneous debridement of posttraumatic infected major hepatic necrosis. Techniques used included catheter suction, lavage, and foreign body retrieval.

  17. Diagnosis of delayed cerebral radiation necrosis following proton beam therapy

    SciTech Connect

    Kaufman, M.; Swartz, B.E.; Mandelkern, M.; Ropchan, J.; Gee, M.; Blahd, W.H. )

    1990-04-01

    A 27-year-old man developed delayed cerebral radiation necrosis following proton beam therapy to an arteriovenous malformation. Neuroimaging with technetium 99m diethylenetriamine penta-acetic acid and positron emission tomographic scanning with fludeoxyglucose F 18 aided in his evaluation. Significant improvement of his neurologic deficits resulted from corticosteroid therapy. Clinical resolution was corroborated by serial computed tomographic scans demonstrating regression of the abnormality (a mass lesion). Various facets of radiation injury are discussed, including pathogenesis, risk factors, diagnosis, and therapy.

  18. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    PubMed Central

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Introduction Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. Case Report A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment. PMID:24926266

  19. [Morphologic analysis of a case of Sheehan's postpartal hypophyseal necrosis].

    PubMed

    Jovanovic, R; Stevanović, G

    1979-01-01

    The post-mortem finding of a 39-year-old woman with the Sheehan postpartal necrosis of the hypophysis is described. This was the only such case of 16,580 obductions of women in the period from 1961 to 1976. The cause of death was cerebral encephalomalacia and non-specific bronchopneumonia. The death occurred five years after the last delivery and almost three years after the established clinical diagnosis.

  20. Disseminated intravascular coagulation and hepatocellular necrosis due to clove oil.

    PubMed

    Brown, S A; Biggerstaff, J; Savidge, G F

    1992-10-01

    We describe the case of a 2-year-old child who suffered from disseminated intravascular coagulation (DIC) and hepatocellular necrosis, following ingestion of clove oil. The patient was treated with heparin and fresh frozen plasma, and, following specific haemostasis assays, with appropriate coagulation factor and inhibitor concentrates. The case demonstrates how this approach can be successfully used in the management of DIC with coexisting liver failure. PMID:1450336

  1. A case of hypoglycemic brain injuries with cortical laminar necrosis.

    PubMed

    Lee, Byung-Wan; Jin, Eun Sun; Hwang, Hyung-Sik; Yoo, Hyung-Joon; Jeong, Je Hoon

    2010-06-01

    We report a case of 68-yr-old male who died from brain injuries following an episode of prolonged hypoglycemia. While exploring controversies surrounding magnetic resonance imaging (MRI) findings indicating the bad prognosis in patients with hypoglycemia-induced brain injuries, we here discuss interesting diffusion-MRI of hypoglycemic brain injuries and their prognostic importance focusing on laminar necrosis of the cerebral cortex.

  2. Herbal hepatitis: subacute hepatic necrosis secondary to chaparral leaf.

    PubMed

    Katz, M; Saibil, F

    1990-04-01

    A 33-year-old woman developed subacute hepatic necrosis after several months of ingestion of Chaparral Leaf, an herbal product. Symptoms first appeared 3 months after she began taking the tablets. The patient unwittingly carried out a clinical challenge by reducing, then increasing, the dose of pills. The public and the medical profession must be wary of all "harmless" nonprescription medications, whether purchased in pharmacies or elsewhere.

  3. Carrot yellow leaf virus Is Associated with Carrot Internal Necrosis

    PubMed Central

    Adams, Ian P.; Skelton, Anna; Macarthur, Roy; Hodges, Tobias; Hinds, Howard; Flint, Laura; Nath, Palash Deb; Boonham, Neil; Fox, Adrian

    2014-01-01

    Internal necrosis of carrot has been observed in UK carrots for at least 10 years, and has been anecdotally linked to virus infection. In the 2009 growing season some growers had up to 10% of yield with these symptoms. Traditional diagnostic methods are targeted towards specific pathogens. By using a metagenomic approach with high throughput sequencing technology, other, as yet unidentified causes of root necrosis were investigated. Additionally a statistical analysis has shown which viruses are most closely associated with disease symptoms. Carrot samples were collected from a crop exhibiting root necrosis (102 Affected: 99 Unaffected) and tested for the presence of the established carrot viruses: Carrot red leaf virus (CtRLV), Carrot mottle virus (CMoV), Carrot red leaf associated viral RNA (CtRLVaRNA) and Parsnip yellow fleck virus (PYFV). The presence of these viruses was not associated with symptomatic carrot roots either as single viruses or in combinations. A sub-sample of carrots of mixed symptom status was subjected to MiSeq sequencing. The results from these tests suggested Carrot yellow leaf virus (CYLV) was associated with symptomatic roots. Additionally a novel Torradovirus, a novel Closterovirus and two novel Betaflexiviradae related plant viruses were detected. A specific diagnostic test was designed for CYLV. Of the 102 affected carrots, 98% were positive for CYLV compared to 22% of the unaffected carrots. From these data we conclude that although we have yet to practically demonstrate a causal link, CYLV appears to be strongly associated with the presence of necrosis of carrots. PMID:25365290

  4. Cerebral radiation necrosis following treatment of extracranial malignancies

    SciTech Connect

    Glass, J.P.; Hwang, T.L.; Leavens, M.E.; Libshitz, H.I.

    1984-11-01

    Nine patients with cerebral radiation necrosis following radiation therapy for extracranial neoplasms were seen at MD Anderson Hospital between 1956 and 1982. The diagnosis was confirmed at autopsy in one case, by surgical intervention in six cases, and strongly suspected based upon CT scan findings and radiation records in two cases. The world literature is reviewed, and diagnostic criteria using the CT scan and radiation doses presented.

  5. Necrosis and apoptosis in Trichinella spiralis-mediated tumour reduction

    PubMed Central

    Vasilev, Sasa; Ilic, Natasa; Gruden-Movsesijan, Alisa; Vasilijic, Sasa; Bosic, Martina

    2015-01-01

    It is known that infection with different pathogens, including helminths, can alter the progression of malignant or other diseases. We studied the effect of chronic Trichinella spiralis infection or muscle larvae excretory-secretory (ES L1) antigens on the malignant tumour growth in the mouse melanoma model system in vivo and in vitro. Our results confirmed that chronic infection with T. spiralis possesses the capacity to slow down the progression of tumour growth, resulting in an impressive reduction in tumour size. We found that the phenomenon could, at least partially, be related to a lower level of tumour necrosis compared to necrosis present in control animals with progressive malignancy course. An increased apoptotic potential among the low percentage of cells within the total tumour cell number in vivo was also observed. ES L1 antigen, as a parasitic product that is released during the chronic phase of infection, reduced the survival and slightly, but significantly increased the apoptosis level of melanoma cells in vitro. Our results imply that powerful Trichinella anti-malignance capacity does not rely only on necrosis and apoptosis but other mechanisms through which infection or parasite products manipulate the tumor establishment and expansion should be considered. PMID:26155183

  6. A Case of Idiopathic Mesenteric Phlebosclerosis with Progressive Intestinal Necrosis.

    PubMed

    Kayano, Hajime; Nomura, Eiji; Hiraiwa, Shinichiro; Kuramoto, Toru; Yatabe, Kentaro; Machida, Takashi; Tajiri, Takuma; Mukai, Masaya; Makuuchi, Hiroyasu

    2016-01-01

    The patient was a 39-year-old woman who was referred to our department from her previous doctor with a 2-day history of right abdominal pain. Abdominal computed tomography showed wall thickening associated with calcification in the ascending colon. Contrast enhancement in the same portion of the intestinal wall was rather poor. Fluid accumulation was also seen around the intestine, so emergency surgery was performed under a provisional diagnosis of intestinal necrosis. Intestinal necrosis due to idiopathic mesenteric phlebosclerosis was diagnosed from postoperative histopathological tests. Idiopathic mesenteric phlebosclerosis displays a chronic course and in most cases conservative treatment is indicated. Bowel obstruction is common among patients who require surgical treatment, but rare cases such as the present one are also seen in which intestinal necrosis occurs. In recent years, an association with herbal medicine has been indicated as one potential cause of this disease, and this entity should be kept in mind when patients with acute abdomen and a history of taking herbal medicines are encountered. PMID:27344996

  7. A Case of Bilateral Aseptic Necrosis of the Femoral Head.

    PubMed

    Kamal, Diana; Trăistaru, Rodica; Kamal, C K; Alexandru, D O; Mogoantă, L; Grecu, D C

    2014-01-01

    Aseptic necrosis of the femoral head is a disease whose etiology is not completely elucidated and generally affects young adults aged between 30 and 50 years. In a significant number of patients bilateral disease occurs, which makes detection in its early stages constitute an important objective. We present the case of a male patient, aged 23 years, with the following risk factors: smoking and chronic alcohol consumption, who is diagnosed with aseptic necrosis of the left femoral head, ARCO stage IV, and in just six months after the diagnosis and hip arthroplasty, he suffers an injury which leads to the same diagnosis in the contralateral hip. We want to emphasize that for all patients with a high index of suspicion there should be an MRI examination, because the plane radiographs or CT are most often not relevant in detecting early signs of this condition. Diagnosis of aseptic necrosis of the femoral head in the early stages is a necessity in order to obtain an optimal result of conservative treatment.

  8. A Case of Bilateral Aseptic Necrosis of the Femoral Head

    PubMed Central

    KAMAL, DIANA; TRĂISTARU, RODICA; KAMAL, C.K.; ALEXANDRU, D.O.; MOGOANTĂ, L.; GRECU, D.C.

    2014-01-01

    Aseptic necrosis of the femoral head is a disease whose etiology is not completely elucidated and generally affects young adults aged between 30 and 50 years. In a significant number of patients bilateral disease occurs, which makes detection in its early stages constitute an important objective. We present the case of a male patient, aged 23 years, with the following risk factors: smoking and chronic alcohol consumption, who is diagnosed with aseptic necrosis of the left femoral head, ARCO stage IV, and in just six months after the diagnosis and hip arthroplasty, he suffers an injury which leads to the same diagnosis in the contralateral hip. We want to emphasize that for all patients with a high index of suspicion there should be an MRI examination, because the plane radiographs or CT are most often not relevant in detecting early signs of this condition. Diagnosis of aseptic necrosis of the femoral head in the early stages is a necessity in order to obtain an optimal result of conservative treatment. PMID:26788359

  9. Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited

    PubMed Central

    Borkowski, Brian J.; Cheema, Yaser; Shahbaz, Atta U.; Bhattacharya, Syamal K.; Weber, Karl T.

    2011-01-01

    An ongoing loss of cardiomyocytes to apoptotic and necrotic cell death pathways contributes to the progressive nature of heart failure. The pathophysiological origins of necrotic cell loss relate to the neurohormonal activation that accompanies acute and chronic stressor states and which includes effector hormones of the adrenergic nervous system. Fifty years ago, Albrecht Fleckenstein and coworkers hypothesized the hyperadrenergic state, which accompanies such stressors, causes cardiomyocyte necrosis based on catecholamine-initiated excessive intracellular Ca2+ accumulation (EICA), and mitochondrial Ca2+ overloading in particular, in which the ensuing dysfunction and structural degeneration of these organelles leads to necrosis. In recent years, two downstream factors have been identified which, together with EICA, constitute a signal–transducer–effector pathway: (i) mitochondria-based induction of oxidative stress, in which the rate of reactive oxygen metabolite generation exceeds their rate of detoxification by endogenous antioxidant defences; and (ii) the opening of the mitochondrial inner membrane permeability transition pore (mPTP) followed by organellar swelling and degeneration. The pathogenesis of stress-related cardiomyopathy syndromes is likely related to this pathway. Other factors which can account for cytotoxicity in stressor states include: hypokalaemia; ionized hypocalcaemia and hypomagnesaemia with resultant elevations in parathyroid hormone serving as a potent mediator of EICA; and hypozincaemia with hyposelenaemia, which compromise antioxidant defences. Herein, we revisit the Fleckenstein hypothesis of EICA in leading to cardiomyocyte necrosis and the central role played by mitochondria. PMID:21398641

  10. Necrosis and apoptosis in Trichinella spiralis-mediated tumour reduction.

    PubMed

    Vasilev, Sasa; Ilic, Natasa; Gruden-Movsesijan, Alisa; Vasilijic, Sasa; Bosic, Martina; Sofronic-Milosavljevic, Ljiljana

    2015-01-01

    It is known that infection with different pathogens, including helminths, can alter the progression of malignant or other diseases. We studied the effect of chronic Trichinella spiralis infection or muscle larvae excretory-secretory (ES L1) antigens on the malignant tumour growth in the mouse melanoma model system in vivo and in vitro. Our results confirmed that chronic infection with T. spiralis possesses the capacity to slow down the progression of tumour growth, resulting in an impressive reduction in tumour size. We found that the phenomenon could, at least partially, be related to a lower level of tumour necrosis compared to necrosis present in control animals with progressive malignancy course. An increased apoptotic potential among the low percentage of cells within the total tumour cell number in vivo was also observed. ES L1 antigen, as a parasitic product that is released during the chronic phase of infection, reduced the survival and slightly, but significantly increased the apoptosis level of melanoma cells in vitro. Our results imply that powerful Trichinella anti-malignance capacity does not rely only on necrosis and apoptosis but other mechanisms through which infection or parasite products manipulate the tumor establishment and expansion should be considered. PMID:26155183

  11. Clinical Manifestation of Self-Limiting Acute Retinal Necrosis

    PubMed Central

    Brydak-Godowska, Joanna; Borkowski, Piotr; Szczepanik, Szymon; Moneta-Wielgoś, Joanna; Kęcik, Dariusz

    2014-01-01

    Background The purpose of this paper was to present a case series of self-limiting, peripheral acute retinal necrosis and to demonstrate efficacy of treatment with valacyclovir in patients resistant to acyclovir. The diagnosis was made on ophthalmoscopic examination and positive serum tests for herpes viruses. Material/Methods Ten patients (6F and 4M) aged 19–55 years were diagnosed and treated for self-limiting acute retinal necrosis (ARN). The following endpoints were reported: visual outcomes, clinical features, disease progression, treatment, and complications. Patients received only symptomatic treatment because they did not consent to vitreous puncture. Results Peripheral, mild retinitis was diagnosed in all eyes at baseline. Initially, all patients were treated with systemic acyclovir (800 mg, 5 times a day), prednisone (typically 40–60 mg/day), and aspirin in an outpatient setting. In 6 patients, treatment was discontinued at 6 months due to complete resolution of the inflammatory process. Four patients with immune deficiency showed signs and symptoms of chronic inflammation. Two patients did not respond to acyclovir (2 non-responders); however, those patients were successfully treated with valacyclovir. Complete resolution of inflammatory lesions was observed in 8 patients. In 2 patients, the disease progressed despite treatment – 1 female patient after kidney transplant who stopped the prescribed medications, and 1 male patient with SLE and antiphospholipid syndrome who experienced breakthrough symptoms on-treatment. He died due to cerebral venous sinus thrombosis. Neurological complications (encephalitis and meningitis) were observed in 2 female patients. Prophylactic laser photocoagulation was performed in 1 subject. Conclusions A series of cases of self-limiting acute retinal necrosis (ARN) is presented. This clinical form of ARN can resemble toxoplasmic retinitis in some cases. Oral antiviral medications provide an effective alternative to

  12. Diarachidonoylphosphoethanolamine induces necrosis/necroptosis of malignant pleural mesothelioma cells.

    PubMed

    Kaku, Yoshiko; Tsuchiya, Ayako; Kanno, Takeshi; Nakano, Takashi; Nishizaki, Tomoyuki

    2015-09-01

    The present study investigated 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE)-induced cell death in malignant pleural mesothelioma (MPM) cells. DAPE reduced cell viability in NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H MPM cell lines in a concentration (1-100μM)-dependent manner. In the flow cytometry using propidium iodide (PI) and annexin V (AV), DAPE significantly increased the population of PI-positive and AV-negative cells, corresponding to primary necrosis, and that of PI-positive and AV-positive cells, corresponding to late apoptosis/secondary necrosis, in NCI-H28 cells. DAPE-induced reduction of NCI-H28 cell viability was partially inhibited by necrostatin-1, an inhibitor of RIP1 kinase to induce necroptosis, or knocking-down RIP1. DAPE generated reactive oxygen species (ROS) followed by disruption of mitochondrial membrane potentials in NCI-H28 cells. DAPE-induced mitochondrial damage was attenuated by cyclosporin A, an inhibitor of cyclophilin D (CypD). DAPE did not affect expression and mitochondrial localization of p53 protein in NCI-H28 cells. DAPE significantly decreased intracellular ATP concentrations in NCI-H28 cells. Overall, the results of the present study indicate that DAPE induces necroptosis and necrosis of MPM cells; the former is mediated by RIP1 kinase and the latter is caused by generating ROS and opening CypD-dependent mitochondrial permeability transition pore, to reduce intracellular ATP concentrations.

  13. Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis

    SciTech Connect

    Benjamin, I.J.; Jalil, J.E.; Tan, L.B.; Cho, K.; Weber, K.T.; Clark, W.A. )

    1989-09-01

    Treatment of rats with the beta-adrenergic agonist isoproterenol results in cardiac hypertrophy, myocyte necrosis, and interstitial cell fibrosis. Our objectives in this study have been to examine whether hypertrophy and fibrosis occur in a compensatory and reparative response to myocyte loss or whether either process may be occurring independently of myocyte loss and thus be a reactive response to adrenergic hormone stimulation. We have examined this question by evaluating each of these responses in rats treated with different doses and forms of isoproterenol administration. Myocyte necrosis was evaluated using in vivo labeling with monoclonal antimyosin for identification of myocytes with permeable sarcolemma, which was indicative of irreversible injury. Myocardial fibrosis was evaluated by morphometric point counting of Gomori-stained tissue sections and by assessment of the stimulation of fibroblast proliferation by determination of increased levels of DNA synthesis. Stimulation of fibroblast DNA synthesis was determined from DNA specific radioactivities and radioautography after pulse labeling with (3H)thymidine. The evidence provided by this study suggests that the degree and timing of myocardial hypertrophy does not follow the course of myocyte loss and, thus, appears to be either a response to altered cardiac loading or a reactive response to beta-adrenergic hormone stimulation rather than a compensation for myocyte loss. Myocardial fibrosis, on the other hand, appears to be more closely related to myocyte necrosis with respect to collagen accumulation in the same areas of the heart, its dose-response relation to the amount of isoproterenol administered, and the timing of increased DNA synthesis, or fibroblast proliferation, after myocyte loss.

  14. Interferon-γ-Induced Necrosis: An Antitumor Biotherapeutic Perspective

    PubMed Central

    Adams, Gregory P.

    2013-01-01

    Interferon (IFN)-γ—like the well-known antitumor biotherapeutic IFN-α—is a powerful antiproliferative and immune modulatory cytokine, but mixed results from clinical trials, together with issues of systemic toxicity, have dampened enthusiasm for its use in the treatment of cancer. We suggest that at least 2 factors reduce the antitumor efficacy of IFN-γ: (1) poorly understood survival mechanisms that protect most tumor cells from IFN-γ-induced direct cytotoxicity, and (2) the short half-life of IFN-γ in serum. In this review, we outline avenues to overcome both these limitations. First, we have identified the transcription factor nuclear factor-kappa B (NF-κB) as a protective mechanism against IFN-γ-induced necrosis, and disabling NF-κB allows IFN-γ to trigger RIP1 kinase-dependent programmed necrosis (or necroptosis) in otherwise resistant cells. Second, we propose that fusing IFN-γ to tumor-specific antibodies will stabilize IFN-γ in serum and target this cytokine to tumor cells. We expect that such IFN-γ–antibody chimeras (called immunocytokines), when combined with agents that neutralize tumor-intrinsic survival signals such as NF-κB, will exert potent tumoricidal activity with minimized systemic side effects. Although this review will focus on exploiting IFN-γ-induced necrosis for treatment of renal cell carcinoma, these approaches are also directly applicable to several human cancers in which IFNs have shown therapeutic potential. PMID:23570383

  15. Cocaine hepatotoxicity: a study on the pathogenesis of periportal necrosis.

    PubMed Central

    Powell, C. J.; Charles, S. J.; Mullervy, J.

    1994-01-01

    Cocaine is reported to produce either periportal or mid-zonal necrosis in mice pretreated with the enzyme inducer phenobarbitone (James et al. 1987; Powell et al. 1991; Charles & Powell 1992). Dose-response and time course experiments were performed in phenobarbitone treated male DBA/2Ha mice to study the pathogenesis of this unusual cocaine induced lesion. An increase in the dose of cocaine from 60 to 90 or 120 mg/kg produced more extensive and severe periportal and linking portal damage and elevated plasma aspartate (AST) and alanine (ALT) aminotransferases in a dose dependent manner. Scattered hepatocyte degeneration began at the edge of the periportal region and was detectable by electron microscopy within 30 minutes of administration of 60 mg/kg of cocaine, with conspicuous disorganization of the endoplasmic reticulum being one of the earliest changes. Significant elevations of plasma AST and ALT were observed 3 hours after cocaine administration and were sustained for 12 hours, at which time progressive hepatocyte damage had developed into a network of confluent necrosis at the periphery of the periportal region. The rapidity of organelle derangement and subsequent cell death, and absence of any effect on total cytochrome P-450 or FAD-mono-oxygenase levels, appear to distinguish this periportal lesion from previous reports of cocaine induced centrilobular necrosis in non-enzyme induced mice, suggesting that the two types of damage may develop by different mechanisms. The observation that periportal lesions commence at the periphery of the periportal area, progressing portalwards with increasing dose and time, offers an explanation for the previously conflicting reports of cocaine induced mid-zonal and/or periportal lesions in phenobarbitone treated mice. Images Figure 1 Figure 3 Figure 4 PMID:7734331

  16. Association of varicella zoster dermatitis with acute retinal necrosis syndrome.

    PubMed

    Browning, D J; Blumenkranz, M S; Culbertson, W W; Clarkson, J D; Tardif, Y; Gourdeau, A; Minturn, J

    1987-06-01

    The authors report seven patients in whom the acute retinal necrosis (ARN) syndrome developed shortly after cutaneous varicella zoster infection. The length of time between the skin infection and ARN varied from 5 days to 3 months. Both eyes were affected in one of seven cases. The ophthalmic branch of cranial nerve V ipsilateral to an affected eye was involved by the zoster dermatitis in only two of the seven cases. The association lends further support to the proposal that herpes zoster virus is a major cause of ARN. A history of recent zoster dermatitis should be sought in patients with ARN.

  17. Bilateral breast necrosis due to local injection of fish oil.

    PubMed

    Turk, Emin; Karagulle, Erdal; Koksal, Hande; Togan, Turhan; Erinanc, Ozgur Hilal; Dogru, Osman; Moray, Gokhan

    2013-01-01

    The breast is as aesthetically important as it is physiologically. Physicians and women have practiced various methods for breast aesthetics and augmentation. We report a female veterinarian who injected fish oil into her breast, which led to inflammation and necrosis of breast tissue. When all medical therapies failed, bilateral subcutaneous mastectomy was performed. We did not find a case in the literature where fish oil had been used for breast augmentation. However, we did find that many agents have been injected for breast augmentation, the results of which were tragic, just as the case presented herein.

  18. Cutaneous necrosis associated with the antiphospholipid syndrome and mycosis fungoides.

    PubMed

    Hill, V A; Whittaker, S J; Hunt, B J; Liddell, K; Spittle, M F; Smith, N P

    1994-01-01

    The development of extensive cutaneous necrosis in a patient with tumour-stage mycosis fungoides is described. Skin biopsies showed a lymphomatous infiltrate, and thrombosis of dermal blood vessels. Investigation revealed the presence of anticardiolipin antibodies, a lupus anticoagulant, and low free protein S, which contributed to a prothrombotic state. Antiphospholipid antibodies have been detected in non-Hodgkin's lymphoma, but clinical manifestations are uncommon. Such autoantibodies may be produced by neoplastic lymphoid cells. The frequency with which antiphospholipid antibodies occur in mycosis fungoides is currently unknown.

  19. [Protocol for the treatment of severe acute pancreatitis with necrosis].

    PubMed

    Barreda, Luis; Targarona, Javier; Rodriguez, César

    2005-01-01

    The Severe Acute Pancreatic Unit of Edgardo Rebagliati Martins National Hospital was officially created in the year 2000. Up to date, we have cared for more than 195 patients with Pancreatic Necrosis. All of them have been treated under a management protocol presented by us. This has helped us to standardize treatment and also to compare results with work groups around the world. This Protocol comes from our own experience and that of our colleagues abroad with a wide knowledge in this kind of pathology abroad, with whom we maintain close ties.

  20. BCG Induced Necrosis of the Entire Bladder Urothelium.

    PubMed

    Krönig, Malte; Jilg, Cordula; Burger, Dieter; Langer, Mathias; Timme-Bronsert, Sylvia; Werner, Martin; Wetterauer, Ulrich; Seemann, Wolfgang-Schultze

    2015-09-01

    Instillation therapy with attenuated tuberculosis bacteria (BCG) can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence.

  1. Skin necrosis caused by prallethrin-A worldwide used insecticide.

    PubMed

    Botnariu, Gina; Birsan, Cristina; Podoleanu, Cristian; Moldovan, Cosmin; Stolnicu, Simona; Chiriac, Anca

    2016-04-01

    We report a case of necrosis caused by the use of prallethrin (mosquito repellent) on the skin in a 67-year-old diabetic female patient suffering from delusions of parasitosis. Cutaneous toxicity due to pyrethroids is less known or reported, despite well-documented pyrethroid poisoning involving the gastrointestinal, respiratory, cardiac, and nervous systems. Skin irritation has been described after acute accidental exposure but, as far as we know, no data have been published on the effects of pyrethroids when applied directly to the skin. PMID:26987111

  2. Cancer treatment by ultrasound: Increasing the depth of necrosis

    NASA Astrophysics Data System (ADS)

    Melodelima, David; Cathignol, Dominique

    2004-06-01

    Tissue coagulation by high-intensity ultrasound is a well-established method of cancer treatment. It suffers, however, from insufficient depth of action in the case of deep-seated tumors where endoscopic or interstitial applicators are used. It is demonstrated here that this depth can be increased by temporarily creating cavitation bubbles in such a way that ultrasound attenuation becomes stronger in the zone where tissue heating is insufficient. In vitro experiments in liver tissue confirm that bubbles are indeed located in this zone and that the effective depth of coagulation necrosis is doubled.

  3. Digital necrosis with squamous cell carcinoma of the tonsil

    PubMed Central

    Warrier, Vinod; Ahmad, Ali; Alshatti, Yaqoub; Jafar, Ali

    2016-01-01

    Background Digital necrosis is a rare phenomenon of paraneoplastic syndrome associated with squamous cell carcinoma of the tonsil. Since 1965, more than 70 cases have been reported worldwide in the literature. Case report A 54-year-old male smoker presented with Raynaud’s phenomenon, proceeding to frank gangrene of the fingers. Working up the case finally pointed toward carcinoma of the tonsil as the underlying cause – a rare paraneoplastic manifestation. Conclusion No definite etiology has been found to be the cause of Raynaud’s phenomenon in this case of the squamous cell carcinoma of the tonsil. A brief discussion of the literature is also presented. PMID:27390535

  4. Supraspinatus Intramuscular Calcified Hematoma or Necrosis Associated with Tendon Tear

    PubMed Central

    Lädermann, Alexandre; Genevay, Muriel; Abrassart, Sophie; Schwitzguébel, Adrien Jean-Pierre

    2015-01-01

    Introduction. Rotator cuff intramuscular calcification is a rare condition usually caused by heterotopic ossification and myositis ossificans. Case Presentation. We describe a patient with voluminous calcified mass entrapped in supraspinatus muscle associated with corresponding tendon tear. Histological examination corresponded to a calcified hematoma or necrosis. Patient was surgically managed with open excision of the calcified hematoma and rotator cuff arthroscopic repair. At 6 months, supraspinatus muscle was healed, and functional outcome was good. Discussion and Conclusion. We hypothesized that supraspinatus intramuscular calcified hematoma was responsible for mechanical stress on the tendon. This association has never been described. PMID:26380138

  5. Enteritis necroticans with midgut necrosis caused by Clostridium perfringens.

    PubMed

    Clarke, L E; Diekmann-Guiroy, B; McNamee, W; Java, D J; Weiss, S M

    1994-05-01

    Enteritis necroticans is a necrotizing process manifesting as segmental gangrene of the bowel, triggered by Clostridium perfringens toxins under specific dietary conditions. It is a rare disease in developed countries and is probably underdiagnosed. A case of enteritis necroticans presenting with midgut necrosis with sepsis and hemolysis is reported herein. Bacteriologic culture of blood and peritoneal content revealed C perfringens. Dietary history, including the ingestion of meat together with sweet potatoes, should increase clinical suspicion of enteritis necroticans. Early recognition and timely surgical intervention are required for successful treatment. Clinicians are encouraged to be aware of this clinically fulminant yet rarely recognized surgical entity.

  6. [Cell therapy for aseptic necrosis of femoral head].

    PubMed

    Toguchida, Junya; Aoyama, Tomoki; Goto, Koji; Kakinoki, Ryosuke; Kasai, Yasunari

    2011-12-01

    As the clinical application of mesenchymal stem cell (MSC), we have engaged in the development of cell transplantation therapy for aseptic necrosis of femoral head. Based on the results obtained by in vitro and in vivo preclinical experiments, we established the protocol for the clinical trial combining MSC with vascularized bone grafts. The protocol was approved by IRB on November 25, 2007, and the first case was operated on February 22, 2008. Since then 10 cases have been successfully treated and were followed at least 24 months with satisfactory results.

  7. Skin Necrosis Associated with Thromboprophylaxis after Total Knee Replacement

    PubMed Central

    Karuppiah, S. V.; Johnstone, A. J.

    2014-01-01

    Thromboprophylaxis are routinely given to prevent venous thromboembolism (VTE) in patients after total hip and knee replacement surgeries. Low molecular weight heparin (LMWH) (fractioned heparin) is effective in the prevention and treatment of VTE. The predicable effect of LMWH has popularized it for routine clinical use. Although LMWH has lesser complication rate, compared to unfractioned heparin (UFH), sporadic clinical complication has been reported. We report a rare case of skin necrosis secondary to use of LMWH tinzaparin used for routine thromboprophylaxis after total knee replacement. PMID:24804131

  8. BCG Induced Necrosis of the Entire Bladder Urothelium.

    PubMed

    Krönig, Malte; Jilg, Cordula; Burger, Dieter; Langer, Mathias; Timme-Bronsert, Sylvia; Werner, Martin; Wetterauer, Ulrich; Seemann, Wolfgang-Schultze

    2015-09-01

    Instillation therapy with attenuated tuberculosis bacteria (BCG) can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence. PMID:26793538

  9. Mastectomy Weight and Tissue Expander Volume Predict Necrosis and Increased Costs Associated with Breast Reconstruction

    PubMed Central

    Yalanis, Georgia C.; Nag, Shayoni; Georgek, Jakob R.; Cooney, Carisa M.; Manahan, Michele A.; Rosson, Gedge D.

    2015-01-01

    Introduction: Impaired vascular perfusion in tissue expander (TE) breast reconstruction leads to mastectomy skin necrosis. We investigated factors and costs associated with skin necrosis in postmastectomy breast reconstruction. Methods: Retrospective review of 169 women with immediate TE placement following mastectomy between May 1, 2009 and May 31, 2013 was performed. Patient demographics, comorbidities, intraoperative, and postoperative outcomes were collected. Logistic regression analysis on individual variables was performed to determine the effects of tissue expander fill volume and mastectomy specimen weight on skin necrosis. Billing data was obtained to determine the financial burden associated with necrosis. Results: This study included 253 breast reconstructions with immediate TE placement from 169 women. Skin necrosis occurred in 20 flaps for 15 patients (8.9%). Patients with hypertension had 8 times higher odds of skin necrosis [odd ratio (OR), 8.10, P < 0.001]. Patients with TE intraoperative fill volumes >300 cm3 had 10 times higher odds of skin necrosis (OR, 10.66, P =0.010). Volumes >400 cm3 had 15 times higher odds of skin necrosis (OR, 15.56, P = 0.002). Mastectomy specimen weight was correlated with skin necrosis. Specimens >500 g had 10 times higher odds of necrosis and specimens >1000 g had 18 times higher odds of necrosis (OR, 10.03 and OR, 18.43; P =0.003 and P <0.001, respectively). Mastectomy skin necrosis was associated with a 50% increased inpatient charge. Conclusion: Mastectomy flap necrosis is associated with HTN, larger TE volumes and mastectomy specimen weights, resulting in increased inpatient charges. Conservative TE volumes should be considered for patients with hypertension and larger mastectomy specimens. PMID:26301139

  10. Carbendazim impends hepatic necrosis when combined with imazalil or cypermethrin.

    PubMed

    Dikić, Domagoj; Landeka, Irena; Knežević, Fabijan; Mojsović-Ćuić, Ana; Benković, Vesna; Horvat-Knežević, Anica; Lončar, Goran; Teparić, Renata; Rogić, Dunja

    2012-05-01

    Imazalil, cypermethrin and carbendazim are detected in plants for human nutrition. To explore whether their combinations, applied orally in low doses, would induce changes in metabolic patterns and hepatotoxicity, a subchronic in vivo experiment was conducted. Doses of 10mg/kg of imazalil (im) and cypermethrin (cy) and 20 mg/kg of carbendazim (car) and their combinations (im, 10 mg/kg+cy, 10mg/kg; im, 10mg/kg+car, 20mg/kg; car, 20 mg/kg + im, 10 mg/kg) were given to Swiss mice daily over 28 days. After 24 hr from the last dose, the relationships of cytotoxicity biomarkers were analysed: serum lactate dehydrogenase, aspartate transaminase, alanine transferase, amylase, alkaline phosphatase, creatine kinase, creatinine and total proteins. Individual pesticides showed different toxic potential (cy>im car) generally characterized by increase in enzyme activities. Histological analysis showed that cypermethrin, but not imazalil or carbendazim, alone can cause mild necrosis. Combinations generally caused decrease in the activity of enzymes, indicating liver damage. Low doses of carbendazim in combination with low doses of imazalil or cypermethrin caused very pronounced hepatic necrosis, more than any of the three individually applied pesticides or combination of imazalil and cypermethrin. In fruits and vegetables for human consumption, residues of these three pesticides and prolonged combined intake of low doses, which by themselves acutely would not cause any effect, may have similar hepatotoxic effects. PMID:22077925

  11. Predicting development of infected necrosis in acute necrotizing pancreatitis.

    PubMed

    Dambrauskas, Zilvinas; Pundzius, Juozas; Barauskas, Giedrius

    2006-01-01

    The incidence of severe acute pancreatitis is about 30 cases per 100,000 inhabitants, and it carries an overall mortality rate of 10-15%. Infection of pancreatic necrosis occurs in 20-30% of patients with severe acute pancreatitis and triples the mortality rate. Therefore, early prediction and diagnosis of infection in necrotizing pancreatitis are extremely important. The aim of the studies included in this review was to investigate the potential of specific prognostic factors to predict the development of secondary pancreatic infection in severe acute pancreatitis. This is seen as an important tool allowing to perform a computed tomography- or ultrasound-guided fine needle aspiration for bacteriological sampling at the right moment, to confirm the diagnosis, and, finally, to select the subgroup of patients who would benefit from the antibiotic prophylaxis. Precise patients' selection could possibly result in more rational use of antibiotics in patients with acute necrotizing pancreatitis and reduction of multi-resistant bacteria. Recent studies show that C-reactive protein is an important prognostic marker of pancreatic necrosis with the highest sensitivity and negative prognostic value in this respect. Procalcitonin alone or in combination with interleukin-6 best identifies patients not at risk for infection. However, a review of the clinical studies suggests that we still do not have an optimal model, thus there is a need for new more reliable biochemical and/or clinical predictive systems.

  12. Epidemiological characteristics of infectious hematopoietic necrosis virus (IHNV): a review.

    PubMed

    Dixon, Peter; Paley, Richard; Alegria-Moran, Raul; Oidtmann, Birgit

    2016-01-01

    Infectious hematopoietic necrosis virus (IHNV, Rhabdoviridae), is the causative agent of infectious hematopoietic necrosis (IHN), a disease notifiable to the World Organisation for Animal Health, and various countries and trading areas (including the European Union). IHNV is an economically important pathogen causing clinical disease and mortalities in a wide variety of salmonid species, including the main salmonid species produced in aquaculture, Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). We reviewed the scientific literature on IHNV on a range of topics, including geographic distribution; host range; conditions required for infection and clinical disease; minimum infectious dose; subclinical infection; shedding of virus by infected fish; transmission via eggs; diagnostic tests; pathogen load and survival of IHNV in host tissues. This information is required for a range of purposes including import risk assessments; parameterisation of disease models; for surveillance planning; and evaluation of the chances of eradication of the pathogen to name just a few. The review focuses on issues that are of relevance for the European context, but many of the data summarised have relevance to IHN globally. Examples for application of the information is presented and data gaps highlighted. PMID:27287024

  13. Molecular biology and immunology for clinicians 23: autoimmunity and the superfamilies of tumor necrosis factor and tumor necrosis factor receptor.

    PubMed

    Sigal, Leonard H

    2003-04-01

    The parsimony of nature can be stated as "if its not broke don't fix it, just tweak it and reuse it again and again." Nature recycles: once a motif is demonstrably useful it shows up again, often in unexpected places. Tumor necrosis factor and its receptor(s) are examples of this. At least 20 molecules have now been identified as being 25% homologous or more identical with tumor necrosis factor and being involved in a variety of immune and nonimmune functions. Members of the receptor superfamily have shared structural motifs and trigger shared intracellular signaling pathways. Rather than having been implicated in arcane and rare syndromes, some of these activities are pivotal in immune function and, when perturbed, some predispose to known immunodeficiency and autoimmune disease. Not surprisingly, some of these are becoming targets for immunomodulation. New members of these 2 superfamilies are currently being described and the newcomers and the "original stock" will show up in the clinic before you know it! Part of the confusion has always been that each laboratory describing a new biologic principle names the mediating compound. Thus, multiple labs, multiple names for the same protein (recall Ro/SS-A, La/SS-B). Thus, special attention is paid below to acronyms and their synonyms.

  14. Cloning, sequence, and expression of the glycoprotein gene of infectious hematopoietic necrosis virus, a fish rhabdovirus

    SciTech Connect

    Feyereisen-Koener, J.M.

    1987-01-01

    Double-stranded cDNA was prepared from infectious hematopoietic necrosis virus mRNA and cloned into the plasmid vector pUC8. A coprotein (G-protein) of infectious hematopoietic necrosis virus was selected by hybridization to a /sup 32/P-labeled probe. The restriction map and nucleotide sequence of the mRNA encoding the glycoprotein of infectious hematopoietic necrosis virus was determined using this full-length cDNA clone.

  15. Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

    PubMed

    Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

    2011-03-01

    The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma. PMID:21214410

  16. Characterization of necrosis-inducing NLP proteins in Phytophthora capsici

    PubMed Central

    2014-01-01

    Background Effector proteins function not only as toxins to induce plant cell death, but also enable pathogens to suppress or evade plant defense responses. NLP-like proteins are considered to be effector proteins, and they have been isolated from bacteria, fungi, and oomycete plant pathogens. There is increasing evidence that NLPs have the ability to induce cell death and ethylene accumulation in plants. Results We evaluated the expression patterns of 11 targeted PcNLP genes by qRT-PCR at different time points after infection by P. capsici. Several PcNLP genes were strongly expressed at the early stages in the infection process, but the expression of other PcNLP genes gradually increased to a maximum at late stages of infection. The genes PcNLP2, PcNLP6 and PcNLP14 showed the highest expression levels during infection by P. capsici. The necrosis-inducing activity of all targeted PcNLP genes was evaluated using heterologous expression by PVX agroinfection of Capsicum annuum and Nicotiana benthamiana and by Western blot analysis. The members of the PcNLP family can induce chlorosis or necrosis during infection of pepper and tobacco leaves, but the chlorotic or necrotic response caused by PcNLP genes was stronger in pepper leaves than in tobacco leaves. Moreover, PcNLP2, PcNLP6, and PcNLP14 caused the largest chlorotic or necrotic areas in both host plants, indicating that these three genes contribute to strong virulence during infection by P. capsici. This was confirmed through functional evaluation of their silenced transformants. In addition, we further verified that four conserved residues are putatively active sites in PcNLP1 by site-directed mutagenesis. Conclusions Each targeted PcNLP gene affects cells or tissues differently depending upon the stage of infection. Most PcNLP genes could trigger necrotic or chlorotic responses when expressed in the host C. annuum and the non-host N. benthamiana. Individual PcNLP genes have different phytotoxic effects, and Pc

  17. Ischaemic necrosis of the tongue as a rare complication of cardiogenic shock.

    PubMed

    Hulstaert, E; Roggeman, E; Beeckman, A-S; Moerman, M; Vanderstraeten, E; Rasquin, K; Monsaert, E; Baert, D; Dewint, P; Burvenich, P; Van Steenkiste, C

    2015-12-01

    Ischaemic necrosis of the tongue is an unusual clinical finding. In most cases it is associated with vasculitis, particularly giant cell arteritis (GCA). Other causes include profound cardiogenic shock. We report a case of tongue necrosis in an 81-year-old Caucasian woman. The patient was admitted to the intensive care unit (ICU) for cardiogenic shock. Swelling of the tongue was reported before intubation and evolved into tongue ischaemia and necrosis of the tip of the tongue. After surgical debridement the patient recovered. To our knowledge, this is the second report of a patient surviving tongue necrosis resulting from cardiogenic shock.

  18. Gallbladder torsion with acute cholecystitis and gross necrosis.

    PubMed

    Alkhalili, Eyas; Bencsath, Kalman

    2014-01-01

    A 92-year-old woman presented to the emergency department with a 2-week history of worsening right-sided abdominal pain. On examination she had right mid-abdominal tenderness. Laboratory studies demonstrated leukocytosis with normal liver function tests. A CT of the abdomen was remarkable for a large fluid collection in the right abdomen and no discernible gallbladder in the gallbladder fossa. An ultrasound confirmed the suspicion of a distended, floating gallbladder. The patient was taken to the operating room for laparoscopic cholecystectomy. The gallbladder was found to have volvulised in a counter -clockwise manner around its pedicle, with gross necrosis of the gallbladder. She underwent laparoscopic cholecystectomy. Pathological examination revealed acute necrotising calculus cholecystitis.

  19. Tumor necrosis factor-alpha antagonist-induced sarcoidosis.

    PubMed

    Clementine, Rochelle Robicheaux; Lyman, Justin; Zakem, Jerald; Mallepalli, Jyothi; Lindsey, Stephen; Quinet, Robert

    2010-09-01

    Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Tumor necrosis factor (TNF)-alpha is an important player in granuloma formation, and recent clinical trials have investigated the efficacy of TNF-alpha inhibitors in sarcoidosis. Paradoxically, there are several case reports in the medical literature describing the development of sarcoidosis in patients treated with TNF-alpha inhibitors. We describe 3 cases of TNF-alpha antagonist-induced sarcoidosis: 1 case of pulmonary, ocular and cutaneous sarcoidosis developing in a patient receiving infliximab for erosive rheumatoid arthritis, 1 case of etanercept-induced sarcoidosis in a patient with seronegative rheumatoid arthritis, and 1 case of sarcoidosis developing in a patient receiving etanercept for erosive rheumatoid arthritis. We also provide a brief discussion on the role of TNF alpha in granuloma formation and implications in the use of TNF-alpha antagonists in autoimmune disease.

  20. [Fatal hepatic necrosis during treatment with sodium valproate].

    PubMed

    Miguil, M; Chlihi, A; Mjahed, K; Sarf, I; Moutawakkil, S; Benaguida, M

    1995-01-01

    The authors report a case of fatal hepatic failure in a 19-year old young man suffering from absence seizures and treated for two months with valproic acid (VPA). The duration of VPA therapy before onset of clinical manifestations was four weeks. The prodromal symptoms were weakness, anorexia, and vomiting, then in a few weeks occurred a jaundice and an hepatic encephalopathy leading to death. Among laboratory findings disturbance of liver tests and particularly depressed levels of clotting factors were observed. The histologic study of the liver showed an extended centrolobular necrosis associated with fatty change and fibrosis. The mechanism of this hepatic failure remains unknown. The seriousness of this complication necessitates to respect any contraindications.

  1. Progressive outer retinal necrosis in immunocompromised kidney allograft recipient.

    PubMed

    Turno-Kręcicka, A; Boratyńska, M; Tomczyk-Socha, M; Mazanowska, O

    2015-06-01

    Ocular complications in patients who underwent renal transplantation are attributed to side effects of the immunosuppressive regimen. Progressive outer retinal necrosis (PORN) syndrome is a clinical variant of necrotizing herpetic retinopathy and it occurs almost exclusively in patients with acquired immunodeficiency syndrome. We present a case of a human immunodeficiency virus-negative patient who underwent renal transplant and, after a few years, developed bilateral PORN associated with viral infections. Varicella zoster virus (VZV) and BK virus were identified by polymerase chain reaction from the vitreous fluid. It is unclear which of the viruses identified had the dominant role in the pathogenesis of PORN and other organ damage, or whether their actions were synergistic. Adequate antiviral immune surveillance, as well as pre-transplant vaccination against VZV, may reduce the incidence of VZV infection and its complications. PMID:25846017

  2. Programmed necrosis in inflammation: Toward identification of the effector molecules.

    PubMed

    Wallach, David; Kang, Tae-Bong; Dillon, Christopher P; Green, Douglas R

    2016-04-01

    Until recently, programmed cell death was conceived of as a single set of molecular pathways. We now know of several distinct sets of death-inducing mechanisms that lead to differing cell-death processes. In one of them--apoptosis--the dying cell affects others minimally. In contrast, programmed necrotic cell death causes release of immunostimulatory intracellular components after cell-membrane rupture. Defining the in vivo relevance of necrotic death is hampered because the molecules initiating it [such as receptor-interacting protein kinase-1 (RIPK1), RIPK3, or caspase-1] also serve other functions. Proteins that participate in late events in two forms of programmed necrosis [mixed lineage kinase domain-like protein (MLKL) in necroptosis and gasdermin-D in pyroptosis] were recently discovered, bringing us closer to identifying molecules that strictly serve in death mediation, thereby providing probes for better assessing its role in inflammation.

  3. Antiviral selection in the management of acute retinal necrosis

    PubMed Central

    Tam, Patrick MK; Hooper, Claire Y; Lightman, Susan

    2010-01-01

    There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised. PMID:20169044

  4. Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy.

    PubMed

    Schaer, David A; Hirschhorn-Cymerman, Daniel; Wolchok, Jedd D

    2014-01-01

    With the success of ipilimumab and promise of programmed death-1 pathway-targeted agents, the field of tumor immunotherapy is expanding rapidly. Newer targets for clinical development include select members of the tumor necrosis factor receptor (TNFR) family. Agonist antibodies to these co-stimulatory molecules target both T and B cells, modulating T-cell activation and enhancing immune responses. In vitro and in vivo preclinical data have provided the basis for continued development of 4-1BB, OX40, glucocorticoid-induced TNFR-related gene, herpes virus entry mediator, and CD27 as potential therapies for patients with cancer. In this review, we summarize the immune response to tumors, consider preclinical and early clinical data on select TNFR family members, discuss potential translational challenges and suggest possible combination therapies with the aim of inducing durable antitumor responses. PMID:24855562

  5. Malaria: a tumour necrosis factor inhibitor from parasitized erythrocytes.

    PubMed Central

    Sheikh, N A; Caro, H N; Taverne, J; Playfair, J H; Rademacher, T W

    1996-01-01

    The excessive production of tumour necrosis factor (TNF) is associated with the pathology of blood-stage malaria and phosphatidylinositol-containing phospholipid antigens from parasitized erythrocytes stimulate its secretion by macrophages, thus acting as toxins. This brief report describes some properties of an inhibitor present in lysates from erythrocytes infected with malarial parasites that blocked the detection of recombinant TNF in an enzyme-linked immunosorbent assay and diminished or abolished the cytotoxicity of TNF. It was not found in control lysates of normal erythrocytes. Its addition to macrophage cultures stimulated by toxic malarial preparations or by bacterial lipopolysaccharide also blocked the detection of TNF. These findings may explain the contradictory results obtained from different assays for TNF, and emphasize the need for caution when interpreting the results of a single assay system. If released when parasitized erythrocytes rupture in vivo, the inhibitor could help protect both parasite and host from the damaging effects of TNF. PMID:8778034

  6. Laser-induced fluorescence spectroscopy in tissue local necrosis detection

    NASA Astrophysics Data System (ADS)

    Cip, Ondrej; Buchta, Zdenek; Lesundak, Adam; Randula, Antonin; Mikel, Bretislav; Lazar, Josef; Veverkova, Lenka

    2014-03-01

    The recent effort leads to reliable imaging techniques which can help to a surgeon during operations. The fluorescence spectroscopy was selected as very useful online in vivo imaging method to organics and biological materials analysis. The presented work scopes to a laser induced fluorescence spectroscopy technique to detect tissue local necrosis in small intestine surgery. In first experiments, we tested tissue auto-fluorescence technique but a signal-to-noise ratio didn't express significant results. Then we applied a contrast dye - IndoCyanine Green (ICG) which absorbs and emits wavelengths in the near IR. We arranged the pilot experimental setup based on highly coherent extended cavity diode laser (ECDL) used for stimulating of some critical areas of the small intestine tissue with injected ICG dye. We demonstrated the distribution of the ICG exciter with the first file of shots of small intestine tissue of a rabbit that was captured by high sensitivity fluorescent cam.

  7. Progressive outer retinal necrosis in immunocompromised kidney allograft recipient.

    PubMed

    Turno-Kręcicka, A; Boratyńska, M; Tomczyk-Socha, M; Mazanowska, O

    2015-06-01

    Ocular complications in patients who underwent renal transplantation are attributed to side effects of the immunosuppressive regimen. Progressive outer retinal necrosis (PORN) syndrome is a clinical variant of necrotizing herpetic retinopathy and it occurs almost exclusively in patients with acquired immunodeficiency syndrome. We present a case of a human immunodeficiency virus-negative patient who underwent renal transplant and, after a few years, developed bilateral PORN associated with viral infections. Varicella zoster virus (VZV) and BK virus were identified by polymerase chain reaction from the vitreous fluid. It is unclear which of the viruses identified had the dominant role in the pathogenesis of PORN and other organ damage, or whether their actions were synergistic. Adequate antiviral immune surveillance, as well as pre-transplant vaccination against VZV, may reduce the incidence of VZV infection and its complications.

  8. Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil.

    PubMed

    Israel, Y; Kalant, H; Orrego, H; Khanna, J M; Videla, L; Phillips, J M

    1975-03-01

    We have previously reported that a hypermetabolic state, resembling that produced by thryoid hormones, exists in the livers of animals treated chronically with ethanol. We propose that this alteration produces a relative hypoxia in the centrilobular zone of the liver which, if severe enough, leads to cellular death and to the production of hepatitis. Rats consuming ethanol for 30 days, given with a nutritionally adequate diet, and exposed to reduced oxygen tensions for only 6 hr, developed histological and biochemical evidence of hepatocellular necrosis and inflammatory lesions confined to the centrilobular zone. The severity was proportional to the degree of hypoxia. Pair-fed (nonalcohol) controls showed no such lesions. Treatment of the animals with propylthiouracil for 3-10 days abolished the hypermetabolic state of the liver in ethanol-consuming animals, and drastically reduced the histological and biochemical effects of hypoxia in them. These findings may have implications for pathogenesis and treatment of alcoholic hepatitis in man.

  9. Phylogeography of infectious haematopoietic necrosis virus in North America

    USGS Publications Warehouse

    Kurath, Gael; Garver, Kyle A.; Troyer, Ryan M.; Emmenegger, Eveline J.; Einer-Jensen, Katja; Anderson, Eric D.

    2003-01-01

    Infectious hematopoietic necrosis virus (IHNV) is a rhabdoviral pathogen that infects wild and cultured salmonid fish throughout the Pacific Northwest of North America. IHNV causes severe epidemics in young fish and can cause disease or occur asymptomatically in adults. In a broad survey of 323 IHNV field isolates, sequence analysis of a 303 nucleotide variable region within the glycoprotein gene revealed a maximum nucleotide diversity of 8.6 %, indicating low genetic diversity overall for this virus. Phylogenetic analysis revealed three major virus genogroups, designated U, M and L, which varied in topography and geographical range. Intragenogroup genetic diversity measures indicated that the M genogroup had three- to fourfold more diversity than the other genogroups and suggested relatively rapid evolution of the M genogroup and stasis within the U genogroup. We speculate that factors influencing IHNV evolution may have included ocean migration ranges of their salmonid host populations and anthropogenic effects associated with fish culture.

  10. Some aspects of pathogenesis of infectious hematopoietic necrosis (IHN)

    USGS Publications Warehouse

    Yasutake, William T.; Amend, Donald F.

    1972-01-01

    The histopathogenesis of infectious haematopoietic necrosis (IHN) virus infection was studied by exposing juvenile sockeye salmon (Oncorhynchus nerka) to the IHN virus. Fish samples were taken every 24 h for histological examination and for determination of virus concentration. A close correlation was found between histopathological changes and virus concentration. The most significant changes occurred 4 days after exposure. The haematopocitic tissue of the kidney was the most extensively involved but minor degenerative changes were seen in the liver, pancreas, and in the granular cells of the digestive tract. On the 4th day, maximum tissue concentration of virus was reached and the mortality increased. By the 5th day, 90% of the samples showed extensive pathological changes in the kidney, together with variable changes in spleen, liver, pancreas, and gut. Similarities in the histopathogenesis of IHN, Oregon sockeye disease (OSD), Sacramento River chinook disease (SRCD) and viral haemorrhagic septicaemia (VHS), are discussed.

  11. Progressive outer retinal necrosis in a patient with nephrotic syndrome.

    PubMed

    Shinoda, K; Inoue, M; Ishida, S; Kawashima, S; Wakabayashi, T; Suzuki, S; Katsura, H

    2001-01-01

    Progressive outer retinal necrosis syndrome (PORN) is a variant of necrotizing herpetic retinopathy and the majority of the described cases were related to acquired immunodeficiency syndrome. We present a patient who is HIV negative with nephrotic syndrome and prednisolone use for 4 months who showed clinical features of PORN. Low CD4 counts and lymphocytopenia suggested immunosuppression. In the left eye, tractional retinal detachment at the posterior pole followed by incomplete posterior vitreous detachment developed. In addition to intravenous administration of acyclovir, vitreous surgeries including stripping of the posterior hyaloid and silicone-oil tamponade were successfully performed to repair the retinal detachment in the left eye and to prevent it in the right eye.

  12. Tumor necrosis factor alpha polymorphism in heart failure/cardiomyopathy.

    PubMed

    Vadlamani, Lou; Iyengar, Srinivas

    2004-01-01

    Tumor necrosis factor a (TNF-alpha) is a proinflammatory cytokine that is produced by activated macrophages. It has been shown to stimulate the release of endothelial cytokines and NO, increase vascular permeability, decrease contractility, and induce a prothrombotic state. The most studied TNF-a gene mutation in heart disease is a gamma to alpha substitution, which occurs when 308 nucleotides move upstream from the transcription initiation site in the TNF promoter and has been associated with elevated levels of TNF-alpha. The TNF1 allele (wild type) contains gamma at this site, while the TNF2 allele has an alpha substitution at the site. The TNF2 allele is a more powerful transcriptional activator, therefore leading to higher TNF-alpha levels. Most of the studies to date have failed to conclusively show any link between the polymorphism and heart disease, both coronary artery disease and cardiomyopathy/heart failure. PMID:15591843

  13. Polypeptide composition of spleen necrosis virus, a reticuloendotheliosis virus.

    PubMed Central

    Mosser, A G

    1975-01-01

    The polypeptide composition of virions of spleen necrosis virus, a reticuloendotheliosis virus, was determined using electrophoresis on sodium dodecyl sulfate-containing, 10 percent polyacrylamide gels. Ten polypeptides were resolved. Four of these were present in minor and somewhat variable amounts. Two proteins, gp71 and gp22, contained D-glucosamine and were located on the outer surface of the lipid envelope, as demonstrated by lactoperoxidase-catalyzed iodination and by bromelain digestion. The results suggest that two of the minor proteins, p36 and p26, were also located on the outer surface, although they lacked D-glucosamine. Treatment of the virus with 0.25 percent Nonidet P-40 and 1 percent dithiothreitol produced a subparticle with a buoyant density of approximately 1.31 g/cm-3. This particle was relatively enriched with polypeptides p77, p62, and p50 and contained small amounts of three other polypeptides. PMID:1142473

  14. [A case of nasal tip necrosis after hyaluronic acid injection].

    PubMed

    Honart, J-F; Duron, J-B; Mazouz Dorval, S; Rausky, J; Revol, M

    2013-12-01

    Hyaluronic acid (HA) is the most used dermal filler. Some complications associated with its use have been described, but most of them are rare and benign. We report an exceptional case of skin necrosis of the tip of the nose, in a 22-year-old patient, after HA injection. The initial appearance may occurred subsequent aesthetic sequels. After necrotic tissue excision, patient was followed in rapid succession. Daily local care has led to wound healing, without any important sequel. This rare complication reminds us that HA injections are not without risk, despite their apparent simplicity of use. Moreover, the case presented confirms the potential healing of the nasal tip, allowing treatment with wound healing, rather than other early invasive procedure.

  15. Role of Tumor Necrosis Factor Superfamily in Neuroinflammation and Autoimmunity.

    PubMed

    Sonar, Sandip; Lal, Girdhari

    2015-01-01

    Tumor necrosis factor superfamily (TNFSF) molecules play an important role in the activation, proliferation, differentiation, and migration of immune cells into the central nervous system (CNS). Several TNF superfamily molecules are known to control alloimmunity, autoimmunity, and immunity. Development of transgenic and gene knockout animals, and monoclonal antibodies against TNFSF molecules have increased our understanding of individual receptor-ligand interactions, and their intracellular signaling during homeostasis and neuroinflammation. A strong clinical association has been observed between TNFSF members and CNS autoimmunity such as multiple sclerosis and also in its animal model experimental autoimmune encephalomyelitis. Therefore, they are promising targets for alternative therapeutic options to control autoimmunity. Although, TNFSF ligands are widely distributed and have diverse functions, we have restricted the discussions in this review to TNFSF receptor-ligand interactions and their role in the pathogenesis of neuroinflammation and CNS autoimmunity.

  16. Avascular Necrosis of the Femoral Head: Are Any Genes Involved?

    PubMed Central

    Pouya, Farzaneh; Kerachian, Mohammad Amin

    2015-01-01

    Avascular necrosis of the femoral head (ANFH) is a pathologic process that results from interruption of blood supply to the femur bone resulting in the death of bone cells and collapse of the femoral head. Nontraumatic ANFH continues to be a significant challenge to orthopedic surgeons. While the exact mechanisms remain elusive, many new insights have emerged from research in the last decade that has given us a clearer picture of the pathogenesis of nontraumatic ANFH. Progression to the end stage of ANFH appears to be related to five main mechanisms: hypercoagulable conditions, angiogenesis suppressions, hyperadipogenesis, heritable states, and switching the bone remodelling into bone resorption. Researchers have been examining the pathogenic mechanisms of ANFH but none of these theories have been firmly confirmed although some appear more plausible than the others. All of these factors can switch bone remodelling into bone resorption, which can further lead to ANFH progression ending up to femoral head collapse. PMID:26213697

  17. Bone marrow necrosis in acute leukemia: Clinical characteristic and outcome.

    PubMed

    Badar, Talha; Shetty, Aditya; Bueso-Ramos, Carlos; Cortes, Jorge; Konopleva, Marina; Borthakur, Gautam; Pierce, Sherry; Huang, Xuelin; Chen, Hsiang-Chun; Kadia, Tapan; Daver, Naval; Dinardo, Courtney; O'Brien, Susan; Garcia-Manero, Guillermo; Kantarjian, Hagop; Ravandi, Farhad

    2015-09-01

    Bone marrow necrosis (BMN) is characterized by infarction of the medullary stroma, leading to marrow necrosis with preserved cortical bone. In reported small series, BMN in hematological malignancies is associated with poor prognosis. We sought to find the impact of BMN on clinical outcome in a relatively larger cohort of patients with acute leukemias. Overall we evaluated 1,691 patients; 1,051 with acute myeloid leukemia (AML) and 640 with acute lymphocytic leukemia referred to our institution between 2002 and 2013. Patients with AML and acute lymphoblastic leukemia (ALL) were evaluated separately to determine the incidence of BMN, associated clinical features and its prognostic significance. At initial diagnosis, BMN was observed in 25 (2.4%) patients with AML and 20 (3.2%) patients with ALL. In AML, BMN was significantly associated with French-American-British AML M5 morphology (32% vs. 10%, P = 0.002). The complete remission (CR) rate in AML with and without BMN was 32% and 59% respectively (P = 0.008). Likewise, CR rate in ALL with BMN was also inferior, 70% vs. 92% (P = 0.005). The median overall survival (OS) in AML with BMN was significantly poorer, 3.7 months compared to 14 months without BMN (P = 0.003). Similarly, the median OS in ALL with and without BMN was 61.7 and 72 months respectively (P = 0.33). BMN is not a rare entity in AML and ALL, but is infrequent. BMN in AML and in ALL is suggestive of inferior response and poor prognosis.

  18. Fat Necrosis of the Breast Following Folinic Acid Extravasation

    PubMed Central

    Hammon, M.; Dilbat, G.; Schulz-Wendtland, R.

    2013-01-01

    Case Report: We report here on a 58-year-old patient with abnormal findings in the left breast on screening mammography (October 2012). In May 2008 the patient was diagnosed with rectal cancer, subsequently treated by surgical resection followed by radiochemotherapy. In September 2011 the patient was diagnosed with peritoneal cancer. Extravasation of folinic acid occurred during palliative chemotherapy, which was delivered through a surgically implanted port, placed prepectorally on the left side. The patient had not previously undergone breast surgery. The abnormal finding in the left breast was located at the 1–2 oʼclock position. The mammogram showed extensive hyperdense nodules with predominantly round, fine granular calcifications. On sonography, the findings presented as a hypoechogenic, inhomogenous, partially diffuse, partly solid, partly cystic mass with individual calcifications and reduced echogenicity in the dorsal aspect. Strong densification of the left breast was found at the corresponding position on palpation. On computed tomography (CT) done during follow-up for rectal cancer, new streaky/pitted densifications were noted in the left breast. Based on the patientʼs previous history and the results of the breast diagnostics a diagnosis of extensive fat necrosis after folinic acid extravasation was made. No further measures were taken. The patient will continue to be screened using mammography. Conclusion: A good knowledge of the mammographic and sonographic features of fat necrosis can reduce the number of unnecessary biopsies. Careful consideration of the patientʼs prior medical history is very important in breast diagnostics and may often be decisive for the correct diagnosis. PMID:24771912

  19. Tumour necrosis factor-alpha induces translocation of protein kinase C in tumour necrosis factor-sensitive cell lines.

    PubMed Central

    Matsubara, N; Fuchimoto, S; Orita, K

    1991-01-01

    In this study we investigated whether the anti-proliferative effect of tumour necrosis factor-alpha (TNF-alpha) was associated with the activation of protein kinase C (PKC), using PANC-1 cells (TNF-alpha sensitive) and LoVo cells (TNF-alpha resistant). In combination with 12-0-tetradecanoylphorbol-13-acetate (TPA), a potent activator of PKC, TNF-alpha caused marked inhibition of the growth of LoVo cells. Inhibition of PANC-1 cell growth by TNF-alpha was blocked by pretreatment with TPA for 24 hr, along with down-regulation of PKC activity. Intracellular translocation of PKC from cytosol to membrane was induced by TNF-alpha treatment in PANC-1 cells but not in LoVo cells. PMID:1916896

  20. Nasal Skin Necrosis: An Unexpected New Finding in Severe Chikungunya Fever.

    PubMed

    Torres, Jaime R; Córdova, Leopoldo G; Saravia, Víctor; Arvelaez, Joanne; Castro, Julio S

    2016-01-01

    Three adult Venezuelan patients with virologically confirmed Chikungunya fever, who developed extensive acute nasal skin necrosis early in the course of a life-threatening illness characterized by shock and multiple organ dysfunction syndrome, are discussed. One patient survived and fully recovered. Nasal necrosis has not previously been associated with the disease.

  1. Analysis of risk and predictors of brain radiation necrosis after radiosurgery.

    PubMed

    Zhuang, Hongqing; Zheng, Yi; Wang, Junjie; Chang, Joe Y; Wang, Xiaoguang; Yuan, Zhiyong; Wang, Ping

    2016-02-16

    In this study, we examined the factors contributing to brain radiation necrosis and its predictors of patients treated with Cyberknife radiosurgery. A total of 94 patients with primary or metastatic brain tumours having been treated with Cyberknife radiotherapy from Sep. 2006 to Oct. 2011 were collected and retrospectively analyzed. Skull based tracking was used to deliver radiation to 104 target sites. and the prescribed radiation doses ranged from 1200 to 4500 cGy in 1 to 8 fractions with a 60% to 87% isodose line. Radiation necrosis was confirmed by imaging or pathological examination. Associations between cerebral radiation necrosis and factors including diabetes, cardio-cerebrovascular disease, target volume, isodose line, prescribed dosage, number of fractions, combination with whole brain radiation and biologically equivalent dose (BED) were determined by logistic regression. ROC curves were created to measure the predictive accuracy of influence factors and identify the threshold for brain radiation necrosis. Our results showed that radiation necrosis occurred in 12 targets (11.54%). Brain radiation necrosis was associated by BED, combination with whole brain radiotherapy, and fractions (areas under the ROC curves = 0.892±0.0335, 0.650±0.0717, and 0.712±0.0637 respectively). Among these factors, only BED had the capability to predict brain radiation necrosis, and the threshold dose was 7410 cGy. In conclusion, BED is the most effective predictor of brain radiation necrosis, with a dose of 7410 cGy being identified as the threshold.

  2. Bladder Necrosis Associated with Placenta Accreta, Embolization, and Repair of Cystotomies

    PubMed Central

    Wu, Wayland J.; Smith, Arthur D.

    2015-01-01

    Abstract Bladder necrosis is an unusual and potentially devastating complication of embolization of the hypogastric arterial branches. The rich collateral blood supply makes this an extremely rare event. We present the case of a patient with bladder necrosis following placenta accreta that was treated with total abdominal hysterectomy and uterine artery embolization and cystotomy repairs. PMID:27579379

  3. [Progress on tantalum rod implanting for the treatment of femur head necrosis].

    PubMed

    Tang, Xiao-kang; Ye, Fu-sheng; Tong, Pei-jian; Fan, Yan-hua; Li, Min; Ying, Hang; Xiao, Lu-wei

    2013-07-01

    Incorrect treatment for femur head necrosis can cause collapse of femoral head and tresult in severe harm for the patients (especially for the patient with middle-aged and young). The structure and mechanics characteristics of tantalum rod is similar to bone tissue, it higher strength and can adapt the internal environment of organism, so it has a large potency in treating femur head necrosis. Treatment of early femur head necrosis with tantalum rod implanting had alreadly widey applied at home and abroad, the method has the advantages of simple operation, little risk, less complication and beseems the patient with stage I - II of ARCO. But reasons that the difficult diagnosis of early femur head necrosis, localized effect of tantalum rod, different experience of medical worker,caused the contentions about effect of tantalum rod implanting. With development of science, tantalum rod implanting combined with correlative biotechnology should raise the effect in treating femur head necrosis.

  4. [Brachial plexus compression from supraclavicular encapsulated fat necrosis. A case report].

    PubMed

    Domínguez-Páez, Miguel; de Miguel-Pueyo, Luis; Marín-Salido, Esteban José; Carrasco-Brenes, Antonio; Martín-Gallego, Alvaro; Arráez-Sánchez, Miguel Ángel

    2014-01-01

    We report the case of a 44-year-old male, lacking clinical history of previous illness, who had surgery at our hospital to treat a mass in the supraclavicular space. The patient presented with a 1-month progressive distal paresis of the left arm. The histo-pathological examination of the mass revealed an encapsulated fat necrosis. Fat necrosis is characterised by cystic architecture, encapsulation with fat necrosis within, and inflammatory infiltration of its walls. Neural structure compression secondary to this tumour mass is very rare. Fat necrosis is more frequent in the lower limbs, in areas exposed to trauma. This article is the first report of brachial plexus compression due to supraclavicular fat necrosis. PMID:24837841

  5. Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies

    SciTech Connect

    Di Chiro, G.; Oldfield, E.; Wright, D.C.; De Michele, D.; Katz, D.A.; Patronas, N.J.; Doppman, J.L.; Larson, S.M.; Ito, M.; Kufta, C.V.

    1988-01-01

    Cerebral necrosis after radiotherapy for brain tumors is being recognized as a problem more common than previously estimated. Distinction between this iatrogenic complication and tumor recurrence cannot be made by either CT or MR imaging. By using positron emission tomography (PET) with /sup 18/F-deoxyglucose (FDG) we were able to reach a diagnosis of radiation necrosis, later verified, in 10 of 95 patients referred for the purpose of differentiating tumor recurrence from necrosis. The critical PET-FDG feature was focal hypometabolism in the area of necrosis, which contrasted with the hypermetabolism associated with the residual/recurrent tumor. In addition, four cases of cerebral necrosis after supraophthalmic, intraarterial chemotherapy (BCNU) were studied with the PET-FDG method. The area of chemotherapy damage was also characterized by marked hypometabolism. Histology revealed both similarities and differences between radio- and chemonecrosis.

  6. Spontaneous and bilateral necrosis of the femoral head in a young experimental beagle dog.

    PubMed

    Kobayashi, Ryosuke; Kurotaki, Tetsuro; Yamada, Naoaki; Kumabe, Shino; Doi, Takuya; Wako, Yumi; Tsuchitani, Minoru

    2015-04-01

    This report describes the pathological characterizations of a rare case of necrosis of the femoral head that was spontaneous, bilateral, avascular and nontraumatic. A 14-month-old beagle dog was presented with pain in the hind limbs. At necropsy, the articular surface in the bilateral femoral head was markedly irregular. There were no gross abnormalities other than in the hip joints. Microscopically, a wide range of trabecular bone necrosis localized in the subchondral area was observed in both femoral heads. In the right femoral head, fibrosis and proliferative vessels were noted in the subchondral area. The articular cartilage was thickened irregularly, but there was no evidence of cartilage necrosis. The bone marrow adjacent to the affected area showed severe depression. In the metaphysis, atrophic bone marrow, but not bone necrosis, was observed. This was a rare case of spontaneous necrosis of the femoral head in an experimental beagle dog. PMID:26028821

  7. Spontaneous and bilateral necrosis of the femoral head in a young experimental beagle dog

    PubMed Central

    Kobayashi, Ryosuke; Kurotaki, Tetsuro; Yamada, Naoaki; Kumabe, Shino; Doi, Takuya; Wako, Yumi; Tsuchitani, Minoru

    2015-01-01

    This report describes the pathological characterizations of a rare case of necrosis of the femoral head that was spontaneous, bilateral, avascular and nontraumatic. A 14-month-old beagle dog was presented with pain in the hind limbs. At necropsy, the articular surface in the bilateral femoral head was markedly irregular. There were no gross abnormalities other than in the hip joints. Microscopically, a wide range of trabecular bone necrosis localized in the subchondral area was observed in both femoral heads. In the right femoral head, fibrosis and proliferative vessels were noted in the subchondral area. The articular cartilage was thickened irregularly, but there was no evidence of cartilage necrosis. The bone marrow adjacent to the affected area showed severe depression. In the metaphysis, atrophic bone marrow, but not bone necrosis, was observed. This was a rare case of spontaneous necrosis of the femoral head in an experimental beagle dog. PMID:26028821

  8. Membrane Tumor Necrosis Factor Confers Partial Protection to Listeria Infection

    PubMed Central

    Torres, David; Janot, Laure; Quesniaux, Valerie F.J.; Grivennikov, Sergei I.; Maillet, Isabelle; Sedgwick, Jonathon D.; Ryffel, Bernhard; Erard, Francois

    2005-01-01

    Tumor necrosis factor (TNF) plays a critical role in the host response to the intracellular pathogen Listeria monocytogenes (LM). TNF exists in soluble and membrane-bound forms and exhibits both unique and overlapping activities. We examined the role of membrane TNF in the absence of secreted TNF for host resistance in knockin mice in which the endogenous TNF was replaced by a regulated, noncleavable allele (mem-TNF). Macrophages expressing mem-TNF produced nitric oxide and displayed normal bactericidal activity. Although mice completely deficient in TNF (TNF−/−) succumbed to LM infection within 4 days, mem-TNF mice controlled LM infection at a low dose (104 CFU) but succumbed at a higher dose of infection (105 CFU). In contrast to complete TNF deficiency, mem-TNF mice developed confined microabscesses that expressed inducible nitric oxide synthase. The transfer of lymphocytes from immunized mem-TNF, but not TNF−/−, mice protected TNF−/− mice from fatal infection. Taken together the data suggest that in the absence of soluble TNF, the presence of membrane-expressed TNF on phagocytes and lymphocytes partially restores host defense to LM infection. PMID:16314479

  9. Renal Papillary Necrosis Appearing as Bladder Cancer on Imaging.

    PubMed

    Dagrosa, Lawrence M; Ghali, Fady; Gormley, Elizabeth Ann

    2016-01-01

    A 79-year-old woman with a history of diabetes mellitus and recurrent urinary tract infections (UTIs) presented with acute onset left lower quadrant pain, left-sided back pain, vomiting, and dysuria. Abdominopelvic CT scan revealed left hydroureteronephrosis to the level of the left ureterovesical junction (UVJ) where a bladder mass appeared to be obstructing the left ureteral orifice. The obstruction was ultimately found to be the result of a sloughed renal papilla lodged in the distal ureter, which created an inflammatory mass at the UVJ. Her history of diabetes and frequent UTIs likely predisposed her to the development of renal papillary necrosis (RPN) that resulted in sloughing of a renal papilla, distal ureteral obstruction with subsequent bladder inflammation that mimicked a bladder mass on imaging. RPN is a condition associated with many etiologies and likely represents a common final pathway of several diseases. Although several hypotheses exist, it is primarily thought to be ischemic in nature and is related to the underlying physiology of the renal papillae. We present a case of hydroureteronephrosis and bladder mass secondary to a sloughed renal papilla from RPN. PMID:27579408

  10. Modulation of topoisomerase activities by tumor necrosis factor.

    PubMed

    Baloch, Z; Cohen, S; Fresa, K; Coffman, F D

    1995-01-01

    A number of chemotherapeutic agents which inhibit the DNA topoisomerases markedly potentiate cell death mediated by tumor necrosis factor, suggesting a role for these enzymes in the TNF cytotoxic mechanism. To investigate this possibility, topoisomerase I and II activities were assayed following TNF addition to murine L929 cells. Topoisomerase I and II activities increased within 15 min of TNF addition and returned to baseline levels within 1 and 2 hr, respectively. The increases in both topoisomerase activities were blocked by H-7 (but not H-8) and similar increases were seen following PMA addition. However, concentrations of H-7 which blocked the increased topoisomerase activities had no effect on TNF cytotoxicity nor on the enhancement of TNF cytotoxicity by topoisomerase inhibitors. Thus, in these cells topoisomerase activities are directly modified by TNF during the initial phases of a cytotoxic response. However, neither TNF cytotoxicity nor the enhancement of TNF cytotoxicity by topoisomerase inhibitors appears to require the TNF-mediated increases in topoisomerase activities. PMID:7842491

  11. Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis.

    PubMed

    Seike, Soshi; Miyamoto, Kazuaki; Kobayashi, Keiko; Takehara, Masaya; Nagahama, Masahiro

    2016-01-01

    Clostridium perfringens delta-toxin is a β-pore-forming toxin and a putative pathogenic agent of C. perfringens types B and C. However, the mechanism of cytotoxicity of delta-toxin remains unclear. Here, we investigated the mechanisms of cell death induced by delta-toxin in five cell lines (A549, A431, MDCK, Vero, and Caco-2). All cell lines were susceptible to delta-toxin. The toxin caused rapid ATP depletion and swelling of the cells. Delta-toxin bound and formed oligomers predominantly in plasma membrane lipid rafts. Destruction of the lipid rafts with methyl β-cyclodextrin inhibited delta-toxin-induced cytotoxicity and ATP depletion. Delta-toxin caused the release of carboxyfluorescein from sphingomyelin-cholesterol liposomes and formed oligomers; toxin binding to the liposomes declined with decreasing cholesterol content in the liposomes. Flow cytometric assays with annexin V and propidium iodide revealed that delta-toxin treatment induced an elevation in the population of annexin V-negative and propidium iodide-positive cells. Delta-toxin did not cause the fragmentation of DNA or caspase-3 activation. Furthermore, delta-toxin caused damage to mitochondrial membrane permeability and cytochrome c release. In the present study, we demonstrate that delta-toxin produces cytotoxic activity through necrosis.

  12. Necrosis prediction of photodynamic therapy applied to skin disorders

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; Romanov, O. G.; López-Escobar, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2009-02-01

    The great selectivity and the lack of side effects of Photodynamic Therapy make it more advantageous than radiotherapy or chemotherapy. The application of PDT to skin diseases is particularly appropriate, due to the accessibility of this tissue. Common disorders like nonmelanoma skin cancer, that includes basocelullar or squamous cell carcinomas, can be treated with PDT. Conventional procedures, like surgery or radiotherapy, are not so efficient and do not, in general, obtain the same favourable results. PDT in dermatology medical praxis uses fixed protocols depending on the photosensitizer and the optical source used. These protocols are usually provided by the photosensitizer laboratory, and every lesion is treated with the same parameters. In this work we present a photo-chemical model of PDT applied to skin disorders treated with topical photosensitizers. Optical propagation inside the tissue is calculated by means of a 3D diffusion equation, solved via a finite difference numerical method. The photosensitizer degradation or photobleaching is taken into account, as the drug looses efficiency with the irradiation time. With these data the necrosis area is estimated, so this model could be used as a predictive tool to adjust the optical power and exposition time for the particular disease under treatment.

  13. Tumor Necrosis Factor Superfamily in Innate Immunity and Inflammation

    PubMed Central

    Šedý, John; Bekiaris, Vasileios; Ware, Carl F.

    2015-01-01

    The tumor necrosis factor superfamily (TNFSF) and its corresponding receptor superfamily (TNFRSF) form communication pathways required for developmental, homeostatic, and stimulus-responsive processes in vivo. Although this receptor–ligand system operates between many different cell types and organ systems, many of these proteins play specific roles in immune system function. The TNFSF and TNFRSF proteins lymphotoxins, LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator [HVEM], a receptor expressed by T lymphocytes), lymphotoxin-β receptor (LT-βR), and HVEM are used by embryonic and adult innate lymphocytes to promote the development and homeostasis of lymphoid organs. Lymphotoxin-expressing innate-acting B cells construct microenvironments in lymphoid organs that restrict pathogen spread and initiate interferon defenses. Recent results illustrate how the communication networks formed among these cytokines and the coreceptors B and T lymphocyte attenuator (BTLA) and CD160 both inhibit and activate innate lymphoid cells (ILCs), innate γδ T cells, and natural killer (NK) cells. Understanding the role of TNFSF/TNFRSF and interacting proteins in innate cells will likely reveal avenues for future therapeutics for human disease. PMID:25524549

  14. Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis

    PubMed Central

    Seike, Soshi; Miyamoto, Kazuaki; Kobayashi, Keiko; Takehara, Masaya; Nagahama, Masahiro

    2016-01-01

    Clostridium perfringens delta-toxin is a β-pore-forming toxin and a putative pathogenic agent of C. perfringens types B and C. However, the mechanism of cytotoxicity of delta-toxin remains unclear. Here, we investigated the mechanisms of cell death induced by delta-toxin in five cell lines (A549, A431, MDCK, Vero, and Caco-2). All cell lines were susceptible to delta-toxin. The toxin caused rapid ATP depletion and swelling of the cells. Delta-toxin bound and formed oligomers predominantly in plasma membrane lipid rafts. Destruction of the lipid rafts with methyl β-cyclodextrin inhibited delta-toxin-induced cytotoxicity and ATP depletion. Delta-toxin caused the release of carboxyfluorescein from sphingomyelin-cholesterol liposomes and formed oligomers; toxin binding to the liposomes declined with decreasing cholesterol content in the liposomes. Flow cytometric assays with annexin V and propidium iodide revealed that delta-toxin treatment induced an elevation in the population of annexin V-negative and propidium iodide-positive cells. Delta-toxin did not cause the fragmentation of DNA or caspase-3 activation. Furthermore, delta-toxin caused damage to mitochondrial membrane permeability and cytochrome c release. In the present study, we demonstrate that delta-toxin produces cytotoxic activity through necrosis. PMID:26807591

  15. Tumour necrosis factor induction by malaria exoantigens depends upon phospholipid.

    PubMed Central

    Bate, C A; Taverne, J; Román, E; Moreno, C; Playfair, J H

    1992-01-01

    In patients with malaria, the clinical manifestations of the disease are associated with the presence of high concentrations of tumour necrosis factor (TNF) in the serum. Blood-stage parasites of human and rodent malarial parasites release serologically related exoantigens which induce the production of TNF in vitro and in vivo and which can kill mice made hypersensitive to TNF by pretreatment with D-galactosamine. They also elicit the production of T-independent antibody, which blocks these effects. The capacity of the exoantigens to stimulate macrophages to secrete TNF does not require the presence of protein or carbohydrate, but is associated with a lipid whose activity can be abolished by treatment with phospholipase C. Treatments of the exoantigens which destroyed their activity in vitro also abrogated their immunogenicity and their toxicity for mice. No TNF-inducing activity could be detected in preparations of parasitized erythrocytes that was not associated with phospholipid, and the TNF-inducing properties of the malarial phospholipids are quite distinct from those of bacterial lipopolysaccharide. We conclude that release of potentially toxic phospholipids by parasites may be responsible for some of the pathology of malaria. PMID:1537589

  16. Lysophosphatidic acid induces necrosis and apoptosis in hippocampal neurons.

    PubMed

    Holtsberg, F W; Steiner, M R; Keller, J N; Mark, R J; Mattson, M P; Steiner, S M

    1998-01-01

    A diverse body of evidence indicates a role for the lipid biomediator lysophosphatidic acid (LPA) in the CNS. This study identifies and characterizes the induction of neuronal death by LPA. Treatment of cultured hippocampal neurons from embryonic rat brains with 50 microM LPA resulted in neuronal necrosis, as determined morphologically and by the release of lactate dehydrogenase. A concentration of LPA as low as 10 microM led to the release of lactate dehydrogenase. In contrast, treatment of neurons with 0.1 or 1.0 microM LPA resulted in apoptosis, as determined by chromatin condensation. In addition, neuronal death induced by 1 microM LPA was characterized as apoptotic on the basis of terminal dUTP nick end-labeling (TUNEL) staining, externalization of phosphatidylserine, and protection against chromatin condensation, TUNEL staining, and phosphatidylserine externalization by treatment with N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad-spectrum inhibitor of caspases, i.e., members of the interleukin-1beta converting enzyme family. Studies with antagonists of ionotropic glutamate receptors did not indicate a significant role for these receptors in apoptosis induced by 1 microM LPA. LPA (1 microM) also induced a decrease in mitochondrial membrane potential. Moreover, pretreatment of neurons with cyclosporin A protected against the LPA-induced decrease in mitochondrial membrane potential and neuronal apoptosis. Thus, LPA, at pathophysiological levels, can induce neuronal apoptosis and could thereby participate in neurodegenerative disorders. PMID:9422348

  17. Cortical laminar necrosis related to migrainous cerebral infarction

    PubMed Central

    Arboix, Adrià; González-Peris, Sebastià; Grivé, Elisenda; Sánchez, María-José; Comes, Emili

    2013-01-01

    We present a 29-year-old woman with a long history of attacks of migraine with and without visual aura. She was a heavy smoker (20 cigarettes/d) and was currently taking oral contraceptives. During a typical migraine attack with aura, she developed dysarthria, left brachial hemiparesis and hemihypoesthesia and brief and autolimited left clonic facial movements. Four hours after onset, vascular headache and focal sensorimotor neurological deficit were the only persisting symptoms and, on seventh day, she was completely recovered. Brain magnetic resonance imaging on day 20 after onset showed a subacute ischemic lesion in the right temporo-parietal cortex compatible with cortical laminar necrosis (CLN). Extensive neurological work-up done to rule out other known causes of cerebral infarct with CLN was unrevealing. Only ten of 3.808 consecutive stroke patients included in our stroke registry over a 19-year period fulfilled the strictly defined International Headache Society criteria for migrainous stroke. The present case is the unique one in our stroke registry that presents CLN related to migrainous cerebral infarction. Migrainous infarction can result in CLN. PMID:24340278

  18. Methods to Differentiate Radiation Necrosis and Recurrent Disease in Gliomas

    NASA Astrophysics Data System (ADS)

    Ewell, Lars

    2007-03-01

    Given the difficulty in differentiating Radiation Induced Necrosis (RIN) and recurrent disease in glioma patients using conventional techniques (CT scans, MRI scans), researchers have looked for different imaging modalities. Among these different modalities are Diffusion Weighted Magnetic Resonance Imaging (DWMRI) and Magnetic Resonance Spectroscopy (MRS). In DWMRI, an Apparent Diffusion Coefficient (ADC) is calculated for a Region Of Interest (ROI), and then monitored over time (longitudinally). In the brain, different anatomical features can complicate the interpretation of ADCs. In particular, the density and spatial variation of the cerebral spinal fluid filled fissures known as sulci can influence how a change in an ADC is explained. We have used the covariance of pixel intensity in T1 weighted MRI scans to study how intra-patient and inter-patient sulci density varies, and will present these results. MRS uses the shift in the MR signal due to the local chemical environment to determine the concentration of brain metabolites like choline and creatin. The ratio of metabolites such as these has been shown to have the power to discriminate between RIN and recurrent disease in glioma patients. At our institution, we have initiated a protocol whereby we will use DWMRI and MRS to study how best to utilize these complimentary forms of imaging.

  19. Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis.

    PubMed

    Seike, Soshi; Miyamoto, Kazuaki; Kobayashi, Keiko; Takehara, Masaya; Nagahama, Masahiro

    2016-01-01

    Clostridium perfringens delta-toxin is a β-pore-forming toxin and a putative pathogenic agent of C. perfringens types B and C. However, the mechanism of cytotoxicity of delta-toxin remains unclear. Here, we investigated the mechanisms of cell death induced by delta-toxin in five cell lines (A549, A431, MDCK, Vero, and Caco-2). All cell lines were susceptible to delta-toxin. The toxin caused rapid ATP depletion and swelling of the cells. Delta-toxin bound and formed oligomers predominantly in plasma membrane lipid rafts. Destruction of the lipid rafts with methyl β-cyclodextrin inhibited delta-toxin-induced cytotoxicity and ATP depletion. Delta-toxin caused the release of carboxyfluorescein from sphingomyelin-cholesterol liposomes and formed oligomers; toxin binding to the liposomes declined with decreasing cholesterol content in the liposomes. Flow cytometric assays with annexin V and propidium iodide revealed that delta-toxin treatment induced an elevation in the population of annexin V-negative and propidium iodide-positive cells. Delta-toxin did not cause the fragmentation of DNA or caspase-3 activation. Furthermore, delta-toxin caused damage to mitochondrial membrane permeability and cytochrome c release. In the present study, we demonstrate that delta-toxin produces cytotoxic activity through necrosis. PMID:26807591

  20. Amprolium-induced cerebrocortical necrosis (CCN) in dromedary racing camels.

    PubMed

    Wernery, U; Haydn-Evans, J; Kinne, J

    1998-08-01

    Amprolium was successfully used to induce cerebrocortical necrosis (CCN) in dromedary racing camels, only when they were fed on a barley diet. Camels which were fed on hay ad libitum did not suffer form CCN, although their thiamine pyrophosphate (TPP) reached similar levels as in camels fed on barley. The reason for this phenomenon is discussed. Five camels which suffered from CCN had TPP values of 80-115% and were euthanized on humane grounds when they were in lateral recumbency. Pathohistological investigations revealed a polioencephalomalacia of the dorsal cerebral cortex with oedema and status spongiosus. Cerebral autofluorescence was observed under ultraviolet light. The major clinicopathological changes were a slight anemia and a decreased potassium value whereas glucose, muscle enzymes, leucocyte counts and differential counts were elevated. A TPP effect of 12% was found during this study in healthy dromedary racing camels and symptoms were observed when TPP values reached 80-115%. The test is now being widely used during the camel racing season.

  1. [Intestinal necrosis as clinical presentation of Takayasu arteritis].

    PubMed

    Cornejo, Rodrigo; Gatica, Héctor; Segovia, Erico; Cortés, Claudia

    2002-10-01

    A 32 years old female was admitted to hospital due to acute abdominal pain, nausea, vomiting and liquid stools. Physical examination was normal except for pain on her left inferior abdominal quadrant without peritoneal irritation signs. An abdominal CAT-scan suggested thrombosis at celiac trunk, although the echo Doppler showed no alterations except for signs of ischemia in the distal branch of the superior mesenteric artery. An exploratory laparotomy was performed disclosing a necrosis of the distal ileum and cecum, diffuse peritonitis and thrombosis of the ileocecoapendiculocolic artery. No vasculitis lesions were found in the arteries of medium size examined. A history of intermittent claudication for the past 3 years as well as acrocyanosis, asymmetry of pulses and blood pressure in the superior extremities was ascertained after the surgery. A MRI angiogram showed multiple stenoses and irregularities at the celiac trunk, hepatic, superior mesenteric and fibular arteries. No abnormalities at the aortic arch and its main branches were documented. A sepsis due to Candida sp complicated her postoperative period. After recovery, prednisone 1 mg/kg/day was started and the anticoagulation continued. The abdominal pain, intermittent claudication and superior limb acrocyanosis disappeared. This is an unusual case of type IV Takayasu's arteritis with acute abdominal signs as the first manifestation.

  2. Detection of acute hepatopancreatic necrosis disease (AHPND) in Mexico.

    PubMed

    Nunan, Linda; Lightner, Donald; Pantoja, Carlos; Gomez-Jimenez, Silvia

    2014-08-21

    Acute hepatopancreatic necrosis disease (AHPND), which has also been referred to as early mortality syndrome (EMS), initially emerged as a destructive disease of cultured shrimp species in Asia in 2009. The pathogen associated with the disease, Vibrio parahaemolyticus, subsequently spread to the Western Hemisphere and emerged in Mexico in early 2013. The spread to the Western Hemisphere is a major concern to shrimp producers in the region. To date, the only peer-reviewed published method for determining whether mortalities are due to AHPND is through histological examination. A novel PCR detection method was employed to assess samples from Mexico in order to confirm the presence of the pathogen in this country. This manuscript details the detection methods used to confirm the presence of AHPND in Mexico. Both immersion and per os challenge studies were used to expose the Penaeus vannamei to the bacteria in order to induce the disease. Histological analysis confirmed AHPND status following the challenge studies. Also provided are the details of the molecular test by PCR that was used for screening candidate V. parahaemolyticus isolates. A rapid PCR assay for detection of AHPND may help with early detection and help prevent the spread of AHPND to other countries.

  3. [Aseptic necrosis of the temporomandibular joint in systemic lupus erythematosus].

    PubMed

    Grinin, V M; Maksimovskiĭ, Iu M; Nasonova, V A

    1999-01-01

    A total of 285 patients with verified systemic lupus erythematosus (SLE) were examined. They complained of painful temporo-mandibular joint (TMJ) and/or limited mobility of the mandible. Eight patients with chronic arthritis of the TMJ and a shortened (by 3-4 mm) mandibular branch were detected. In 4 female patients aged 25-38 with SLE lasting for about 5.5 years, unilateral signs of myoarticular dysfunction of the TMJ, flattening and decrease of the articular head without erosion and destruction, subcortical round foci with uneven internal contours were found in the central or median part of the head, with the compact bone above the foci thinned and the articular surface flattened; this prompted us to regard these changes as avascular necrosis (AN) of the joint. Shortening of the mandibular branch was caused by deformation of the neck of the articular process and its declination backwards. The detected changes in the TMJ were not accompanied by involvement of other joints. All these 4 patients with SLE and TMJ AN suffered from cerebropathy with epileptic attacks (frequent in 2 patients), Raynaud's syndrome, and bright capillaries of the palms and soles; 2 patients developed clinical picture of the antiphospholipid syndrome. Computer tomography and magnetic resonance findings validating the development of TMJ AN in?

  4. Vaccinia Virus Induces Programmed Necrosis in Ovarian Cancer Cells

    PubMed Central

    Whilding, Lynsey M; Archibald, Kyra M; Kulbe, Hagen; Balkwill, Frances R; Öberg, Daniel; McNeish, Iain A

    2013-01-01

    The mechanisms by which oncolytic vaccinia virus induces tumor cell death are poorly understood. We have evaluated cell death pathways following infection of ovarian cancer cells with both wild-type and thymidine kinase-deleted (dTK) Lister strain vaccinia. We show that death does not rely upon classical apoptosis despite the appearances of some limited apoptotic features, including phosphatidylserine externalization and appearance of sub-G1 DNA populations. Vaccinia infection induces marked lipidation of LC3 proteins, but there is no general activation of the autophagic process and cell death does not rely upon autophagy induction. We show that vaccinia induces necrotic morphology on transmission electron microscopy, accompanied by marked by reductions in intracellular adenosine triphosphate, altered mitochondrial metabolism, and release of high mobility group box 1 (HMGB1) protein. This necrotic cell death appears regulated, as infection induces formation of a receptor interacting protein (RIP1)/caspase-8 complex. In addition, pharmacological inhibition of both RIP1 and substrates downstream of RIP1, including MLKL, significantly attenuate cell death. Blockade of TNF-α, however, does not alter virus efficacy, suggesting that necrosis does not result from autocrine cytokine release. Overall, these results show that, in ovarian cancer cells, vaccinia virus causes necrotic cell death that is mediated through a programmed series of events. PMID:23985697

  5. Tumor necrosis factor alpha-induced pulmonary vascular endothelial injury.

    PubMed Central

    Goldblum, S E; Hennig, B; Jay, M; Yoneda, K; McClain, C J

    1989-01-01

    Tumor necrosis factor alpha (TNF-alpha) mediates components of the acute-phase response, stimulates granulocyte metabolism, and induces endothelial cell surface changes. We studied whether human recombinant TNF-alpha (rTNF-alpha) could increase pulmonary edema formation and pulmonary vascular permeability. Rabbits preinfused with 125I-albumin were administered rTNF-alpha or saline. Animals were sacrificed, and lung wet/dry weight ratios as well as bronchoalveolar lavage fluid and plasma 125I activities were determined. rTNF-alpha increased lung wet/dry weight ratios by 151% (P less than 0.02) and bronchoalveolar lavage fluid/plasma 125I activity ratios by 376% (P less than 0.01) compared with values for saline controls. Electron microscopy of lung sections demonstrated endothelial injury, perivascular edema, and extravasation of an ultrastructural permeability tracer. To demonstrate that rTNF-alpha could directly increase pulmonary vascular endothelial permeability in vitro, we studied albumin transfer across cultured porcine pulmonary artery endothelial cell monolayers. rTNF-alpha induced time-dependent dose-response increments in transendothelial albumin flux in the absence of granulocyte effector cells. These observations suggest that rTNF-alpha can provoke acute pulmonary vascular endothelial injury in vivo as well as in vitro. Images PMID:2925247

  6. Renal papillary necrosis in haemophilia and christmas disease.

    PubMed

    Roberts, G M; Evans, K T; Bloom, A L; Al-Gailani, F

    1983-03-01

    Haematuria is common in haemophilia and Christmas disease. A variety of radiological abnormalities in the urinary tract has been described in the literature, the commonest being hydronephrosis and obstructive uropathy. The findings in 26 cases seen in this centre were reported by Beck and Evans in 1972; although urinary-tract obstruction was relatively common, it was noted that signs suggestive of renal papillary necrosis (RPN) were present in some cases. In the present study, 20 of these patients were reinvestigated up to 10 years after the original radiological studies; a total number of 46 past and present intravenous urograms were examined. There was evidence of RPN in 11 of the 20 patients, and in five of these the signs had changed over the intervening period. The relevance of these findings is discussed; none of the patients showed evidence of renal failure. It is suggested that episodes of urinary-tract obstruction could be related to papillary sloughing, in some cases, rather than clot obstruction or obstruction due to retroperitoneal bleeding.

  7. Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha

    PubMed Central

    Cai, Weibo; Kerner, Zachary J.; Hong, Hao; Sun, Jiangtao

    2013-01-01

    Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation. PMID:24115841

  8. Survival of the salmonid viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV) in ozonated, chlorinated, and Untreated waters

    USGS Publications Warehouse

    Wedemeyer, Gary A.; Nelson, Nancy C.; Smith, Cathy A.

    1978-01-01

    Ozone and chlorine inactivation curves were determined in three water types at 10 °C for the fish pathogenic viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV). In phosphate-buffered, distilled water (PBDW) an ozone dose of 0.01 mg/L for 30 or 60 s inactivated IHNV or IPNV, respectively, suspended at a tissue culture 50% infective dose (TCID50) of 104–105/mL. In hard (120 mg/L as CaCO3) and soft water (30 mg/L) lake waters, an ozone application rate of 70 mg∙h−1∙L−1 for 10 min destroyed IHNV. IPNV inactivation in hard water required 90 mg∙O3∙h−1∙L−1 for 10 min but only a 30-s contact time in soft water. The IPNV was also somewhat more resistant to chlorine. In PBDW, a residual of 0.1 mg/L with contact times of 30 and 60 s, respectively, destroyed IHNV and IPNV. In soft lake water IHNV was destroyed within 5 min at 0.5 mg/L, while in hard water a 10-min contact time was required. For IPNV disinfection in soft water, 0.2 mg/L for 10 min was sufficient but this chlorine residual had essentially no effect on IPNV in hard water. Increasing this dose to 0.7 mg/L destroyed IPNV in hard water within 2 min. In untreated waters, IPNV was stable for at least 8 wk in either distilled, soft, or hard lake waters. However, IHNV survived only about 2 wk in distilled and 7 wk in the soft or hard lake waters. We suggest the serious consideration of ozone as a fish disease control agent. Key words: ozone, chlorine disinfection, fish pathogens, viruses

  9. Necrosis, and then stress induced necrosis-like cell death, but not apoptosis, should be the preferred cell death mode for chemotherapy: clearance of a few misconceptions

    PubMed Central

    Zhang, Ju; Lou, Xiaomin; Jin, Longyu; Zhou, Rongjia; Liu, Siqi; Xu, Ningzhi; Liao, D. Joshua

    2014-01-01

    Cell death overarches carcinogenesis and is a center of cancer researches, especially therapy studies. There have been many nomenclatures on cell death, but only three cell death modes are genuine, i.e. apoptosis, necrosis and stress-induced cell death (SICD). Like apoptosis, SICD is programmed. Like necrosis, SICD is a pathological event and may trigger regeneration and scar formation. Therefore, SICD has subtypes of stress-induced apoptosis-like cell death (SIaLCD) and stress-induced necrosis-like cell death (SInLCD). Whereas apoptosis removes redundant but healthy cells, SICD removes useful but ill or damaged cells. Many studies on cell death involve cancer tissues that resemble parasites in the host patients, which is a complicated system as it involves immune clearance of the alien cancer cells by the host. Cancer resembles an evolutionarily lower-level organism having a weaker apoptosis potential and poorer DNA repair mechanisms. Hence, targeting apoptosis for cancer therapy, i.e. killing via SIaLCD, will be less efficacious and more toxic. On the other hand, necrosis of cancer cells releases cellular debris and components to stimulate immune function, thus counteracting therapy-caused immune suppression and making necrosis better than SIaLCD for chemo drug development. PMID:25594039

  10. Necrosis, and then stress induced necrosis-like cell death, but not apoptosis, should be the preferred cell death mode for chemotherapy: clearance of a few misconceptions.

    PubMed

    Zhang, Ju; Lou, Xiaomin; Jin, Longyu; Zhou, Rongjia; Liu, Siqi; Xu, Ningzhi; Liao, D Joshua

    2014-01-01

    Cell death overarches carcinogenesis and is a center of cancer researches, especially therapy studies. There have been many nomenclatures on cell death, but only three cell death modes are genuine, i.e. apoptosis, necrosis and stress-induced cell death (SICD). Like apoptosis, SICD is programmed. Like necrosis, SICD is a pathological event and may trigger regeneration and scar formation. Therefore, SICD has subtypes of stress-induced apoptosis-like cell death (SIaLCD) and stress-induced necrosis-like cell death (SInLCD). Whereas apoptosis removes redundant but healthy cells, SICD removes useful but ill or damaged cells. Many studies on cell death involve cancer tissues that resemble parasites in the host patients, which is a complicated system as it involves immune clearance of the alien cancer cells by the host. Cancer resembles an evolutionarily lower-level organism having a weaker apoptosis potential and poorer DNA repair mechanisms. Hence, targeting apoptosis for cancer therapy, i.e. killing via SIaLCD, will be less efficacious and more toxic. On the other hand, necrosis of cancer cells releases cellular debris and components to stimulate immune function, thus counteracting therapy-caused immune suppression and making necrosis better than SIaLCD for chemo drug development. PMID:25594039

  11. On the relation of necrosis and inflammation to denaturation of proteins.

    PubMed

    OPIE, E L

    1962-03-01

    Necrosis of the skin was produced by the injection of measured quantities of electrolytes and of amino compounds into the dermis, and the relative ability of these substances to produce it was determined. Inflammation characterized by edema and accumulation of leucocytes accompanied necrosis. The ability of electrolytes to produce necrosis was found to increase with the valence of their basic ion, and in this respect was in accord with their ability to denature proteins. The quantity of different electrolytes needed to produce necrosis varied in the same order as the molar concentration of these electrolytes, that is isotonic with liver or kidney cells. Necrosis caused by amino compounds occurred with similar relation to the isotonicity of liver cells. In this as in other relations the cells acted as osmometers. The foregoing relations indicate that denaturation of proteins, necrosis of living tissue, and osmotic activity of liver or kidney cells are determined by molecular weight, valence, and ion-dissociation of electrolytes, that is, by the factors that determine the colligative properties of electrolytes. Agents such as turpentine, mustard, or croton oil and some halogen substitution compounds of methyl that are insoluble in water and soluble in lipoids have produced skin necrosis and inflammation.

  12. Bevacizumab as Therapy for Radiation Necrosis in Four Children With Pontine Gliomas

    SciTech Connect

    Liu, Arthur K.; Macy, Margaret E.; Foreman, Nicholas K.

    2009-11-15

    Purpose: Diffuse pontine gliomas are a pediatric brain tumor that is fatal in nearly all patients. Given the poor prognosis for patients with this tumor, their quality of life is very important. Radiation therapy provides some palliation, but can result in radiation necrosis and associated neurologic decline. The typical treatment for this necrosis is steroid therapy. Although the steroids are effective, they have numerous side effects that can often significantly compromise quality of life. Bevacizumab, an antibody against vascular endothelial growth factor, has been suggested as a treatment for radiation necrosis. We report on our initial experience with bevacizumab therapy for radiation necrosis in pediatric pontine gliomas. Materials and Methods: Four children with pontine gliomas treated at the Children's Hospital in Denver and the University of Colorado Denver developed evidence of radiation necrosis both clinically and on imaging. Those 4 children then received bevacizumab as a treatment for the radiation necrosis. We reviewed the clinical outcome and imaging findings. Results: After bevacizumab therapy, 3 children had significant clinical improvement and were able to discontinue steroid use. One child continued to decline, and, in retrospect, had disease progression, not radiation necrosis. In all cases, bevacizumab was well tolerated. Conclusions: In children with pontine gliomas, bevacizumab may provide both therapeutic benefit and diagnostic information. More formal evaluation of bevacizumab in these children is needed.

  13. AICAR induces AMPK-independent programmed necrosis in prostate cancer cells.

    PubMed

    Guo, Feng; Liu, Shuang-Qing; Gao, Xing-Hua; Zhang, Long-Yang

    2016-05-27

    AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, which induces cytotoxic effect to several cancer cells. Its potential activity in prostate cancer cells and the underlying signaling mechanisms have not been extensively studied. Here, we showed that AICAR primarily induced programmed necrosis, but not apoptosis, in prostate cancer cells (LNCaP, PC-3 and PC-82 lines). AICAR's cytotoxicity to prostate cancer cells was largely attenuated by the necrosis inhibitor necrostatin-1. Mitochondrial protein cyclophilin-D (CYPD) is required for AICAR-induced programmed necrosis. CYPD inhibitors (cyclosporin A and sanglifehrin A) as well as CYPD shRNAs dramatically attenuated AICAR-induced prostate cancer cell necrosis and cytotoxicity. Notably, AICAR-induced cell necrosis appeared independent of AMPK, yet requiring reactive oxygen species (ROS) production. ROS scavengers (N-acetylcysteine and MnTBAP), but not AMPKα shRNAs, largely inhibited prostate cancer cell necrosis and cytotoxicity by AICAR. In summary, the results of the present study demonstrate mechanistic evidences that AMPK-independent programmed necrosis contributes to AICAR's cytotoxicity in prostate cancer cells. PMID:27103440

  14. Haplotypes of tumor necrosis factor gene and tracheal aspirate fluid levels of tumor necrosis factor-alpha in preterm infants.

    PubMed

    Kazzi, S Nadya J; Tromp, Gerard; Quasney, Michael W; Buhimschi, Irina A

    2008-08-01

    Individual variability in the production of tumor necrosis factor-alpha (TNF-alpha) has been attributed to genetic factors. We examined whether alleles of TNF gene (lymphotoxin-alpha+250, TNF-alpha-308, and TNF-alpha-238) affect tracheal aspirate fluid (TAF) levels of TNF-alpha among preterm infants at risk of bronchopulmonary dysplasia. TAF samples were collected within 48 h of birth and 7, 14, 21, and 28 d later. Haplotypes [designated using the nucleotide bases in the chromosome order (lymphotoxin-alpha+250, TNF-alpha-308, TNF-alpha-238)] of TNF were correlated with levels of TNF-alpha. Diplotypes of TNF (genotypes of haplotypes) classified as high, intermediate, or low based on their relation to TAF TNF-alpha levels were also correlated with TNF-alpha levels. The most frequent (and reference haplotype) was AGG. The GGG haplotype was associated with the lowest TAF TNF-alpha levels on day 7 among African American infants (p < 0.008). Sequential changes in levels of TNF-alpha correlated with infants' diplotype status [high (HH), intermediate (HL), low (LL)]. Fetal chorioamnionitis but not bronchopulmonary dysplasia was associated with infants' diplotypes (p < 0.005). Haplotypes of the TNF gene influence TAF levels of TNF-alpha. Diplotypes of TNF are associated with fetal chorioamnionitis.

  15. Use of tumor necrosis factor (TNF) inhibitors in patients with HIV/AIDS.

    PubMed

    Gallitano, Stephanie M; McDermott, Laura; Brar, Kanwaljit; Lowenstein, Eve

    2016-05-01

    Patients with HIV and AIDS are living longer because of advancements in antiretroviral therapy. These patients are often susceptible to debilitating inflammatory disorders that are refractory to standard treatment. We discuss the relationship of tumor necrosis factor-alpha and HIV and then review 27 published cases of patients with HIV being treated with tumor necrosis factor-alpha inhibitors. This review is limited because no randomized controlled trials have been performed with this patient population. Regardless, we propose that reliable seropositive patients, who are adherent to medication regimens and frequent monitoring and have failed other treatment modalities, should be considered for treatment with tumor necrosis factor-alpha inhibitors.

  16. Bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in five painted storks.

    PubMed

    Weber, Martha A; Terrell, Scott P; Neiffer, Donald L; Miller, Michele A; Mangold, Barbara J

    2002-08-01

    Five painted storks were treated with fenbendazole for 5 days for internal parasitism. Four birds died following treatment. Profound heteropenia was a consistent finding in all samples evaluated; additionally, the 1 surviving bird had progressive anemia. Consistent necropsy findings in the 4 birds that died were small intestinal crypt cell necrosis and severe bone marrow depletion and necrosis. Fenbendazole has been associated with bone marrow hypoplasia and enteric damage in mammals and other species of birds. The dosages of fenbendazole used in birds are often substantially higher than those recommended for mammals, which may contribute to bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in birds.

  17. Skin and soft tissue necrosis from calcium chloride in a deicer.

    PubMed

    Kim, Min P; Raho, Vittorio J; Mak, John; Kaynar, A Murat

    2007-01-01

    Calcium chloride salt is the principle ingredient of many commercially available deicers. Calcium chloride melts snow and ice by its osmotic action. We present a case of skin and soft tissue necrosis associated with the use of a calcium chloride-containing deicer. Although calcium chloride is known to produce soft tissue necrosis if it extravasates during intravenous administration, necrosis and skin sloughing has rarely been described after topical exposure to this salt. Calcium chloride likely produces tissue injury from the heat liberated by mixing calcium chloride with water (exothermic reaction) and from direct calcium deposits in the skin (calcinosis cutis) and soft tissue.

  18. Regulation of bitter taste responses by tumor necrosis factor

    PubMed Central

    Feng, Pu; Jyotaki, Masafumi; Kim, Agnes; Chai, Jinghua; Simon, Nirvine; Zhou, Minliang; Bachmanov, Alexander A.; Huang, Liquan; Wang, Hong

    2015-01-01

    Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases. PMID:25911043

  19. Fibrinolytic response to tumor necrosis factor in healthy subjects.

    PubMed

    van der Poll, T; Levi, M; Büller, H R; van Deventer, S J; de Boer, J P; Hack, C E; ten Cate, J W

    1991-09-01

    Tumor necrosis factor (TNF) may be involved in the disturbance of the procoagulant-fibrinolytic balance in septicemia, leading to microvascular thrombosis. To assess the dynamics of the fibrinolytic response to TNF in humans, we performed a crossover saline-controlled study in six healthy men, investigating the effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2) on the stimulation and inhibition of plasminogen activation as well as on plasmin activity and inhibition. TNF induced a brief fourfold increase in the overall plasma plasminogen activator (PA) activity peaking after 1 h (p less than 0.0001), which was associated with rises in the antigenic levels of urokinase-type plasminogen activator (p less than 0.0001) and tissue-type plasminogen activator (p less than 0.0001). Plasminogen activator inhibitor type I antigen remained unchanged in the first hour, but showed a rapid eightfold increase thereafter (p less than 0.0001), which coincided with the decrease in PA activity. Generation of plasmin activity in the first hour was signified by an 11-fold rise in D-dimer levels (p less than 0.0001); inhibition of plasmin was reflected by a 36-fold rise in plasmin-alpha 2 antiplasmin complexes (p less than 0.0001), as well as by a transient 16% decrease in alpha 2-antiplasmin activity (p less than 0.01). In conclusion, TNF induced an early activation of the fibrinolytic system becoming maximal in 1 h, with a rapid inhibition thereafter. Earlier observations in the same subjects showed sustained coagulation activation for 6-12 h. The observed disbalance between the procoagulant and fibrinolytic mechanisms after TNF injection confirms the in vivo relevance of the effects of TNF on vascular endothelium in vitro and may explain the tendency towards microvascular thrombosis in septicemia.

  20. Regulation of bitter taste responses by tumor necrosis factor.

    PubMed

    Feng, Pu; Jyotaki, Masafumi; Kim, Agnes; Chai, Jinghua; Simon, Nirvine; Zhou, Minliang; Bachmanov, Alexander A; Huang, Liquan; Wang, Hong

    2015-10-01

    Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases. PMID:25911043

  1. Regulation of bitter taste responses by tumor necrosis factor.

    PubMed

    Feng, Pu; Jyotaki, Masafumi; Kim, Agnes; Chai, Jinghua; Simon, Nirvine; Zhou, Minliang; Bachmanov, Alexander A; Huang, Liquan; Wang, Hong

    2015-10-01

    Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases.

  2. Efficacy of certain disinfectants against infectious pancreatic necrosis virus

    USGS Publications Warehouse

    Elliott, Diane G.; Amend, Donald F.

    1978-01-01

    The virucidal properties of iodophor, chlorine (sodium hypochlorite), formalin, thimerosal (organic mercurial compound), malachite green, and acriflavine were tested on infectious pancreatic necrosis virus (IPNV). Iodine and chlorine showed good activity, but efficacy depended on the concentration of virus, the presence of organic matter (calf serum), and water pH. Water hardness (0-300 mg 1−1 as CaCO3) did not affect virucidal activity. In a 5 min exposure, 4 mg 1−1available iodine inactivated 103.9 TCID50 m1−1 IPNV but 16 mg 1−1 iodine were needed for inactivation of 106.3TCID50m1−1. The addition of 0-5% calf serum significantly reduced the iodine concentration and the virucidal activity. In comparison, 4 mg 1−1 chlorine were needed to inactivate 1046 TCID50 m1−1 IPNV in 5 min. However, the addition of 0-07 % serum greatly reduced the chlorine concentration and extended the virucidal contact time to 30 min or more. IPNV at 106.3 TCID60 m1−1 was not inactivated by exposures for 60 min to 0-2% formalin, 10 min to 0-2% thimerosal, 60 min to 5 mg 1−1 malachite green, or 20 min to 500 mg 1−1 acriflavine. However, acriflavine at 0-5 mg 1−1 in cell culture media prevented the development of cytopathology caused by IPNV and may be useful in the treatment of the disease.

  3. Exogenous tumour necrosis factor α induces suppression of autoimmune arthritis

    PubMed Central

    2008-01-01

    Introduction Our previous studies showed that arthritic Lewis (LEW) rats produced the highest levels of tumour necrosis factor (TNF)α in the recovery phase of adjuvant arthritis (AA), suggesting a correlation between high TNFα levels and reduced severity of arthritis. To further explore this correlation, we compared the TNFα secretion profile of the AA-resistant Wistar Kyoto (WKY) rats with that of LEW rats, determined the effect of exogenous TNFα on the course of AA in LEW rats, and examined various mechanisms involved in TNFα-induced disease modulation. Methods A cohort each of LEW and WKY rats was immunised subcutaneously with heat-killed Mycobacterium tuberculosis H37Ra (Mtb). At different time points thereafter, subgroups of rats were killed and their draining lymph node cells were tested for cytokine production. Another group of LEW rats was injected with TNFα intraperitoneally daily for a total of 10 injections, 3 before and 6 after Mtb challenge, and then observed for signs of AA. In parallel, TNFα-treated rats were examined for changes in other cytokines, in CD4+CD25+ T cell frequency, and in indoleamine 2,3-dioxygenase (IDO) mRNA expression levels. Results LEW rats displayed a TNFα secretion profile that was opposite to that of the WKY rats. Furthermore, TNFα treatment significantly downmodulated the severity of AA in LEW rats, and decreased the interferon (IFN)-γ secretion in response to the pathogenic determinant of the disease-related antigen. No significant alterations were observed in other parameters tested. Conclusion The role of endogenous TNFα in the induction and propagation of arthritis is well established. However, exogenous TNFα can downmodulate the course of AA, displaying an immunoregulatory functional attribute of this cytokine. PMID:18380898

  4. Tumor necrosis factor-inducing activities of Cryptococcus neoformans components.

    PubMed Central

    Delfino, D; Cianci, L; Migliardo, M; Mancuso, G; Cusumano, V; Corradini, C; Teti, G

    1996-01-01

    Cryptococcus neoformans-induced tumor necrosis factor alpha (TNF-alpha) production may lead to increased human immunodeficiency virus replication in patients with AIDS. In order to identify cryptococcal components that are predominantly responsible for stimulating TNF production, various concentrations of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), mannoproteins (MP), and alpha(1-3) [corrected] glucan were added to whole-blood cultures. All of the cryptococcal components tested, as well as whole heat-killed cryptococci, were capable of inducing TNF-alpha release in a dose-dependent manner. MP were significantly more potent than any of the other cryptococcal components tested or heat-killed cryptococci in stimulating TNF-alpha production (P < 0.05). GXM, in contrast, was significantly less potent in this activity than either GalXM or MP (P < 0.05). As little as 0.5 microg of MP per ml was sufficient to produce moderate but significant elevations of TNF-alpha release. Maximal MP-induced TNF-alpha levels were similar to those induced by Salmonella enteritidis lipopolysaccharide, our positive control. Further experiments using isolated leukocytes suggested that monocytes were the cell population mainly responsible for TNF-alpha production, although the participation of other cell types could not be excluded. The presence of complement-sufficient plasma was a necessary requirement for TNF-alpha induction by GXM, GalXM, and low doses of MP. High MP concentrations (100 microg/ml) were also capable of stimulating TNF-alpha production in the absence of plasma. These data indicate that soluble products released by C. neoformans are capable of inducing TNF-alpha secretion in human leukocytes. This may be clinically relevant, since high concentrations of such products are frequently found in the body fluids of AIDS patients infected with C. neoformans. PMID:8945566

  5. Pathogenesis of acute hepatopancreatic necrosis disease (AHPND) in shrimp.

    PubMed

    Lai, Hung-Chiao; Ng, Tze Hann; Ando, Masahiro; Lee, Chung-Te; Chen, I-Tung; Chuang, Jie-Cheng; Mavichak, Rapeepat; Chang, Sheng-Hsiung; Yeh, Mi-De; Chiang, Yi-An; Takeyama, Haruko; Hamaguchi, Hiro-o; Lo, Chu-Fang; Aoki, Takashi; Wang, Han-Ching

    2015-12-01

    Acute hepatopancreatic necrosis disease (AHPND), also called early mortality syndrome (EMS), is a recently emergent shrimp bacterial disease that has resulted in substantial economic losses since 2009. AHPND is known to be caused by strains of Vibrio parahaemolyticus that contain a unique virulence plasmid, but the pathology of the disease is still unclear. In this study, we show that AHPND-causing strains of V. parahaemolyticus secrete the plasmid-encoded binary toxin PirAB(vp) into the culture medium. We further determined that, after shrimp were challenged with AHPND-causing bacteria, the bacteria initially colonized the stomach, where they started to produce PirAB(vp) toxin. At the same early time point (6 hpi), PirB(vp) toxin, but not PirA(vp) toxin, was detected in the hepatopancreas, and the characteristic histopathological signs of AHPND, including sloughing of the epithelial cells of the hepatopancreatic tubules, were also seen. Although some previous studies have found that both components of the binary PirAB(vp) toxin are necessary to induce a toxic effect, our present results are consistent with other studies which have suggested that PirB(vp) alone may be sufficient to cause cellular damage. At later time points, the bacteria and PirA(vp) and PirB(vp) toxins were all detected in the hepatopancreas. We also show that Raman spectroscopy "Whole organism fingerprints" were unable to distinguish between AHPND-causing and non-AHPND causing strains. Lastly, by using minimum inhibitory concentrations, we found that both virulent and non-virulent V. parahaemolyticus strains were resistant to several antibiotics, suggesting that the use of antibiotics in shrimp culture should be more strictly regulated. PMID:26549178

  6. Upregulation of tumor necrosis factor alpha and interleukin-1 beta in Q fever endocarditis.

    PubMed Central

    Capo, C; Zugun, F; Stein, A; Tardei, G; Lepidi, H; Raoult, D; Mege, J L

    1996-01-01

    The occurrence of Q fever endocarditis likely involves some alterations in the responses of monocytes, the in vivo targets of Coxiella burnetii. To test this hypothesis, the production of the inflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 was assessed in monocytes from patients with Q fever endocarditis. Spontaneous transcription and secretion of tumor necrosis factor and interleukin-1 were significantly higher in patient monocytes than in healthy controls. The interleukin-6 transcripts were also upregulated in patient cells. Moreover, in patients with recent endocarditis exhibiting high titers of immunoglobulin G directed to C. burnetii in phase I, monocytes released significantly higher levels of tumor necrosis factor and interleukin-1 than in patients with stabilized endocarditis. Immunoglobulin G titers and the overproduction of tumor necrosis factor and interleukin-1 were significantly correlated. Hence, the overproduction of inflammatory cytokines might be a marker of disease activity. PMID:8613372

  7. Herpesviral Hematopoietic Necrosis in Goldfish in Switzerland: Early Lesions in Clinically Normal Goldfish (Carassius auratus).

    PubMed

    Giovannini, S; Bergmann, S M; Keeling, C; Lany, C; Schütze, H; Schmidt-Posthaus, H

    2016-07-01

    Cyprinid herpesvirus 2 is a pathogen of goldfish, inducing a disease referred to as herpesviral hematopoietic necrosis. The disease is described so far in Japan, North America, Taiwan, Australia, the United Kingdom, and recently also Italy. Here the authors describe histologic lesions in clinically affected fish in comparison with clinically normal but virus DNA-positive goldfish in Switzerland. While necrosis or enhanced single-cell necrosis in the hematopoietic tissue in the pronephros or mesonephros was evident in dead and sick animals, in clinically normal goldfish, only single-cell necrosis was observed. Virus DNA was demonstrated in dead as well as clinically affected and subclinically infected goldfish by polymerase chain reaction and in situ hybridization. This study identifies the presence of goldfish herpesvirus in Switzerland and highlights the fact that the virus might be more widespread than assumed, as clinically normal goldfish can also carry cyprinid herpesvirus 2, showing histologically similar lesions but of lesser extent and severity. PMID:26553521

  8. Acute esophageal necrosis occurring in a patient undergoing percutaneous coronary intervention.

    PubMed

    Kwon, Hyung-Jin; Park, Sang-Ho; Ahn, Ji-Hoon; Lee, Tae-Hoon; Lee, Chang-Kyun

    2014-05-01

    Acute esophageal necrosis is uncommon in the literature. Its etiology is unknown, although cardiovascular disease, hemodynamic compromise, gastric outlet obstruction, alcohol ingestion, hypoxemia, hypercoagulable state, infection, and trauma have all been suggested as possible causes. A 67-year-old female underwent a coronary angiography (CAG) for evaluation of chest pain. CAG findings showed coronary three-vessel disease. We planned percutaneous coronary intervention (PCI). Coronary arterial dissection during the PCI led to sudden hypotension. Six hours after the index procedure, the patient experienced a large amount of hematemesis. Emergency gastrofibroscopy was performed and showed mucosal necrosis with a huge adherent blood clot in the esophagus. After conservative treatment for 3 months, the esophageal lesion was completely improved. She was diagnosed with acute esophageal necrosis. We report herein a case of acute esophageal necrosis occurring in a patient undergoing percutaneous coronary intervention. PMID:24851074

  9. Necrosis in benign salivary gland neoplasms. Not necessarily a sign of malignant transformation.

    PubMed

    Allen, C M; Damm, D; Neville, B; Rodu, B; Page, D; Weathers, D R

    1994-10-01

    Necrosis that occurs in a salivary gland neoplasm is usually considered to be an ominous sign, suggesting malignant transformation, particularly in lesions that have had no prior manipulation such as fine-needle aspiration. We describe five pleomorphic adenomas and two canalicular adenomas of salivary gland origin that exhibited necrosis, yet were otherwise benign. All lesions displayed a distinctive histopathologic pattern characterized by a narrow rim of viable tumor tissue at the periphery of the neoplasm combined with a diffuse central region that demonstrated apparent ischemic necrosis. No invasion of adjacent normal tissue was identified, and no recurrence or metastasis has been seen with these lesions. Caution should be exercised in the evaluation of salivary gland neoplasms with central necrosis to avoid misdiagnosis of all such lesions as malignant.

  10. [Brain radiation necrosis after stereotactic radiotherapy of the resection cavity for intracranial metastases: analysis of the literature from four cases].

    PubMed

    Doré, M; Lefebvre, L; Delpon, G; Thillays, F

    2015-04-01

    Stereotactic hypofractionated radiotherapy after resection of brain metastasis is an alternative to whole brain radiotherapy. A high dose per fraction is associated with a risk of radiation necrosis. We present four cases of confirmed histological radiation necrosis. Differentiating recurrent tumour from radiation necrosis in this scenario is challenging. An enhancing area in magnetic resonance imaging (MRI) with a "cut bell pepper" appearance may suggest radiation necrosis. Advanced imaging modalities such as perfusion MR imaging and positron emission tomography can be useful. Dosimetric predictors of the occurrence of radiation necrosis after stereotactic hypofractionated radiotherapy are poorly understood and require prospective studies on larger cohorts.

  11. [Brain radiation necrosis after stereotactic radiotherapy of the resection cavity for intracranial metastases: analysis of the literature from four cases].

    PubMed

    Doré, M; Lefebvre, L; Delpon, G; Thillays, F

    2015-04-01

    Stereotactic hypofractionated radiotherapy after resection of brain metastasis is an alternative to whole brain radiotherapy. A high dose per fraction is associated with a risk of radiation necrosis. We present four cases of confirmed histological radiation necrosis. Differentiating recurrent tumour from radiation necrosis in this scenario is challenging. An enhancing area in magnetic resonance imaging (MRI) with a "cut bell pepper" appearance may suggest radiation necrosis. Advanced imaging modalities such as perfusion MR imaging and positron emission tomography can be useful. Dosimetric predictors of the occurrence of radiation necrosis after stereotactic hypofractionated radiotherapy are poorly understood and require prospective studies on larger cohorts. PMID:25573799

  12. A case series of skin necrosis following use of non invasive ventilation pressure masks.

    PubMed

    Ahmad, Z; Venus, M; Kisku, W; Rayatt, S S

    2013-02-01

    Two cases of nasal skin necrosis secondary to pressure from the use of continuous positive airway pressure (CPAP) face masks are presented. Both developed skin necrosis as a result of wearing these masks over the nasal bridge. These cases highlight the need for clinical vigilance in application of CPAP masks, the need for monitoring the skin of the nose during CPAP use and the possible need for modifications in design to help prevent this serious complication. PMID:22432901

  13. Analysis of risk factors for femoral head necrosis after internal fixation in femoral neck fractures.

    PubMed

    Wang, Tao; Sun, Jun-Ying; Zha, Guo-Chun; Jiang, Tao; You, Zhen-Jun; Yuan, De-Jing

    2014-12-01

    Femoral head necrosis is a rare but devastating complication following femoral neck fracture. The reported incidence of avascular necrosis after femoral neck fracture fixation varies widely, and there is no consensus regarding its risk factors. The aim of this study was to analyze the risk factors for femoral head necrosis after internal fixation in femoral neck fracture. This retrospective study included 166 patients with femoral neck fractures treated with surgical reduction and internal fixation at the authors' institution from January 2004 to December 2008. Eight patients died for reasons unrelated to the surgery, and 12 patients were lost to follow-up. The remaining 146 patients (146 fractures) were followed until union or until conversion to total hip arthroplasty. The patients included 61 males and 85 females with an average age of 47.5 years (range, 18-68 years). The authors analyzed the following factors: age, sex, Garden classification, reduction quality, surgical methods, injury-to-surgery interval, preoperative traction, weight-bearing time, and implant removal. All patients were followed for a mean of 52 months (range, 6-90 months). The incidence of femoral head necrosis was 14.4% (21/146). Garden classification (P=.012), reduction quality (P=.008), implant removal (P=.020), and preoperative traction (P=.003) were significantly associated with femoral head necrosis. Patient age (P=.990), sex (P=.287), injury-to-surgery interval (P=.360), weight-bearing time (P=.868), and surgical methods (P=.987) were not significantly associated with femoral head necrosis. In multivariate logistic regression analysis, implant removal was not a significant risk factor for femoral head necrosis development (P=.498). Garden classification, reduction quality, and preoperative traction had a significant effect on femoral head necrosis development. PMID:25437087

  14. [Intracardiac mass: Why not a liquefaction necrosis of a mitral annulus calcification?].

    PubMed

    Leddet, P; Couppié, P; De Poli, F; Uhry, S; Hanssen, M

    2015-11-01

    We report the case of an asymptomatic 70-year-old woman with a liquefaction necrosis of mitral annulus calcification. This mass was discovered incidentally during an echocardiographic examination. Additional treatment was not performed because liquefaction necrosis of mitral calcification usually has a benign prognosic. A scheduled clinical review with an echocardiographic examination and cardiac MRI was planified. The patient is actually healthy without any complication.

  15. Tumor necrosis factor-alpha and ceramides in insulin resistance.

    PubMed

    Brindley, D N; Wang, C N; Mei, J; Xu, J; Hanna, A N

    1999-01-01

    The present studies tested the hypothesis that some effects of tumor necrosis factor-alpha (TNF-alpha) are mediated by activation of sphingomyelinases and the production of ceramides. Differentiated 3T3-L1 adipocytes were incubated with short-chain ceramide analogs, (C2- and C6-ceramides: N-acetyl- and N-hexanoyl-sphingosines, respectively), and this treatment increased 2-deoxyglucose uptake in the absence of insulin progressively from 2-24 h. This effect was inhibited by blocking the activations of mitogen-activated protein kinase, phosphatidylinositol 3-kinase (PI 3-kinase), and ribosomal S6 kinase which mediated an increase in GLUT1 concentrations. Long-term increases in PI 3-kinase activity associated with insulin receptor substrate-1 (IRS-1) increased the proportion of GLUT1 and GLUT4 in plasma membranes. These events explain the increases in noninsulin-dependent glucose uptake and incorporation of this glucose into the fatty acid and glycerol moieties of triacylglycerol. The mechanisms by which TNF-alpha and ceramides increase PI 3-kinase activity were investigated further by using rat2 fibroblasts. Incubation for 20 min with TNF-alpha, bacterial sphingomyelinase, or C2-ceramides increased PI 3-kinase activity by about fivefold, and this effect depended upon a stimulation of tyrosine kinase activity and an increase in Ras-GTP. This demonstrates the existence of a novel signaling pathway for TNF-alpha that could contribute to the effects of this cytokine in stimulating basal glucose uptake. By contrast, treating the 3T3-L1 adipocytes for 2-24 h with C2-ceramide diminished insulin-stimulated glucose uptake by decreasing the insulin-induced translocation of GLUT1 and GLUT4 to plasma membranes. This inhibition was observed when there was no increase in basal glucose uptake, and it occurred downstream of PI 3-kinase. Our work provides further mechanisms whereby TNF-alpha and ceramides produce insulin resistance and decrease the effectiveness of insulin in

  16. Characterization of tumor necrosis factor-deficient mice.

    PubMed

    Marino, M W; Dunn, A; Grail, D; Inglese, M; Noguchi, Y; Richards, E; Jungbluth, A; Wada, H; Moore, M; Williamson, B; Basu, S; Old, L J

    1997-07-22

    Although tumor necrosis factor (TNF) initially came to prominence because of its anti-tumor activity, most attention is now focused on its proinflammatory actions. TNF appears to play a critical role in both early and late events involved in inflammation, from localizing the noxious agent and amplifying the cellular and mediator responses at the local site and systemically, to editing (e.g., apoptosis) injured cells or effete immune cells and repairing inflammatory damage. We have generated mice deficient in TNF (TNF-/- mice) and have begun to examine the multiple functions attributed to TNF. TNF-/- mice develop normally and have no gross structural or morphological abnormalities. As predicted, they are highly susceptible to challenge with an infectious agent (Candida albicans), are resistant to the lethality of minute doses of lipopolysaccharide (LPS) following D-galactosamine treatment, have a deficiency in granuloma development, and do not form germinal centers after immunization. Phagocytic activity of macrophages appears relatively normal, as do T cell functions, as measured by proliferation, cytokine release, and cytotoxicity. B cell response to thymus-independent antigens is normal, but the Ig response to thymus-dependent antigen is reduced. Surprisingly, cytokine production induced by LPS appears essentially intact, with the exception of reduced colony-stimulating factor activity. Other unexpected findings coming from our initial analysis are as follows. (i) TNF has low toxicity in TNF-/- mice. (ii) TNF-/- mice show an anomalous late response to heat-killed Corynebacterium parvum. In contrast to the prompt response (granuloma formation, hepatosplenomegaly) and subsequent resolution phase in C. parvum-injected TNF+/+ mice, similarly treated TNF-/- mice show little or no initial response, but then develop a vigorous, disorganized inflammatory response leading to death. These results suggest that TNF has an essential homeostatic role in limiting the extent and

  17. Response-driven imaging biomarkers for predicting radiation necrosis of the brain

    NASA Astrophysics Data System (ADS)

    Nazem Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-05-01

    Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy (RT). Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Twenty-nine patients with glioblastoma received six weeks of intensity modulated RT and concurrent temozolomide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p = 0.05 and p = 0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid the prediction of delayed radiation necrosis, which could provide guidance in dose-escalation trials.

  18. Fast Neutron Induced Autophagy Leads To Necrosis In Glioblastoma Multiforme Cells

    NASA Astrophysics Data System (ADS)

    Yasui, Linda; Gladden, Samantha; Andorf, Christine; Kroc, Thomas

    2011-06-01

    Fast neutrons are highly effective at killing glioblastoma multiforme (GBM), U87 and U251 cells. The mode of cell death was investigated using transmission electron microscopy (TEM) to identify the fraction of irradiated U87 or U251 cells having morphological features of autophagy and/or necrosis. U87 or U251 cells were irradiated with 2 Gy fast neturons or 10 Gy γ rays. A majority of U87 and U251 cells exhibit features of cell death with autophagy after irradiation with either 10 Gy γ rays or 2 Gy fast neutrons. Very few γ irradiated cells had features of necrosis (U87 or U251 cell samples processed for TEM 1 day after 10 Gy γ irradiation). In contrast, a significant increase was observed in necrotic U87 and U251 cells irradiated with fast neutrons. These results show a greater percentage of cells exhibit morphological evidence of necrosis induced by a lower dose of fast neutron irradiation compared to γ irradiation. Also, the evidence of necrosis in fast neutron irradiated U87 and U251 cells occurs in a background of autophagy. Since autophagy is observed before necrosis, autophagy may play a role in signaling programmed necrosis in fast neutron irradiated U87 and U251 cells.

  19. Fast Neutron Induced Autophagy Leads To Necrosis In Glioblastoma Multiforme Cells

    SciTech Connect

    Yasui, Linda; Gladden, Samantha; Andorf, Christine; Kroc, Thomas

    2011-06-01

    Fast neutrons are highly effective at killing glioblastoma multiforme (GBM), U87 and U251 cells. The mode of cell death was investigated using transmission electron microscopy (TEM) to identify the fraction of irradiated U87 or U251 cells having morphological features of autophagy and/or necrosis. U87 or U251 cells were irradiated with 2 Gy fast neturons or 10 Gy {gamma} rays. A majority of U87 and U251 cells exhibit features of cell death with autophagy after irradiation with either 10 Gy {gamma} rays or 2 Gy fast neutrons. Very few {gamma} irradiated cells had features of necrosis (U87 or U251 cell samples processed for TEM 1 day after 10 Gy {gamma} irradiation). In contrast, a significant increase was observed in necrotic U87 and U251 cells irradiated with fast neutrons. These results show a greater percentage of cells exhibit morphological evidence of necrosis induced by a lower dose of fast neutron irradiation compared to {gamma} irradiation. Also, the evidence of necrosis in fast neutron irradiated U87 and U251 cells occurs in a background of autophagy. Since autophagy is observed before necrosis, autophagy may play a role in signaling programmed necrosis in fast neutron irradiated U87 and U251 cells.

  20. Dependency of tissue necrosis on gelatin sponge particle size after canine hepatic artery embolization

    SciTech Connect

    Sonomura, Tetsuo; Yamada, Ryusaku; Kishi, Kazushi; Nishida, Norifumi; Yang, Ren J.; Sato, Morio

    1997-01-15

    Purpose. To determine the optimal size of gelatin sponge particles (GSPs) to produce maximum tumor necrosis with minimum side effects after canine hepatic artery embolization (HAE). Methods. GSPs were separated into four size ranges: A, up to 200 {mu}m (mean 152) as Gelfoam powder; B, 200-500 {mu}m (mean 336) as Gelfoam powder; C, 500-1000 {mu}m (mean 649) as Spongel; and D, 1000-2000 {mu}m (mean 1382) as Spongel. Three mongrel dogs were assigned randomly to HAE with each particle size. On day 7 after HAE, the livers were removed and subjected to pathological examination. Results. The mean volume of liver necrosis was 11% after embolization, with particle size A, 36.3% with B, 0% with C, and 1% with D. Coagulation necrosis was found in all livers with particles of sizes A and B, and in 1 of 6 with sizes C and D. Bile duct injury was found in five of six dogs with sizes A and B and in none with sizes C and D. Gallbladder necrosis was found in one dog with size B and pancreas necrosis in one with size A. Conclusion. GSPs of 500 {mu}m are considered optimally effective for tissue necrosis according to this model.

  1. Rapid Detection of Necrosis in Breast Cancer with Desorption Electrospray Ionization Mass Spectrometry

    PubMed Central

    Tata, Alessandra; Woolman, Michael; Ventura, Manuela; Bernards, Nicholas; Ganguly, Milan; Gribble, Adam; Shrestha, Bindesh; Bluemke, Emma; Ginsberg, Howard J.; Vitkin, Alex; Zheng, Jinzi; Zarrine-Afsar, Arash

    2016-01-01

    Identification of necrosis in tumors is of prognostic value in treatment planning, as necrosis is associated with aggressive forms of cancer and unfavourable outcomes. To facilitate rapid detection of necrosis with Mass Spectrometry (MS), we report the lipid MS profile of necrotic breast cancer with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) imaging validated with statistical analysis and correlating pathology. This MS profile is characterized by (1) the presence of the ion of m/z 572.48 [Cer(d34:1) + Cl]− which is a ceramide absent from the viable cancer subregions; (2) the absence of the ion of m/z 391.25 which is present in small abundance only in viable cancer subregions; and (3) a slight increase in the relative intensity of known breast cancer biomarker ions of m/z 281.25 [FA(18:1)-H]− and 303.23 [FA(20:4)-H]−. Necrosis is accompanied by alterations in the tissue optical depolarization rate, allowing tissue polarimetry to guide DESI-MS analysis for rapid MS profiling or targeted MS imaging. This workflow, in combination with the MS profile of necrosis, may permit rapid characterization of necrotic tumors from tissue slices. Further, necrosis-specific biomarker ions are detected in seconds with single MS scans of necrotic tumor tissue smears, which further accelerates the identification workflow by avoiding tissue sectioning and slide preparation. PMID:27734938

  2. Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones.

    PubMed

    Zhang, Dongjian; Jiang, Cuihua; Yang, Shengwei; Gao, Meng; Huang, Dejian; Wang, Xiaoning; Shao, Haibo; Feng, Yuanbo; Sun, Ziping; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2016-01-01

    Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone compounds with the same substituents but different skeletal structures, namely Hypericin (Hyp), protohypericin (ProHyp), emodin dianthrone mesomer (ED-1) and emodin dianthrone raceme (ED-2) were synthesized and radioiodinated. Then radioiodinated dianthrones were evaluated in vitro for their necrosis avidity in A549 lung cancer cells untreated and treated with H2O2. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. In vitro cell assay revealed that destruction of rigid skeleton structure dramatically reduced their necrosis targeting ability. Animal studies demonstrated that destruction of rigid skeleton structure dramatically reduced the necrotic tissue uptake and speed up the clearance from the most normal tissues for the studied compounds. Among these (131)I-dianthrones, (131)I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using (131)I-Hyp as an imaging probe. The results suggest that the skeleton structure of Hyp is the lead structure for further structure optimization of this class of NAAs.

  3. Response-driven Imaging Biomarkers for Predicting Radiation Necrosis of the Brain

    PubMed Central

    Nazem-Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-01-01

    Purpose Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy. Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Methods and Materials Twenty-nine patients with glioblastoma received six weeks of intensity modulated radiation therapy (RT) and concurrent temozolamide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Results Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p=0.05 and p=0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Conclusions Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid in predicting delayed radiation necrosis, which could provide guidance in dose-escalation trials. PMID:24778364

  4. Induction of inflammatory cell infiltration and necrosis in normal mouse skin by the combined treatment of tumor necrosis factor and lithium chloride.

    PubMed Central

    Beyaert, R.; De Potter, C.; Vanhaesebroeck, B.; Van Roy, F.; Fiers, W.

    1991-01-01

    Previously we reported that lithium chloride (LiCl) potentiates tumor necrosis factor (TNF)-mediated cytotoxicity in vitro and in vivo. Here, using a murine normal skin model, it is shown that a subcutaneous injection of TNF plus LiCl induces acute dermal and subcutaneous inflammation and necrosis. Histology showed a marked initial dermal and subcutaneous neutrophil infiltrate by approximately 2 hours, followed by a predominantly mononuclear infiltrate by 24 hours, which remained present for several days. Tumor necrosis factor or LiCl alone induced negligible inflammation, disappearing after 6 hours; furthermore there was never necrosis or ulceration of the overlying skin in case of single-agent application. In vitro studies showed that the combination of TNF and LiCl, but not either agent alone, was directly cytotoxic to fibroblastic cells of murine skin. No inflammatory infiltration was visible in tumors treated intratumorally or perilesionally with TNF plus LiCl, although the latter treatment resulted in a perilesional leukocyte infiltration. Furthermore the combination of TNF and LiCl had no effect on macrophage cytotoxicity to L929 tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 PMID:1848044

  5. Dose–Volume Relationships Associated With Temporal Lobe Radiation Necrosis After Skull Base Proton Beam Therapy

    SciTech Connect

    McDonald, Mark W.; Linton, Okechukwu R.; Calley, Cynthia S.J.

    2015-02-01

    Purpose: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. Methods and Materials: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluated potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose–volume parameters associated with radiation necrosis. Results: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose–volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm{sup 3}, or aV70 > 1.7 cm{sup 3}. Conclusions: Dose–volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm{sup 3} or aV70 > 1.7 cm{sup 3}. Treatment planning goals should include constraints on the volume of temporal lobes receiving

  6. Activation of coagulation after administration of tumor necrosis factor to normal subjects.

    PubMed

    van der Poll, T; Büller, H R; ten Cate, H; Wortel, C H; Bauer, K A; van Deventer, S J; Hack, C E; Sauerwein, H P; Rosenberg, R D; ten Cate, J W

    1990-06-01

    Tumor necrosis factor has been implicated in the activation of blood coagulation in septicemia, a condition commonly associated with intravascular coagulation and disturbances of hemostasis. To evaluate the early dynamics and the route of the in vivo coagulative response to tumor necrosis factor, we performed a controlled study in six healthy men, monitoring the activation of the common and intrinsic pathways of coagulation with highly sensitive and specific radioimmunoassays. Recombinant human tumor necrosis factor, administered as an intravenous bolus injection (50 micrograms per square meter of body-surface area), induced an early and short-lived rise in circulating levels of the activation peptide of factor X, reaching maximal values after 30 to 45 minutes (mean +/- SEM increase after 45 minutes, 34.2 +/- 18.2 percent; tumor necrosis factor vs. saline, P = 0.015). This was followed by a gradual and prolonged increase in the plasma concentration of the prothrombin fragment F1+2, peaking after four to five hours (mean increase after five hours, 348.0 +/- 144.8 percent; tumor necrosis factor vs. saline, P less than 0.0001). These findings signify the formation of factor Xa (activated factor X) and the activation of prothrombin. Activation of the intrinsic pathway could not be detected by a series of measurements of the plasma levels of factor XII, prekallikrein, factor XIIa-C1 inhibitor complexes, kallikrein-C1 inhibitor complexes, and the activation peptide of factor IX. The delay between the maximal activation of factor X and that of prothrombin amounted to several hours, indicating that neutralization of factor Xa activity was slow. We conclude that a single injection of tumor necrosis factor elicits a rapid and sustained activation of the common pathway of coagulation, probably induced through the extrinsic route. Our results suggest that tumor necrosis factor could play an important part in the early activation of the hemostatic mechanism in septicemia.

  7. Predisposing Factors of Liver Necrosis after Transcatheter Arterial Chemoembolization in Liver Metastases from Neuroendocrine Tumor

    SciTech Connect

    Joskin, Julien Baere, Thierry de; Auperin, Anne; Tselikas, Lambros Guiu, Boris Farouil, Geoffroy; Boige, Valérie Malka, David; Leboulleux, Sophie; Ducreux, Michel; Baudin, Eric; Deschamps, Frédéric

    2015-04-15

    PurposeTo investigate predictive factors for liver necrosis after transcatheter arterial chemoembolization (TACE) of neuroendocrine liver metastases.MethodsA total of 164 patients receiving 374 TACE were reviewed retrospectively to analyze predictive factors of liver necrosis. We analyzed patient age and sex; metastasis number and location; percentage of liver involvement; baseline liver function test; and pretreatment imaging abnormalities such as bile duct dilatation (BDD), portal vein narrowing (PVN), and portal vein thrombosis (PVT). We analyzed TACE technique such as Lipiodol or drug-eluting beads (DEB) as the drug’s vector; dose of chemotherapy; diameter of DEB; and number, frequency, and selectivity of TACE.ResultsLiver necrosis developed after 23 (6.1 %) of 374 TACE. In multivariate analysis, DEB > 300 μm in size induced more liver necrosis compared to Lipiodol (odds ratio [OR] 35.20; p < 0.0001) or with DEB < 300 μm in size (OR 19.95; p < 0.010). Pretreatment BDD (OR 119.64; p < 0.0001) and PVT (OR 9.83; p = 0.030) were predictive of liver necrosis. BDD or PVT responsible for liver necrosis were present before TACE in 59 % (13 of 22) and were induced by a previous TACE in 41 % (9 of 22) of cases.ConclusionDEB > 300 μm in size, BDD, and PVT are responsible for increased rate of liver necrosis after TACE. Careful analysis of BDD or PVT on pretreatment images as well as images taken between two courses can help avoid TACE complications.

  8. Apoptosis and necrosis during the circadian cycle in the centipede midgut.

    PubMed

    Rost-Roszkowska, M M; Chajec, Ł; Vilimova, J; Tajovský, K

    2016-07-01

    Three types of cells have been distinguished in the midgut epithelium of two centipedes, Lithobius forficatus and Scolopendra cingulata: digestive, secretory, and regenerative cells. According to the results of our previous studies, we decided to analyze the relationship between apoptosis and necrosis in their midgut epithelium and circadian rhythms. Ultrastructural analysis showed that these processes proceed in a continuous manner that is independent of the circadian rhythm in L. forficatus, while in S. cingulata necrosis is activated at midnight. Additionally, the description of apoptosis and necrosis showed no differences between males and females of both species analyzed. At the beginning of apoptosis, the cell cytoplasm becomes electron-dense, apparently in response to shrinkage of the cell. Organelles such as the mitochondria, cisterns of endoplasmic reticulum transform and degenerate. Nuclei gradually assume lobular shapes before the apoptotic cell is discharged into the midgut lumen. During necrosis, however, the cytoplasm of the cell becomes electron-lucent, and the number of organelles decreases. While the digestive cells of about 10 % of L. forficatus contain rickettsia-like pathogens, the corresponding cells in S. cingulata are free of rickettsia. As a result, we can state that apoptosis in L. forficatus is presumably responsible for protecting the organism against infections, while in S. cingulata apoptosis is not associated with the elimination of pathogens. Necrosis is attributed to mechanical damage, and the activation of this process coincides with proliferation of the midgut regenerative cells at midnight in S. cingulata.

  9. Beethoven's renal disease based on his autopsy: a case of papillary necrosis.

    PubMed

    Schwarz, A

    1993-06-01

    The autopsy report of Ludwig van Beethoven written by Dr Johann Wagner in 1827 reveals that he had renal calculi that had not been diagnosed during his lifetime, together with perirenal fibrosis. The most comprehensive interpretation of this autopsy finding is that the regular calcareous deposits in every one of his renal calices represented calcified necrotic papillae. Severe urinary obstruction or diabetes as possible causes of papillary necrosis were not present. Analgesic abuse because of headaches, back pain, and attacks of rheumatism or gout may be presumed on the basis of Beethoven's uncontrolled way of taking medication. Salicin, a commonly used analgesic substance of that time (dried and powdered willow bark), is able to cause papillary necrosis. Perirenal fibrosis may be due to chronic infection or drug intake. Beethoven's other well-known diseases are deafness caused by otosclerosis of the inner ear, relapsing attacks of diarrhea as the symptoms of irritable bowel syndrome, and liver cirrhosis following viral hepatitis and chronic alcohol consumption. Liver cirrhosis also may cause papillary necrosis. In Beethoven's case, renal papillary necrosis was most probably the consequence of analgesic abuse together with decompensated liver cirrhosis. The autopsy report of Beethoven is the first case of papillary necrosis recorded in the literature.

  10. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis.

    PubMed

    Figarella-Branger, Dominique; Mokhtari, Karima; Colin, Carole; Uro-Coste, Emmanuelle; Jouvet, Anne; Dehais, Caroline; Carpentier, Catherine; Villa, Chiara; Maurage, Claude-Alain; Eimer, Sandrine; Polivka, Marc; Vignaud, Jean-Michel; Laquerriere, Annie; Sevestre, Henri; Lechapt-Zalcman, Emmanuelle; Quintin-Roué, Isabelle; Aubriot-Lorton, Marie-Hélène; Diebold, Marie-Danièle; Viennet, Gabriel; Adam, Clovis; Loussouarn, Delphine; Michalak, Sophie; Rigau, Valérie; Heitzmann, Anne; Vandenbos, Fanny; Forest, Fabien; Chiforeanu, Danchristian; Tortel, Marie-Claire; Labrousse, François; Chenard, Marie-Pierre; Nguyen, Anh Tuan; Varlet, Pascale; Kemeny, Jean Louis; Levillain, Pierre-Marie; Cazals-Hatem, Dominique; Richard, Pomone; Delattre, Jean-Yves

    2015-07-01

    Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.

  11. Beethoven's renal disease based on his autopsy: a case of papillary necrosis.

    PubMed

    Schwarz, A

    1993-06-01

    The autopsy report of Ludwig van Beethoven written by Dr Johann Wagner in 1827 reveals that he had renal calculi that had not been diagnosed during his lifetime, together with perirenal fibrosis. The most comprehensive interpretation of this autopsy finding is that the regular calcareous deposits in every one of his renal calices represented calcified necrotic papillae. Severe urinary obstruction or diabetes as possible causes of papillary necrosis were not present. Analgesic abuse because of headaches, back pain, and attacks of rheumatism or gout may be presumed on the basis of Beethoven's uncontrolled way of taking medication. Salicin, a commonly used analgesic substance of that time (dried and powdered willow bark), is able to cause papillary necrosis. Perirenal fibrosis may be due to chronic infection or drug intake. Beethoven's other well-known diseases are deafness caused by otosclerosis of the inner ear, relapsing attacks of diarrhea as the symptoms of irritable bowel syndrome, and liver cirrhosis following viral hepatitis and chronic alcohol consumption. Liver cirrhosis also may cause papillary necrosis. In Beethoven's case, renal papillary necrosis was most probably the consequence of analgesic abuse together with decompensated liver cirrhosis. The autopsy report of Beethoven is the first case of papillary necrosis recorded in the literature. PMID:8503419

  12. A Novel Murine Model for Localized Radiation Necrosis and its Characterization Using Advanced Magnetic Resonance Imaging

    SciTech Connect

    Jost, Sarah C.; Hope, Andrew; Kiehl, Erich; Perry, Arie; Travers, Sarah; Garbow, Joel R.

    2009-10-01

    Purpose: To develop a murine model of radiation necrosis using fractionated, subtotal cranial irradiation; and to investigate the imaging signature of radiation-induced tissue damage using advanced magnetic resonance imaging techniques. Methods and Materials: Twenty-four mice each received 60 Gy of hemispheric (left) irradiation in 10 equal fractions. Magnetic resonance images at 4.7 T were subsequently collected using T1-, T2-, and diffusion sequences at selected time points after irradiation. After imaging, animals were killed and their brains fixed for correlative histologic analysis. Results: Contrast-enhanced T1- and T2-weighted magnetic resonance images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 {mu}m{sup 2}/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 {mu}m{sup 2}/ms) (p < 0.0001). Histology reflected changes typically seen in radiation necrosis. Conclusions: This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that diffusion-weighted imaging may be helpful in answering this diagnostic question in clinical settings.

  13. Apoptosis and necrosis during the circadian cycle in the centipede midgut.

    PubMed

    Rost-Roszkowska, M M; Chajec, Ł; Vilimova, J; Tajovský, K

    2016-07-01

    Three types of cells have been distinguished in the midgut epithelium of two centipedes, Lithobius forficatus and Scolopendra cingulata: digestive, secretory, and regenerative cells. According to the results of our previous studies, we decided to analyze the relationship between apoptosis and necrosis in their midgut epithelium and circadian rhythms. Ultrastructural analysis showed that these processes proceed in a continuous manner that is independent of the circadian rhythm in L. forficatus, while in S. cingulata necrosis is activated at midnight. Additionally, the description of apoptosis and necrosis showed no differences between males and females of both species analyzed. At the beginning of apoptosis, the cell cytoplasm becomes electron-dense, apparently in response to shrinkage of the cell. Organelles such as the mitochondria, cisterns of endoplasmic reticulum transform and degenerate. Nuclei gradually assume lobular shapes before the apoptotic cell is discharged into the midgut lumen. During necrosis, however, the cytoplasm of the cell becomes electron-lucent, and the number of organelles decreases. While the digestive cells of about 10 % of L. forficatus contain rickettsia-like pathogens, the corresponding cells in S. cingulata are free of rickettsia. As a result, we can state that apoptosis in L. forficatus is presumably responsible for protecting the organism against infections, while in S. cingulata apoptosis is not associated with the elimination of pathogens. Necrosis is attributed to mechanical damage, and the activation of this process coincides with proliferation of the midgut regenerative cells at midnight in S. cingulata. PMID:26277351

  14. [Avascular necrosis of the femoral head in a patient with severe aplastic anaemia].

    PubMed

    Plichta, Piotr; Pawelec, Katarzyna

    2011-01-01

    Avascular necrosis (AVN) is a pathological condition associated with numerous processes. Most frequent causes of ischaemia of the femoral head include trauma, corticosteroid therapy, radiation therapy, alcoholism, Gaucher's disease, systemic lupus erythematosus, rheumatoid arthritis. Corticosteroid therapy is considered the most frequent risk factor for developing avascular necrosis. In this paper we report a case of a 19-year old female patient who developed avascular necrosis of the right femoral head following treatment of severe aplastic anaemia. Clinical symptoms included groin pain and fever, painful abduction and internal rotation, tenderness over the right hip joint. The plain X-ray was not specific. However magnetic resonance imaging of the hip revealed changes characteristic for avascular necrosis. Conservative treatment was administrated. Two years after the onset of first clinical symptoms the patient is able to walk without pain, although the range of motion of the right hip joint is partially diminished. We evaluated the possible risk factors of AVN, diagnostic methods and prognosis. The onset of avascular necrosis should be considered as one of the relevant complications in patients with severe aplastic anaemia following immunosuppressive treatment. PMID:21786520

  15. Segmental myofiber necrosis in myotonic dystrophy - An immunoperoxidase study of immunoglobulins in skeletal muscle.

    PubMed Central

    Silver, M. M.; Banerjee, D.; Hudson, A. J.

    1983-01-01

    Because serum immunoglobulin G levels are low in patients with myotonic dystrophy, it was hypothesized that it might be catabolized within abnormal muscle fibers. Accordingly, immunohistochemical stains for immunoglobulins were performed on muscle sections derived at biopsy or autopsy from patients with myotonic dystrophy, other forms of muscular dystrophy, nondystrophic muscle disease, or normal muscle. Positive staining for immunoglobulins was found only in necrotic segments of myofibers (in 7 of 19 dystrophic and 6 of 27 nondystrophic subjects), and it is believed that the staining was due to nonspecific diffusion. However, staining reactions distinguished between incipient necrosis and artifactual contraction bands and allowed us to study segmental myofiber necrosis, comparing its frequency in the various muscle diseases. Segmental myofiber necrosis was present in 4 of 16 cases of myotonic dystrophy. The relevance of this finding to the clinical and morphologic features of myotonic dystrophy is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:6351629

  16. Delayed-type Necrosis after Soft-tissue Augmentation with Hyaluronic Acid

    PubMed Central

    Klotz De Almeida Balassiano, Laila; Roos Mariano Da Rocha, Camila; Barbosa De Sousa Padilha, Carolina; Martinezt Torrado, Carolina; Teixeira Da Silva, Roberta; Carlos Regazzi Avelleira, João

    2015-01-01

    The growing use of dermal fillers, specifically the use of hyaluronic acid, can be explained by their effectiveness and versatility as well as their favorable safety profiles. Nevertheless, early and late complications with varying levels of severity may occur. The incidence of complications is low and the majority of adverse events are mild (edema, erythema, and local ecchymosis) and of limited duration. However, more severe events, such as ischemia and necrosis, may occur. The symptoms of ischemia can occur immediately after the injection or several hours after the procedure. Here, the authors report three cases of necrosis after hyaluronic acid injection with the first symptoms presenting only several hours after the procedure. The patients were treated immediately after the diagnosis. The aim of this review is to communicate the possibility of the delayed-type presentation of necrosis, present the signs and symptoms that lead to early diagnosis, and review the treatment possibilities of this severe complication. PMID:26705447

  17. Recombinant tumour necrosis factor inhibits malaria parasites in vivo but not in vitro.

    PubMed Central

    Taverne, J; Tavernier, J; Fiers, W; Playfair, J H

    1987-01-01

    As tumour necrosis serum kills malarial parasites in vitro and inhibits the multiplication of some species of Plasmodium in mice, we examined the effect of recombinant mouse tumour necrosis factor (rTNF) on P. yoelii both in vitro and in vivo. Parasites incubated overnight with rTNF showed no loss of viability, but repeated injection of rTNF into infected mice reduced parasitaemia and significantly prolonged survival of mice infected with a lethal variant of the parasite. We conclude that TNF acts on blood-stage malaria in vivo via a host cell and that another molecule in tumour necrosis serum is involved in killing the parasite in vitro. PMID:3621669

  18. Mobile encapsulated bodies comprising fat necrosis and fibrous tissue in the abdominal cavity of cows.

    PubMed

    Herzog, K; Burgdorf, W; Hewicker-Trautwein, M

    2010-11-01

    The microscopical features of 18 samples of fat necrosis and/or fibrous tissue removed from the abdominal cavity during laparotomy from 15 cows were studied. The nodular, ivory-coloured mobile structures were free-floating in the abdominal cavity, were not attached to any abdominal tissues or organs, and were completely surrounded by a fibrous capsule. Abdominal fat necrosis (bovine lipomatosis) was not observed in any animal. The structures comprised either necrotic fat, fibrous tissue or varying proportions of both. Focal calcification and mild inflammatory cell infiltration and accumulations of haemosiderin were also present. Microscopically, the lesions resembled encapsulated fat necrosis occurring in human subcutaneous tissue. The mechanisms of development of these mobile encapsulated bodies in cows is unknown and it is not clear how, in the absence of a blood supply, there can be inflammatory cell infiltration, calcification and proliferation of fibroblasts.

  19. Differential modulation of apoptosis and necrosis by antioxidants in immunosuppressed human lymphocytes.

    PubMed

    Rojas, Mauricio; Rugeles, María Teresa; Gil, Diana Patricia; Patiño, Pablo

    2002-04-15

    In the present study, we explored whether mitogenic stimulation of dexamethasone (DXM)- and cyclosporine A (CsA)-immunosuppressed peripheral blood lymphocytes (PBML) induced apoptosis or necrosis and their relation with the production of reactive oxygen intermediates. Our results indicate that both phenomena can occur in these cells and that antioxidants such as N-acetyl cysteine (NAC) and ascorbic acid (AA) can modulate them. However, DXM-induced apoptosis was only partially inhibited by NAC and AA, suggesting that DXM-treated PBMC had an additional apoptotic pathway independent of ROIs. Furthermore, we observed that the inhibition of apoptosis by antioxidants correlated with an increased cell proliferation, suggesting that the immunomodulation of both DXM and CsA may be related to induction of apoptosis. The ability to differentially modulate apoptosis and necrosis by antioxidants opens new possibilities in the management of immunosuppressive therapy, since the inhibition of necrosis may avoid inflammation and the tissue damage associated with immunosuppressors.

  20. Freestyle Perforator-Based Fasciocutaneous Flap Reconstruction in Nicolau Syndrome-Related Tissue Necrosis.

    PubMed

    Kocman, Emre A; Yaşar, Fatih N; Kose, Aydan A; Cil, Yakup; Karabagli, Yakup; Çetin, Cengiz

    2015-12-01

    The actual pathology of the Nicolau syndrome (NS) is still unknown. It is thought to involve direct vascular damage and vasospasm. Many NS cases were reported in the literature but a treatment protocol is still not established. However, after demarcation of the necrotic tissue, surgical intervention is mandatory. Five NS cases with extensive tissue necrosis on the upper lateral gluteal region were analyzed retrospectively. Operative technique was described in details for freestyle perforator-based fasciocutaneous flaps from the gluteal region to reconstruct defects of NS-related tissue necrosis. Freestyle perforator-based fasciocutaneous flaps were used for defect closure in all patients. All flaps survived totally. No complications occurred during the follow-up period. Although rare, NS is a serious complication of inadvertent intramuscular injections. Prevention is the best treatment. However, in case of large-tissue necrosis, freestyle perforator-based fasciocutaneous flaps harvested from the gluteal region is a satisfactory option for reconstruction. PMID:27011533

  1. Muscle necrosis in the extremities: evaluation with Tc-99m pyrophosphate scanning--a retrospective review

    SciTech Connect

    Timmons, J.H.; Hartshorne, M.F.; Peters, V.J.; Cawthon, M.A.; Bauman, J.M.

    1988-04-01

    A retrospective review was done of 34 extremities studied between 1981 and 1985 with technetium-99m pyrophosphate scanning; 22 were subsequently amputated. Results of detailed pathologic examination or immediate postoperative examination of the resected extremity were available in 16 cases. In these cases, scanning had allowed correct prediction of the level of amputation and of the specific areas of muscle infarction in 13 cases. In the one case in which amputation was performed for infection rather than muscle necrosis, the lack of necrosis was correctly predicted with the scan. The limited results of this study indicate that the Tc-99m pyrophosphate scan allows the location of necrotic muscle to be predicted accurately and may therefore be a useful adjunct in determining the best level for ultimate amputation. Special caution is required in those cases in which muscle necrosis is due to acute causes (e.g., traumatic thrombosis) rather than chronic vascular disease.

  2. [Maternal adrenal necrosis in the third trimester of pregnancy: a rare complication of antiphospholipid syndrome].

    PubMed

    Legendre, G; Vauthier-Brouzes, D; Cornet, A; Al Hawari, M; Renard-Penna, R; Piette, J-C; Dommergues, M

    2008-04-01

    Adrenal necrosis, a rare life threatening complication of antiphospholipid syndrome, is difficult to diagnose during pregnancy. We report the case of a 33-year-old woman with bilateral adrenal necrosis which started during the third trimester of her second pregnancy. Antiphospholipid syndrome had been diagnosed few years ago, after a thrombotic event. The pregnancy was uneventful until 36 weeks plus five days, when the patient was admitted for bilateral back ache, initially considered as uterine contractions. Labour was induced because pain persisted and was associated with major thrombocytopenia. A healthy infant was delivered vaginally on the second day, adrenal failure was diagnosed based on intense asthenia, persistent severe lumbar pain, low blood sodium and cortisol. Bilateral adrenal oedema was documented by CT scan and MRI. Symptoms resolved following administration of hydrocortisone and fludrocortisone. This case illustrates the difficulty to diagnose adrenal necrosis in the third trimester of pregnancy.

  3. Chronic respiratory failure due to toxic epidermal necrosis in a 10 year old girl.

    PubMed

    Thimmesch, M; Gilbert, A; Tuerlinckx, D; Bodart, E

    2015-02-01

    Toxic epidermal necrosis is a severe mucocutaneous disease with a high mortality rate. A third of the patients surviving the acute phase will develop pulmonary complications. The most frequent complication is bronchiolitis obliterans. Despite well-conducted treatment, in most cases, lung injury often leads to chronic respiratory failure. We describe here the case of a young patient that presented a toxic epidermal necrosis at the age of 3 years. Poor therapeutic compliance result in chronic respiratory failure and after 7 years of follow-up, pulmonary transplant remains the only long-term alternative. Close monitoring of respiratory symptoms in the course of toxic epidermal necrosis, intense treatment as soon as they appear and a long-term follow-up are essential to postpone chronic respiratory failure. PMID:25324191

  4. Spontaneous, isolated caecal necrosis: report of a case, review of the literature, and updated classification.

    PubMed

    Hunter, J P; Saratzis, A; Zayyan, K

    2013-01-01

    Isolated necrosis of the caecum is a rare cause of abdominal pain. In the absence of occlusive vascular disease it has a number of well documented associations, the commonest of which is patients' receiving haemodialysis for endstage renal failure. It has also been associated with shock states, cardiac failure, ischaemic heart disease, diabetes and drugs such as cocaine, thiopentone and cytotoxic agents. However, there are few reported cases in the literature without the aforementioned associations and the majority of cases, regardless of aetiology, were treated with either hemicolectomy or wedge resection and ileocolic anastamosis. This report describes a case of isolated caecal necrosis, mimicking acute appendicitis, successfully treated by local excision of the necrotic segment. It also provides a systematic review of the literature and proposes an updated classification of associations in isolated caecal necrosis.

  5. Adrenocortical hemorrhagic necrosis: the role of catecholamines and retrograde medullary-cell embolism

    SciTech Connect

    Szabo, S.; McComb, D.J.; Kovacs, K.; Huettner, I.

    1981-10-01

    We investigated the pathogenesis of adrenal necrosis using animal models of the disease (induced by administration of acrylonitrile, cysteamine, or pyrazole) and human cases. Results of electron-microscopic and histochemical time-response studies with rat models revealed an early, retrograde embolization of medullary cells and cell fragments in the cortical capillaries that showed prominent endothelial injury. The experimental adrenal lesions were prevented by surgical removal of the medulla one month before administration of adrenocorticolytic chemicals, or by the administration of the alpha-adrenergic antagonist phenoxybenzamine hydrochloride. Histochemical staining for medullary (argyrophil) granules in human cases of adrenal necrosis demonstrated tissue fragments that stained positively for silver in vascular cortical spaces in nine of ten autopsy specimens and in all four surgical cases we reviewed. Thus, catecholamines released from the adrenal medulla and from the retrograde medullary emboli in the cortex may have a role in the pathogenesis of adrenocortical necrosis.

  6. Renal papillary necrosis following regular consumption of non-steroidal anti-inflammatory drugs.

    PubMed

    Munn, E; Lynn, K L; Bailey, R R

    1982-04-14

    Since phenacetin was removed from the Drug Tariff in New Zealand in 1974 there has been a decrease in the number of patients with analgesic nephropathy entering dialysis-transplant programmes. Since then there has been an increase in the consumption of non-steroidal anti-inflammatory agents. Experimental work in animals has shown that these drugs can cause renal papillary necrosis. We report two men with sever osteoarthritis who regularly ingested anti-inflammatory agents and developed papillary necrosis with renal insufficiency and hypertension. One patient consumed 0.5 kg of indomethacin over 10 years and the other 3.5 kg of ibuprofen, 200 g of naproxen and an uncertain amount of ketoprofen over 13 years. The increased chronic usage of non-steroidal anti-inflammatory drugs could bring about an upsurge in the incidence of papillary necrosis.

  7. Aseptic necrosis in compressed air tunnel workers using current OSHA decompression schedules.

    PubMed

    Kindwall, E P; Nellen, J R; Spiegelhoff, D R

    1982-10-01

    Aseptic necrosis (dysbaric osteonecrosis) was discovered in two compressed air tunnel workers who had used the present Occupational Health and Safety Administration (OSHA) decompression tables for compressed air tunneling at pressures greater than 36 pounds per square inch gauge (psig). A roentgenographic study was made of 21 men who had worked at pressures up to 43 psig using the OSHA schedules. Bone scanning was also included. Seven of the men (33%) were found to have aseptic necrosis involving the shoulders, hips or distal femoral shafts and proximal tibia. It became evident that the present OSHA schedules caused not only an unacceptable incidence of decompression sickness but also aseptic necrosis at pressures over 36 psig. New interim tables that are more conservative and that use either air or oxygen as a breathing gas during decompression are undergoing laboratory and worksite evaluation.

  8. Acute hemorrhagic pancreatitis (massive necrosis) with fat necrosis induced in mice by DL-ethionine fed with a choline-deficient diet.

    PubMed Central

    Lombardi, B.; Estes, L. W.; Longnecker, D. S.

    1975-01-01

    Female, albino mice were fed a choline-deficient diet containing 0.5% DL-ethionine. All animals died within 5 days due to the development of an acute hemorrhagic pancreatis with fat necrosis throughout the peritoneal cavity. The apancreatitis was characterized by a massive necrosis of the exocrine parenchyma with intense hemorrhage and inflammatory reaction of the stroma. The sequence of histologic and ultrastructural alterations occurring in the acinar cells of the pancreas were studied in mice fed the diet for 1, 2, and 3 days. Major findings consited of accumulation of zymogen granules, vacuolation due to foci of cytoplasmic degradation, and alterations in the morphology of the zymogen granules. The pancreatitis appears to be due to intraparenchymal activation of zymogens, resulting from a synergistic action of choline deficiency with the basic toxicity of ethionine toward the acinar cells of the pancreas. The experimental model simulates closely the acute hemorrhagic pancreatitis with fat necrosis occurring in humans and may prove useful for exploring the pathogenesis of this condition. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 Fig 8 Fig 9 Fig 10 Fig 11 Fig 12 Fig 13 PMID:1094837

  9. Dietary ergot alkaloids as a possible cause of tail necrosis in rabbits.

    PubMed

    Korn, A K; Gross, M; Usleber, E; Thom, N; Köhler, K; Erhardt, G

    2014-11-01

    This study describes the association between tail necrosis in rabbits and mycotoxins in rabbit feed. Clinical cases of tail necrosis were observed in 14 out of 103 rabbits kept in an outdoor group housing, fed with hay and a commercial pelleted feed. The observed clinical symptoms, alopecia, erosions, crusts and necrosis were restricted to the tail area and exclusively occurred in young rabbits aged 113 ± 20 days. Dermatological examination suggested that ischemia had caused necrosis. Analysis of blood samples showed an elevated level of creatine kinase. No weight loss occurred in affected rabbits. Trauma caused by injuries or technopathic lesions was also excluded. Histopathologically, the lesions were characterized by acute muscle fibre degeneration and chronic active dermatitis with granulation tissue formation. Necropsy of one rabbit revealed hepatocellular degeneration and necrosis as remarkable findings. Feed analysis for ergot alkaloids by enzyme immunoassays yielded a mean and maximum ergot alkaloid content of 410 ± 250 μg/kg and 1,700 μg/kg, respectively. Faeces of affected rabbits contained ergot alkaloids at levels up to 200 μg/kg. The mean and maximum dietary intake of total ergot alkaloids were 17 and 71 μg/kg bodyweight, respectively. Fusarium toxins (trichothecenes, zearalenone, fumonisins) were also found in the feed, but at levels which did not explain the observed effects. The results indicate that ergot alkaloids may have been the cause of tail necrosis, which is supported by literature data showing that rabbits are especially sensitive towards these toxins. PMID:25234267

  10. A GSK-3β Inhibitor Protects Against Radiation Necrosis in Mouse Brain

    SciTech Connect

    Jiang, Xiaoyu; Perez-Torres, Carlos J.; Thotala, Dinesh; Engelbach, John A.; Yuan, Liya; Cates, Jeremy; Gao, Feng; Drzymala, Robert E.; Rich, Keith M.; Schmidt, Robert E.; Ackerman, Joseph J.H.; Hallahan, Dennis E.; Garbow, Joel R.

    2014-07-15

    Purpose: To quantify the effectiveness of SB415286, a specific inhibitor of GSK-3β, as a neuroprotectant against radiation-induced central nervous system (brain) necrosis in a mouse model. Methods and Materials: Cohorts of mice were treated with SB415286 or dimethyl sulfoxide (DMSO) prior to irradiation with a single 45-Gy fraction targeted to the left hemisphere (brain) using a gamma knife machine. The onset and progression of radiation necrosis (RN) were monitored longitudinally by noninvasive in vivo small-animal magnetic resonance imaging (MRI) beginning 13 weeks postirradiation. MRI-derived necrotic volumes for SB415286- and DMSO-treated mice were compared. MRI results were supported by correlative histology. Results: Mice treated with SB415286 showed significant protection from radiation-induced necrosis, as determined by in vivo MRI with histologic validation. MRI-derived necrotic volumes were significantly smaller at all postirradiation time points in SB415286-treated animals. Although the irradiated hemispheres of the DMSO-treated mice demonstrated many of the classic histologic features of RN, including fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, and tissue loss, the irradiated hemispheres of the SB415286-treated mice consistently showed only minimal tissue damage. These studies confirmed that treatment with a GSK-3β inhibitor dramatically reduced delayed time-to-onset necrosis in irradiated brain. Conclusions: The unilateral cerebral hemispheric stereotactic radiation surgery mouse model in concert with longitudinal MRI monitoring provided a powerful platform for studying the onset and progression of RN and for developing and testing new neuroprotectants. Effectiveness of SB415286 as a neuroprotectant against necrosis motivates potential clinical trials of it or other GSK-3β inhibitors.

  11. Necrosis of the Ventral Penile Skin Flap: A Complication of Hypospadias Surgery in Children

    PubMed Central

    Bakal, Ünal; Abeş, Musa; Sarac, Mehmet

    2015-01-01

    Objectives. To review cases of hypospadias that were repaired with TIPU method and consequently resulted in the necrosis of ventral penile skin flaps. Methods. Eighty-three patients with hypospadias underwent TIPU procedure by two surgeons. Neourethra in all patients was covered with dartos flap prepared from the preputium or penile shaft. In cases where ventral skin could not be covered primarily, closure was ensured by using preputial Ombredanne or Byars' flaps to repair ventral defects. Results. The median age of patients was 4 years. Twenty-five (30.12%) patients that underwent hypospadias repair had urethral opening at the coronal level, 33 (39.75%) at the distal penis, 10 (12.04%) at the midpenis, and 15 (18.07%) at the proximal penis. The ventral skin defect could not be primarily covered in 10 patients with penile shaft hypospadias. Consequently, Byars' method was used in 8 of these patients to cover the defect and the Ombredanne method was used in the remaining 2. Ventral skin flap necrosis developed in 5 patients (4 Byars and 1 Ombredanne). It was medically treated in 4 patients. Urethral fistula developed in the other patient whose necrosis was deeper. The mean hospital stay was 7 days for patients without necrosis, and 14 for those with necrosis. Conclusion. We are of the opinion that dartos flaps used in the TIPU method in order to cover neourethra and decrease the incidence of fistula development lead to necrosis in the Ombredanne or Byars' flaps by causing low blood supply to the preputium and thus extend hospital stay. PMID:25922604

  12. Thioacetamide-induced Hepatocellular Necrosis Is Attenuated in Diet-induced Obese Mice.

    PubMed

    Shirai, Makoto; Arakawa, Shingo; Miida, Hiroaki; Matsuyama, Takuya; Kinoshita, Junzo; Makino, Toshihiko; Kai, Kiyonori; Teranishi, Munehiro

    2013-06-01

    To assess modification of thioacetamide-induced hepatotoxicity in mice fed a high-fat diet, male C57BL/6J mice were fed a normal rodent diet or a high-fat diet for 8 weeks and then treated once intraperitoneally with thioacetamide at 50 mg/kg body weight. At 24 and 48 hours after administration, massive centrilobular hepatocellular necrosis was observed in mice fed the normal rodent diet, while the necrosis was less severe in mice fed the high-fat diet. In contrast, severe swelling of hepatocytes was observed in mice fed the high-fat diet. In addition, mice fed the high-fat diet displayed more than a 4-fold higher number of BrdU-positive hepatocytes compared with mice fed the normal rodent diet at 48 hours after thioacetamide treatment. To clarify the mechanisms by which the hepatic necrosis was attenuated, we investigated exposure to thioacetamide and one of its metabolites, the expression of CYP2E1, which converts thioacetamide to reactive metabolites, and the content of glutathione S-transferases in the liver. However, the reduced hepatocellular necrosis noted in mice fed the high-fat diet could not be explained by the differences in exposure to thioacetamide or thioacetamide sulfoxide or by differences in the expression of drug-metabolizing enzymes. On the other hand, at 8 hours after thioacetamide administration, hepatic total glutathione in mice fed the high-fat diet was significantly lower than that in mice fed the normal diet. Hence, decreased hepatic glutathione amount is a candidate for the mechanism of the attenuated necrosis. In conclusion, this study revealed that thioacetamide-induced hepatic necrosis was attenuated in mice fed the high-fat diet. PMID:23914059

  13. Lipolysis of visceral adipocyte triglyceride by pancreatic lipases converts mild acute pancreatitis to severe pancreatitis independent of necrosis and inflammation.

    PubMed

    Patel, Krutika; Trivedi, Ram N; Durgampudi, Chandra; Noel, Pawan; Cline, Rachel A; DeLany, James P; Navina, Sarah; Singh, Vijay P

    2015-03-01

    Visceral fat necrosis has been associated with severe acute pancreatitis (SAP) for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly understood. Based on recent work suggesting that pancreatic fat lipolysis plays an important role in SAP, we evaluated the role of pancreatic lipases in SAP-associated visceral fat necrosis, the inflammatory response, local injury, and outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced in lean and obese mice, alone or with the lipase inhibitor orlistat and parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic necrosis, and multisystem organ failure, and inflammatory response were assessed. Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1 cells. We noted obesity to convert mild cerulein AP to SAP with greater cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and 100% mortality without affecting AP induction or pancreatic necrosis. Increased pancreatic lipase amounts and activity were noted in the extensive visceral fat necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ failure, and mortality but not the parameters of AP induction. Pancreatic lipase expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP independent of pancreatic necrosis and the inflammatory response. PMID:25579844

  14. RIP Kinase-Mediated Necrosis as an Alternative Mechanism of Photoreceptor Death

    PubMed Central

    Murakami, Yusuke; Miller, Joan W.; Vavvas, Demetrios G.

    2011-01-01

    Photoreceptor cell death is the terminal event in a variety of retinal disorders including age-related macular degeneration, retinitis pigmentosa, and retinal detachment. Apoptosis has been thought to be the major form of cell death in these diseases, however accumulating evidence suggests that another pathway, programmed necrosis is also important. Recent studies have shown that, when caspase pathways are blocked, receptor interacting protein (RIP) kinases promote necrosis and overcome apoptosis inhibition. Therefore, targeting of both caspase and RIP kinase pathways are required for effective photoreceptor protection. Here, we summarize the current knowledge of RIP kinase-mediated necrotic signaling and its contribution to photoreceptor death. PMID:21670490

  15. Skin necrosis after calcium hydroxylapatite injection into the glabellar and nasolabial folds.

    PubMed

    Georgescu, Dan; Jones, Yian; McCann, John D; Anderson, Richard L

    2009-01-01

    Calcium hydroxylapatite-induced skin necrosis occurred in 2 patients after injection in the glabella and the nasolabial fold, respectively. Supportive treatment with oral steroids, nitroglycerin paste, and warm compresses was initiated more than 48 hours after injection, and its role in recovery is uncertain. Both patients underwent microdermabrasion and used hydrocortisone ointment to flatten the scar, which resulted in gradual improvement with a reasonable cosmetic outcome 4 months after injection. This is the first report of calcium hydroxylapatite-induced skin necrosis. Injectors should be aware of this potential adverse event and counsel their patients appropriately.

  16. Classical syndromes in occupational medicine: phosphorus necrosis--a classical occupational disease

    SciTech Connect

    Felton, J.S.

    1982-01-01

    A disease nearly extinct in occupational health history is phosphorus necrosis, previously seen in near-epidemic proportions among workers making phosphorus-containing matches. Similar destructive lesions were encountered early in the 20th century among personnel fabricating fireworks. Through the diligent efforts of an economist and a supportive congressman, legislation was passed in 1912 placing a tax on phosphorus matches, and because of the fiscal burden resulting, a nontoxic substitute for elemental phosphorus was adopted by all manufacturers. Today phosphorus necrosis is extremely rare, but the former presence of the disease points up both apathy and courage in the identification and eradication of a remarkably disfiguring work-caused disease.

  17. Dissecting Cellulitis of the Scalp Responding to Intravenous Tumor Necrosis Factor-alpha Antagonist.

    PubMed

    Wollina, Uwe; Gemmeke, Astrid; Koch, André

    2012-04-01

    The authors present the case of a 30-year-old male patient with a severe and long-standing dissecting cellulitis of the scalp. The disease did not respond to conventional treatment, including oral antibiotics, isotretinoin, and prednisolone. Quality of life was significantly impaired. After introduction of anti-tumor necrosis factor-alpha treatment (infliximab), the malodorous discharge stopped, inflammation was reduced significantly, nodules became flat, and pain decreased. The treatment was well tolerated although he developed a temporary psoriasiform rash after the second intravenous infusion. In conclusion, anti-tumor necrosis factor-alpha treatment is a new therapeutic option in this severe and recalcitrant disorder. PMID:22708007

  18. Dissecting Cellulitis of the Scalp Responding to Intravenous Tumor Necrosis Factor-alpha Antagonist

    PubMed Central

    Wollina, Uwe; Gemmeke, Astrid; Koch, André

    2012-01-01

    The authors present the case of a 30-year-old male patient with a severe and long-standing dissecting cellulitis of the scalp. The disease did not respond to conventional treatment, including oral antibiotics, isotretinoin, and prednisolone. Quality of life was significantly impaired. After introduction of anti-tumor necrosis factor-alpha treatment (infliximab), the malodorous discharge stopped, inflammation was reduced significantly, nodules became flat, and pain decreased. The treatment was well tolerated although he developed a temporary psoriasiform rash after the second intravenous infusion. In conclusion, anti-tumor necrosis factor-alpha treatment is a new therapeutic option in this severe and recalcitrant disorder. PMID:22708007

  19. SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.

    PubMed

    Spiegel, Ronen; Shaag, Avraham; Edvardson, Simon; Mandel, Hanna; Stepensky, Polina; Shalev, Stavit A; Horovitz, Yoseph; Pines, Ophry; Elpeleg, Orly

    2009-09-01

    Four patients, aged 7-20 years, suffered from recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. Using homozygosity mapping, a pathogenic missense mutation in the SLC25A19 gene that encodes the mitochondrial thiamine pyrophosphate transporter was identified. An SLC25A19 mutation was previously reported in Amish congenital lethal microcephaly but the present patients' phenotype is markedly different, with normal head circumference, normal early childhood development, age-appropriate cognitive skills, and normal urinary organic acid profile. Determination of the SLC25A19 sequence should be considered in patients with bilateral striatal necrosis and progressive polyneuropathy. PMID:19798730

  20. Warfarin-induced skin necrosis diagnosed on clinical grounds and treated with maggot debridement therapy.

    PubMed

    Biscoe, Anna Louise; Bedlow, Alison

    2013-01-01

    A patient with a history of deep vein thrombosis presented with painful bruising and blistering on his left leg 7-10 days after warfarin treatment. A complicated 2-month treatment followed, where vasculitis was originally diagnosed from histological findings before the final diagnosis of warfarin-induced skin necrosis (WISN) was made on clinical grounds. Warfarin was stopped, reversed and low molecular weight heparin started but, the lesions had progressed to full thickness necrosis. This was originally treated with conventional surgical debridement before introducing maggot debridement therapy (MDT) in an effort to try to salvage the limb.

  1. Necrosis of the tail of pancreas following proximal splenic artery embolization.

    PubMed

    Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

    2016-01-01

    The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication. PMID:27177891

  2. Alcohol-Dependent Liver Cell Necrosis in vitro: A New Model

    NASA Astrophysics Data System (ADS)

    Schanne, Francis A. X.; Zucker, Amy H.; Farber, John L.; Rubin, Emanuel

    1981-04-01

    In alcoholic liver injury, necrosis is involved in the progression from benign fatty liver to alcoholic hepatitis and cirrhosis. However, there is no practical model of alcohol-dependent liver cell necrosis. The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol. This indicates that some general physical effect of alcohol on cellular membranes renders cells susceptible to otherwise nonlethal injuries. The in vitro model described in this report may thus be used to search for a general mechanism underlying alcohol-related tissue injury.

  3. Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus involving μ-calpain activation.

    PubMed

    Müller, Georg Johannes; Hasseldam, Henrik; Rasmussen, Rune Skovgaard; Johansen, Flemming Fryd

    2014-11-01

    Transient forebrain ischemia (TFI) leads to hippocampal CA1 pyramidal cell death which is aggravated by glucocorticoids (GC). It is unknown how GC affect apoptosis and necrosis in cerebral ischemia. We therefore investigated the co-localization of activated caspase-3 (casp-3) with apoptosis- and necrosis-like cell death morphologies in CA1 of rats treated with dexamethasone prior to TFI (DPTI). In addition, apoptosis- (casp-9, casp-3, casp-3-cleaved PARP and cleaved α-spectrin 145/150 and 120kDa) and necrosis-related (calpain-specific casp-9 cleavage, μ-calpain upregulation and cleaved α-spectrin 145/150kDa) cell death mechanisms were investigated by Western blot analysis. DPTI expedited CA1 neuronal death from day 4 to day 1 and increased the magnitude of CA1 neuronal death from 66.2% to 91.3% at day 7. Furthermore, DPTI decreased the overall (days 1-7) percentage of dying neurons displaying apoptosis-like morphology from 4.7% to 0.3% and, conversely, increased the percentage of neurons with necrosis-like morphology from 95.3% to 99.7%. In animals subjected to TFI without dexamethasone (ischemia-only), 7.4% of all dying CA1 neurons were casp-3-immunoreactive (IR), of which 3.1% co-localized with apoptosis-like and 4.3% with necrosis-like changes. By contrast, DPTI decreased the percentage of dying neurons with casp-3 IR to 1.4%, of which 0.3% co-localized with apoptosis-like changes and 1.1% with necrosis-like changes. Western blot analysis from DPTI animals showed a significant elevation of μ-calpain, a calpain-produced necrosis-related casp-9 fragment (25kDa) and cleavage of α-spectrin into 145/150kDa fragments at day 4, whereas in ischemia-only animals a significant increase of casp-3-cleaved PARP, cleavage of α-spectrin into 145/150 and 120kDa fragments was detected at day 7. We conclude that DPTI, in addition to augmenting and expediting CA1 neuronal death, causes a shift from apoptosis-like cell death to necrosis involving μ-calpain activation.

  4. First Complete Genome Sequence of Bean common mosaic necrosis virus from East Timor

    PubMed Central

    Maina, Solomon; Edwards, Owain R.; de Almeida, Luis; Ximenes, Abel

    2016-01-01

    We present here the first complete Bean common mosaic necrosis virus (BCMNV) genomic sequence isolated from virus-infected common bean (Phaseolus vulgaris) in East Timor, and compare it with six complete BMCNV genomes from the Netherlands, and one each from the United States, Tanzania, and an unspecified country. It most resembled the Netherlands strain NL-8 genome. PMID:27688343

  5. Multiple singing magnet ingestion leading to pressure necrosis of the small bowel

    PubMed Central

    Mirza, M. Bilal; Bux, Nabi; Talat, Nabila; Saleem, Muhammad

    2015-01-01

    Multiple Magnet ingestion may cause a number of sinister complications. We report a case of multiple singing magnets ingestion by a 2-year-old girl resulting in intestinal obstruction and pressure necrosis of the small bowel. A bunch of seven magnets present in the small bowel was removed operatively. PMID:25829675

  6. Bone marrow necrosis at transformation of chronic granulocytic leukaemia treated with interferon.

    PubMed Central

    Kendra, J R; Pickens, S; Singh, A K; Singh, K

    1992-01-01

    A patient with chronic myeloid leukaemia was treated with interferon without using conventional cytotoxic agents. Bone marrow necrosis developed at the onset of blast transformation. It is suggested that cytotoxic drugs should be given before treatment with interferon for chronic myeloid leukaemia. Cytotoxic drugs may also be needed to prevent rapid bone marrow growth once interferon has been withdrawn. PMID:1401221

  7. Progressive outer retinal necrosis: a missed diagnosis and a blind, young woman.

    PubMed

    Parekh, Parth; Oldfield, Edward C; Marik, Paul E

    2013-01-01

    We present a 33-year-old woman with a history significant for HIV/AIDS (CD4 count of 17) and diabetes mellitus who was diagnosed as having progressive outer retinal necrosis (PORN) after presenting with peripheral vision loss. This case provided a diagnostic challenge and demonstrates the devastating effects of a misdiagnosis as it pertains to PORN. PMID:23608868

  8. Structural Biology of Tumor Necrosis Factor Demonstrated for Undergraduates Instruction by Computer Simulation

    ERIC Educational Resources Information Center

    Roy, Urmi

    2016-01-01

    This work presents a three-dimensional (3D) modeling exercise for undergraduate students in chemistry and health sciences disciplines, focusing on a protein-group linked to immune system regulation. Specifically, the exercise involves molecular modeling and structural analysis of tumor necrosis factor (TNF) proteins, both wild type and mutant. The…

  9. Radiation necrosis causing failure of automatic ventilation during sleep with central sleep apnea

    SciTech Connect

    Udwadia, Z.F.; Athale, S.; Misra, V.P.; Wadia, N.H.

    1987-09-01

    A patient operated upon for a midline cerebellar hemangioblastoma developed failure of automatic respiration during sleep, together with central sleep apnea syndrome, approximately two years after receiving radiation therapy to the brain. Clinical and CT scan findings were compatible with a diagnosis of radiation necrosis as the cause of his abnormal respiratory control.

  10. Progressive outer retinal necrosis: a missed diagnosis and a blind, young woman

    PubMed Central

    Parekh, Parth; Oldfield, Edward C; Marik, Paul E

    2013-01-01

    We present a 33-year-old woman with a history significant for HIV/AIDS (CD4 count of 17) and diabetes mellitus who was diagnosed as having progressive outer retinal necrosis (PORN) after presenting with peripheral vision loss. This case provided a diagnostic challenge and demonstrates the devastating effects of a misdiagnosis as it pertains to PORN. PMID:23608868

  11. First Complete Genome Sequence of Bean common mosaic necrosis virus from East Timor.

    PubMed

    Maina, Solomon; Edwards, Owain R; de Almeida, Luis; Ximenes, Abel; Jones, Roger A C

    2016-01-01

    We present here the first complete Bean common mosaic necrosis virus (BCMNV) genomic sequence isolated from virus-infected common bean (Phaseolus vulgaris) in East Timor, and compare it with six complete BMCNV genomes from the Netherlands, and one each from the United States, Tanzania, and an unspecified country. It most resembled the Netherlands strain NL-8 genome. PMID:27688343

  12. Walled-off pancreatic necrosis and other current concepts in the radiological assessment of acute pancreatitis.

    PubMed

    Cunha, Elen Freitas de Cerqueira; Rocha, Manoel de Souza; Pereira, Fábio Payão; Blasbalg, Roberto; Baroni, Ronaldo Hueb

    2014-01-01

    Acute pancreatitis is an inflammatory condition caused by intracellular activation and extravasation of inappropriate proteolytic enzymes determining destruction of pancreatic parenchyma and peripancreatic tissues. This is a fairly common clinical condition with two main presentations, namely, endematous pancreatitis - a less severe presentation -, and necrotizing pancreatitis - the most severe presentation that affects a significant part of patients. The radiological evaluation, particularly by computed tomography, plays a fundamental role in the definition of the management of severe cases, especially regarding the characterization of local complications with implications in the prognosis and in the definition of the therapeutic approach. New concepts include the subdivision of necrotizing pancreatitis into the following presentations: pancreatic parenchymal necrosis with concomitant peripancreatic tissue necrosis, and necrosis restricted to peripancreatic tissues. Moreover, there was a systematization of the terms acute peripancreatic fluid collection, pseudocyst, post-necrotic pancreatic/peripancreatic fluid collections and walled-off pancreatic necrosis. The knowledge about such terms is extremely relevant to standardize the terminology utilized by specialists involved in the diagnosis and treatment of these patients.

  13. Genetics Home Reference: tumor necrosis factor receptor-associated periodic syndrome

    MedlinePlus

    ... Tumor necrosis factor receptor-associated periodic syndrome (TRAPS): definition, semiology, prognosis, pathogenesis, treatment, and place relative to other periodic joint diseases. Joint Bone Spine. 2004 Jul;71(4):284-90. Review. Citation on PubMed Pettersson T, Kantonen J, Matikainen S, ...

  14. Sulfide toxicity: Mechanical ventilation and hypotension determine survival rate and brain necrosis

    SciTech Connect

    Baldelli, R.J.; Green, F.H.Y.; Auer, R.N. )

    1993-09-01

    Occupational exposure to hydrogen sulfide is one of the leading causes of sudden death in the workplace, especially in the oil and gas industry. High-dose exposure causes immediate neurogenic apnea and death; lower doses cause [open quotes]knockdown[close quotes] (transient loss of consciousness, with apnea). Because permanent neurological sequelae have been reported, the authors sought to determine whether sulfide can directly kill central nervous system neurons. Ventilated and unventilated rats were studied to allow administration of higher doses of sulfide and to facilitate physiological monitoring. It was extremely difficult to produce cerebral necrosis with sulfide. Only one of eight surviving unventilated rats given high-dose sulfide (a dose that was lethal in [ge]50% of animals) showed cerebral necrosis. Mechanical ventilation shifted the dose that was lethal in 50% of the animals to 190 mg/kg from 94 mg/kg in the unventilated rats. Sulfide was found to potently depress blood pressure. Cerebral necrosis was absent in the ventilated rats (n = 11), except in one rat that showed profound and sustained hypotension to [le]35 Torr. Electroencephalogram activity ceased during exposure but recovered when the animals regained consciousness. The authors conclude that very-high-dose sulfide is incapable of producing cerebral necrosis by a direct histotoxic effect. 32 refs., 5 figs.

  15. Early Diversification of the Tumor Necrosis Superfamily in Teleosts: Genomic Characterization and Expression Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The tumor necrosis factor superfamily (TNFSF) of proteins are cytokines involved in diverse immunological and developmental pathways. Little is known about their evolution or expression in lower vertebrate species. Bioinformatic searches of Zebrafish, Tetraodon, and Fugu genome and other teleost E...

  16. Heritability of tolerance for infectious hematopoietic necrosis in sockeye salmon (Oncorhynchus nerka)

    USGS Publications Warehouse

    McIntyre, John D.; Amend, Donald F.

    1978-01-01

    A hierarchical breeding design was used to demonstrate the heritability of tolerance for infectious hematopoietic necrosis (IHN) in sockeye salmon. Oncorhynchus nerka. Heritability was about 30%, indicating that artificial selection may increase the number of fish that can tolerate the disease.

  17. Progressive outer retinal necrosis: a missed diagnosis and a blind, young woman.

    PubMed

    Parekh, Parth; Oldfield, Edward C; Marik, Paul E

    2013-04-22

    We present a 33-year-old woman with a history significant for HIV/AIDS (CD4 count of 17) and diabetes mellitus who was diagnosed as having progressive outer retinal necrosis (PORN) after presenting with peripheral vision loss. This case provided a diagnostic challenge and demonstrates the devastating effects of a misdiagnosis as it pertains to PORN.

  18. Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells

    NASA Technical Reports Server (NTRS)

    Plymale, D. R.; Tang, D. S.; Comardelle, A. M.; Fermin, C. D.; Lewis, D. E.; Garry, R. F.

    1999-01-01

    BACKGROUND: Data currently available on HIV-1-induced cytopathology is unclear regarding the mechanism of cell killing. OBJECTIVE: To clarify the extent to which apoptosis or necrosis is involved in HIV-1-induced cell death in view of conflicting existing data. METHODS: T lymphoblastoid cells or peripheral blood mononuclear cells were infected by various strains of HIV-1 and the numbers of apoptotic or necrotic cells were quantified at various times after infection using video-image analysis techniques; the results were compared with the amount of fragmented DNA using a quantitative method. Measurement of mitochondrial transmembrane potential (deltapsi(m)) and intracellular calcium concentrations [Ca2+]i was performed with fluorescent probes and fluorescence concentration analysis (FCA). RESULTS: Although lymphoblastoid and monocytoid cells acutely infected by HIV-1 had increased levels of fragmented DNA, a marker of apoptotic cell death, few (<12%) had condensed chromatin and fragmented nuclei, the morphological features of apoptosis. The predominant alterations in acutely infected cells were distended endoplasmic reticulum and abnormal mitochondria; these ultrastructural changes are consistent with necrosis, although some infected cells simultaneously displayed features of both necrosis and apoptosis. Viability of cells persistently infected by HIV-1 was only minimally reduced from that of uninfected cells. This reduction was accounted for by an increased propensity of the persistently infected cells to die by apoptosis. Alterations in [Ca2+]i and deltapsi(m) occurred in both acutely and persistently infected cells. CONCLUSION: Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells.

  19. Until Death Do Us Part: Necrosis and Oxidation Promote the Tumor Microenvironment

    PubMed Central

    Lotfi, Ramin; Kaltenmeier, Christof; Lotze, Michael T.; Bergmann, Christoph

    2016-01-01

    Summary Tumor proliferation is concomitant with autophagy, limited apoptosis, and resultant necrosis. Necrosis is associated with the release of damage-associated molecular pattern molecules (DAMPs), which act as ‘danger signals’, recruiting inflammatory cells, inducing immune responses, and promoting wound healing. Most of the current treatment strategies for cancer (chemotherapy, radiation therapy, hormonal therapy) promote DAMP release following therapy-induced tumor death by necroptosis and necrosis. Myeloid cells (monocytes, dendritic cells (DCs), and granulocytes), as well as mesenchymal stromal cells (MSCs) belong to the early immigrants in response to unscheduled cell death, initiating and modulating the subsequent inflammatory response. Responding to DAMPs, MSCs, and DCs promote an immunosuppressive milieu, while eosinophils induce oxidative conditions limiting the biologic activity of DAMPs over time and distance. Regulatory T cells are strongly affected by pattern recognition receptor signaling in the tumor microenvironment and limit immune reactivity coordinately with myeloid-derived suppressor cells. Means to ‘aerobically’ oxidize DAMPs provide a novel strategy for limiting tumor progression. The present article summarizes our current understanding of the impact of necrosis on the tumor microenvironment and the influence of oxidative conditions found within this setting. PMID:27226794

  20. Genome mapping of postzygotic hybrid necrosis in an interspecific pear population

    PubMed Central

    Montanari, Sara; Brewer, Lester; Lamberts, Robert; Velasco, Riccardo; Malnoy, Mickael; Perchepied, Laure; Guérif, Philippe; Durel, Charles-Eric; Bus, Vincent G M; Gardiner, Susan E; Chagné, David

    2016-01-01

    Deleterious epistatic interactions in plant inter- and intraspecific hybrids can cause a phenomenon known as hybrid necrosis, characterized by a typical seedling phenotype whose main distinguishing features are dwarfism, tissue necrosis and in some cases lethality. Identification of the chromosome regions associated with this type of incompatibility is important not only to increase our understanding of the evolutionary diversification that led to speciation but also for breeding purposes. Development of molecular markers linked to the lethal genes will allow breeders to avoid incompatible inbred combinations that could affect the expression of important agronomic tratis co-segregating with these genes. Although hybrid necrosis has been reported in several plant taxa, including Rosaceae species, this phenomenon has not been described previously in pear. In the interspecific pear population resulting from a cross between PEAR3 (Pyrus bretschneideri × Pyrus communis) and ‘Moonglow’ (P. communis), we observed two types of hybrid necrosis, expressed at different stages of plant development. Using a combination of previously mapped and newly developed genetic markers, we identified three chromosome regions associated with these two types of lethality, which were genetically independent. One type resulted from a negative epistatic interaction between a locus on linkage group 5 (LG5) of PEAR3 and a locus on LG1 of ‘Moonglow’, while the second type was due to a gene that maps to LG2 of PEAR3 and which either acts alone or more probably interacts with another gene of unknown location inherited from ‘Moonglow’. PMID:26770810

  1. Posterior shoulder dislocation and humeral head necrosis in a recreational scuba diver with diabetes.

    PubMed

    Gorman, D F; Sandow, M J

    1992-11-01

    An insulin-dependent diabetic who was previously a recreational scuba diver suffered a posterior shoulder dislocation after a trivial injury and was subsequently found to have local necrosis of the humeral head. The only definite conclusion that can be reached is that this patient should not dive again.

  2. Tumor necrosis factor alpha gene -376 polymorphism and susceptibility to multiple sclerosis: an Egyptian study.

    PubMed

    Nada, Mona Abd el Fattah; Labib, Dalia Ahmed

    2011-03-01

    Tumor necrosis factor alpha, a proinflammatory cytokine, plays an important role in the clinical activity of relapsing-remitting multiple sclerosis and the development of progression. Dysregulation in the expression of tumor necrosis factor gene had been suggested in the pathogenesis of multiple sclerosis. Our aim was to investigate the relationship between tumor necrosis factor α-376 polymorphism with disease susceptibility and course of multiple sclerosis in Egyptian patients. Polymerase chain reaction and restriction fragment length polymorphism were carried out on 36 primary progressive multiple sclerosis patients, 36 age- and sex-matched remitting relapsing multiple sclerosis patients (diagnosed according to McDonald's Diagnostic criteria) and 30 age- and sex-matched healthy controls. The GG genotype and the guanine allele (G) were detected significantly more often in the primary progressive (p = 0.02; p = 0.004, respectively) and remitting relapsing (p = 0.015; p = 0.024, respectively) multiple sclerosis groups as compared with the healthy control group. The G allele in the examined position in tumor necrosis factor alpha might have a role as regards susceptibility in both remitting relapsing and primary progressive multiple sclerosis.

  3. Proteomic changes in plasma of broiler chickens with femoral head necrosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Femoral head necrosis (FHN) is a skeletal problem in broiler chickens where the proximal femoral head cartilage shows susceptibility to separation from its growth plate. The FHN selected birds showed higher bodyweights and reduced plasma cholesterol. The proteomic differences in the plasma of health...

  4. Colonic necrosis due to calcium polystyrene sulfonate (Kalimate) not suspended in sorbitol.

    PubMed

    Castillo-Cejas, María Dolores; de-Torres-Ramírez, Inés; Alonso-Cotoner, Carmen

    2013-04-01

    Cation-exchange resins are used in the management of hyperkalemia, particularly in patients with end-stage renal disease. These resins were associated with gastrointestinal tract lesions, especially sodium polystyrene sulfonate (Kayexalate) mixed with sorbitol. We present a case of colonic necrosis after the administration of calcium polystyrene sulfonate (Kalimate) not suspended in sorbitol.

  5. Brain necrosis after fractionated radiation therapy: Is the halftime for repair longer than we thought?

    SciTech Connect

    Bender, Edward T.

    2012-11-15

    Purpose: To derive a radiobiological model that enables the estimation of brain necrosis and spinal cord myelopathy rates for a variety of fractionation schemes, and to compare repair effects between brain and spinal cord. Methods: Sigmoidal dose response relationships for brain radiation necrosis and spinal cord myelopathy are derived from clinical data using nonlinear regression. Three different repair models are considered and the repair halftimes are included as regression parameters. Results: For radiation necrosis, a repair halftime of 38.1 (range 6.9-76) h is found with monoexponential repair, while for spinal cord myelopathy, a repair halftime of 4.1 (range 0-8) h is found. The best-fit alpha beta ratio is 0.96 (range 0.24-1.73)Conclusions: A radiobiological model that includes repair corrections can describe the clinical data for a variety of fraction sizes, fractionation schedules, and total doses. Modeling suggests a relatively long repair halftime for brain necrosis. This study suggests that the repair halftime for late radiation effects in the brain may be longer than is currently thought. If confirmed in future studies, this may lead to a re-evaluation of radiation fractionation schedules for some CNS diseases, particularly for those diseases where fractionated stereotactic radiation therapy is used.

  6. Progressive outer retinal necrosis associated with occlusive vasculitis in acquired immunodeficiency syndrome.

    PubMed

    Tseng, Chien-Chi; Chen, San-Ni; Hwang, Jiunn-Feng; Lin, Chun-Ju; Chen, Huan-Sheng

    2015-05-01

    A 45-year-old man, a case of acquired immunodeficiency syndrome, received a highly active antiretroviral therapy at the outpatient service for 4 years without regular follow-up. He experienced progressively blurred vision for 6 months and a cutaneous zoster on his back 3 months ago. He was diagnosed with progressive outer retinal necrosis by polymerase chain reaction-restriction fragment length polymorphism using an aqueous humor sample, which revealed an existence of varicella zoster virus. He was given a combination of systemic, intravitreal antiviral and a highly active antiretroviral therapy. Occlusive vasculitis, an unusual finding for progressive outer retinal necrosis, developed in both eyes 1 week after the secondary intravitreal injection. Unfortunately, his vision deteriorated to no light perception in both eyes within 2 weeks. Progressive outer retinal necrosis is characterized clinically as showing minimal or no inflammation in the aqueous and vitreous humors, absence of retinal vasculitis, and patches of yellowish spots located deep in the retina. Physicians should pay attention to this rare case of progressive outer retinal necrosis associated occlusive vasculitis with very poor prognosis in spite of aggressive treatment.

  7. Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer.

    PubMed

    Chaabane, Wiem; User, Sırma D; El-Gazzah, Mohamed; Jaksik, Roman; Sajjadi, Elaheh; Rzeszowska-Wolny, Joanna; Los, Marek J

    2013-02-01

    Cell death is a fundamental ingredient of life. Thus, not surprisingly more than one form of cell death exists. Several excellent reviews on various forms of cell death have already been published but manuscripts describing interconnection and interdependence between such processes are uncommon. Here, what follows is a brief introduction on all three classical forms of cell death, followed by a more detailed insight into the role of p53, the master regulator of apoptosis, and other forms of cell death. While discussing p53 and also the role of caspases in cell death forms, we offer insight into the interplay between autophagy and apoptosis, or necrosis, where autophagy may initially serve pro-survival functions. The review moves further to present some details about less researched forms of programmed cell death, namely necroptosis, necrosis and mitoptosis. These "mixed" forms of cell death allow us to highlight the interconnected nature of cell death forms, particularly apoptosis and necrosis. The interdependence between apoptosis, autophagy and necrosis, and their significance for cancer development and treatment are also analyzed in further parts of the review. In the concluding parts, the afore-mentioned issues will be put in perspective for the development of novel anti-cancer therapies.

  8. Avascular necrosis of the distal phalangeal epiphysis following physeal fracture: a case report.

    PubMed

    Nissenbaum, M

    1999-05-01

    Avascular necrosis of the distal phalangeal epiphysis following an unrecognized angulated Salter II fracture of the distal phalanx treated by open reduction and internal fixation resulted in premature closure of the growth plate and mild shortening. The epiphysis itself revascularized and good function of the distal interphalangeal joint was maintained.

  9. Partial fingertip necrosis following a digital surgical procedure in a patient with primary Raynaud's phenomenon.

    PubMed

    Uygur, Safak; Tuncer, Serhan

    2014-12-01

    Raynaud's phenomenon is a common clinical disorder consisting of recurrent, long-lasting and episodic vasospasm of the fingers and toes often associated with exposure to cold. In this article, we present a case of partial fingertip necrosis following digital surgical procedure in a patient with primary Raynaud's phenomenon.

  10. Walled-off pancreatic necrosis and other current concepts in the radiological assessment of acute pancreatitis*

    PubMed Central

    Cunha, Elen Freitas de Cerqueira; Rocha, Manoel de Souza; Pereira, Fábio Payão; Blasbalg, Roberto; Baroni, Ronaldo Hueb

    2014-01-01

    Acute pancreatitis is an inflammatory condition caused by intracellular activation and extravasation of inappropriate proteolytic enzymes determining destruction of pancreatic parenchyma and peripancreatic tissues. This is a fairly common clinical condition with two main presentations, namely, endematous pancreatitis - a less severe presentation -, and necrotizing pancreatitis - the most severe presentation that affects a significant part of patients. The radiological evaluation, particularly by computed tomography, plays a fundamental role in the definition of the management of severe cases, especially regarding the characterization of local complications with implications in the prognosis and in the definition of the therapeutic approach. New concepts include the subdivision of necrotizing pancreatitis into the following presentations: pancreatic parenchymal necrosis with concomitant peripancreatic tissue necrosis, and necrosis restricted to peripancreatic tissues. Moreover, there was a systematization of the terms acute peripancreatic fluid collection, pseudocyst, post-necrotic pancreatic/peripancreatic fluid collections and walled-off pancreatic necrosis. The knowledge about such terms is extremely relevant to standardize the terminology utilized by specialists involved in the diagnosis and treatment of these patients. PMID:25741074

  11. Serum chemistry and histopathology of broiler femoral head necrosis and tibial dyschondroplasia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Femoral head necrosis (FHN) and tibial dyschondroplasia (TD) are two major leg problems in young meat type poultry which cause lameness, bone deformity and infections. Whereas FHN results from disarticulation of the femoral growth plate from the articular cartilage, TD lesions are characterized by i...

  12. Binding Mode Analysis of Zerumbone to Key Signal Proteins in the Tumor Necrosis Factor Pathway

    PubMed Central

    Fatima, Ayesha; Abdul, Ahmad Bustamam Hj.; Abdullah, Rasedee; Karjiban, Roghayeh Abedi; Lee, Vannajan Sanghiran

    2015-01-01

    Breast cancer is the second most common cancer among women worldwide. Several signaling pathways have been implicated as causative and progression agents. The tumor necrosis factor (TNF) α protein plays a dual role in promoting and inhibiting cancer depending largely on the pathway initiated by the binding of the protein to its receptor. Zerumbone, an active constituent of Zingiber zerumbet, Smith, is known to act on the tumor necrosis factor pathway upregulating tumour necrosis factor related apoptosis inducing ligand (TRAIL) death receptors and inducing apoptosis in cancer cells. Zerumbone is a sesquiterpene that is able to penetrate into the hydrophobic pockets of proteins to exert its inhibiting activity with several proteins. We found a good binding with the tumor necrosis factor, kinase κB (IKKβ) and the Nuclear factor κB (NF-κB) component proteins along the TNF pathway. Our results suggest that zerumbone can exert its apoptotic activities by inhibiting the cytoplasmic proteins. It inhibits the IKKβ kinase that activates the NF-κB and also binds to the NF-κB complex in the TNF pathway. Blocking both proteins can lead to inhibition of cell proliferating proteins to be downregulated and possibly ultimate induction of apoptosis. PMID:25629232

  13. Genome mapping of postzygotic hybrid necrosis in an interspecific pear population.

    PubMed

    Montanari, Sara; Brewer, Lester; Lamberts, Robert; Velasco, Riccardo; Malnoy, Mickael; Perchepied, Laure; Guérif, Philippe; Durel, Charles-Eric; Bus, Vincent G M; Gardiner, Susan E; Chagné, David

    2016-01-01

    Deleterious epistatic interactions in plant inter- and intraspecific hybrids can cause a phenomenon known as hybrid necrosis, characterized by a typical seedling phenotype whose main distinguishing features are dwarfism, tissue necrosis and in some cases lethality. Identification of the chromosome regions associated with this type of incompatibility is important not only to increase our understanding of the evolutionary diversification that led to speciation but also for breeding purposes. Development of molecular markers linked to the lethal genes will allow breeders to avoid incompatible inbred combinations that could affect the expression of important agronomic tratis co-segregating with these genes. Although hybrid necrosis has been reported in several plant taxa, including Rosaceae species, this phenomenon has not been described previously in pear. In the interspecific pear population resulting from a cross between PEAR3 (Pyrus bretschneideri × Pyrus communis) and 'Moonglow' (P. communis), we observed two types of hybrid necrosis, expressed at different stages of plant development. Using a combination of previously mapped and newly developed genetic markers, we identified three chromosome regions associated with these two types of lethality, which were genetically independent. One type resulted from a negative epistatic interaction between a locus on linkage group 5 (LG5) of PEAR3 and a locus on LG1 of 'Moonglow', while the second type was due to a gene that maps to LG2 of PEAR3 and which either acts alone or more probably interacts with another gene of unknown location inherited from 'Moonglow'. PMID:26770810

  14. MRI brain tumor segmentation and necrosis detection using adaptive Sobolev snakes

    NASA Astrophysics Data System (ADS)

    Nakhmani, Arie; Kikinis, Ron; Tannenbaum, Allen

    2014-03-01

    Brain tumor segmentation in brain MRI volumes is used in neurosurgical planning and illness staging. It is important to explore the tumor shape and necrosis regions at di erent points of time to evaluate the disease progression. We propose an algorithm for semi-automatic tumor segmentation and necrosis detection. Our algorithm consists of three parts: conversion of MRI volume to a probability space based on the on-line learned model, tumor probability density estimation, and adaptive segmentation in the probability space. We use manually selected acceptance and rejection classes on a single MRI slice to learn the background and foreground statistical models. Then, we propagate this model to all MRI slices to compute the most probable regions of the tumor. Anisotropic 3D di usion is used to estimate the probability density. Finally, the estimated density is segmented by the Sobolev active contour (snake) algorithm to select smoothed regions of the maximum tumor probability. The segmentation approach is robust to noise and not very sensitive to the manual initialization in the volumes tested. Also, it is appropriate for low contrast imagery. The irregular necrosis regions are detected by using the outliers of the probability distribution inside the segmented region. The necrosis regions of small width are removed due to a high probability of noisy measurements. The MRI volume segmentation results obtained by our algorithm are very similar to expert manual segmentation.

  15. Ceramide-induced formation of ROS and ATP depletion trigger necrosis in lymphoid cells.

    PubMed

    Villena, Joan; Henriquez, Mauricio; Torres, Vicente; Moraga, Francisco; Díaz-Elizondo, Jessica; Arredondo, Cristian; Chiong, Mario; Olea-Azar, Claudio; Stutzin, Andres; Lavandero, Sergio; Quest, Andrew F G

    2008-03-15

    In lymphocytes, Fas activation leads to both apoptosis and necrosis, whereby the latter form of cell death is linked to delayed production of endogenous ceramide and is mimicked by exogenous administration of long- and short-chain ceramides. Here molecular events associated with noncanonical necrotic cell death downstream of ceramide were investigated in A20 B lymphoma and Jurkat T cells. Cell-permeable, C6-ceramide (C6), but not dihydro-C6-ceramide (DH-C6), induced necrosis in a time- and dose-dependent fashion. Rapid formation of reactive oxygen species (ROS) within 30 min of C6 addition detected by a dihydrorhodamine fluorescence assay, as well as by electron spin resonance, was accompanied by loss of mitochondrial membrane potential. The presence of N-acetylcysteine or ROS scavengers like Tiron, but not Trolox, attenuated ceramide-induced necrosis. Alternatively, adenovirus-mediated expression of catalase in A20 cells also attenuated cell necrosis but not apoptosis. Necrotic cell death observed following C6 exposure was associated with a pronounced decrease in ATP levels and Tiron significantly delayed ATP depletion in both A20 and Jurkat cells. Thus, apoptotic and necrotic death induced by ceramide in lymphocytes occurs via distinct mechanisms. Furthermore, ceramide-induced necrotic cell death is linked here to loss of mitochondrial membrane potential, production of ROS, and intracellular ATP depletion. PMID:18191646

  16. Carbohydrate and ethane release with Erwinia carotovora subspecies betavasculorum--induced necrosis.

    PubMed

    Kuykendall, L David; Hunter, William J

    2008-02-01

    Erwinia carotovora subspecies betavasculorum, also known as E. betavasculorum and Pectobacterium betavasculorum, is a soil bacterium that has the capacity to cause root rot necrosis of sugarbeets. The qualitatively different pathogenicity exhibited by the virulent E. carotovora strain and two avirulent strains, a Citrobacter sp. and an Enterobacter cloacae, was examined using digital analysis of photographic evidence of necrosis as well as for carbohydrate, ethane, and ethylene release compared with uninoculated potato tuber slices. Visual scoring of necrosis was superior to digital analysis of photographs. The release of carbohydrates and ethane from potato tuber slices inoculated with the soft rot necrosis-causing Erwinia was significantly greater than that of potato tuber slices that had not been inoculated or that had been inoculated with the nonpathogenic E. cloacae and Citrobacter sp. strains. Interestingly, ethylene production from potato slices left uninoculated or inoculated with the nonpathogenic Citrobacter strain was 5- to 10-fold higher than with potato slices inoculated with the pathogenic Erwinia strain. These findings suggest that (1) carbohydrate release might be a useful measure of the degree of pathogenesis, or relative virulence; and that (2) bacterial suppression of ethylene formation may be a critical step in root rot disease formation.

  17. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis.

    PubMed

    Figarella-Branger, Dominique; Mokhtari, Karima; Colin, Carole; Uro-Coste, Emmanuelle; Jouvet, Anne; Dehais, Caroline; Carpentier, Catherine; Villa, Chiara; Maurage, Claude-Alain; Eimer, Sandrine; Polivka, Marc; Vignaud, Jean-Michel; Laquerriere, Annie; Sevestre, Henri; Lechapt-Zalcman, Emmanuelle; Quintin-Roué, Isabelle; Aubriot-Lorton, Marie-Hélène; Diebold, Marie-Danièle; Viennet, Gabriel; Adam, Clovis; Loussouarn, Delphine; Michalak, Sophie; Rigau, Valérie; Heitzmann, Anne; Vandenbos, Fanny; Forest, Fabien; Chiforeanu, Danchristian; Tortel, Marie-Claire; Labrousse, François; Chenard, Marie-Pierre; Nguyen, Anh Tuan; Varlet, Pascale; Kemeny, Jean Louis; Levillain, Pierre-Marie; Cazals-Hatem, Dominique; Richard, Pomone; Delattre, Jean-Yves

    2015-07-01

    Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO. PMID:25407774

  18. Lipopolysaccharide triggers invasive streptococcal disease in mice through a tumour necrosis factor-alpha-dependent mechanism.

    PubMed

    Diao, Hongyan; Kohanawa, Masashi; Yimin; Nakajima, Hirofumi; Sato, Yuichiro; Minagawa, Tomonori; Nakane, Akio

    2002-03-01

    Streptococcus pyogenes sometimes induces invasive streptococcal infection, including streptococcal toxic shock syndrome (STSS). Muscular necrosis is one of the peculiar symptoms of invasive streptococcal infection and STSS. We inoculated S. pyogenes into the muscles of mice. To do so, 5 x 10(8) bacteria in 0.2 ml phosphate-buffered saline were injected into the right hind thigh. None of the mice injected with the bacteria showed muscular necrosis and none died. Tumour necrosis factor-alpha (TNF-alpha) and infiltration of leucocytes were detected in the muscles of infected sites, although the condition of the infected mice did not deteriorate after anti-TNF-alpha monoclonal antibody treatment. The infected mice treated intraperitoneally with Escherichia coli lipopolysaccharide (LPS) showed augmentation of bacterial growth, muscular necrosis and death. TNF-alpha was detected in the sera of the infected mice treated with LPS, but not in the muscles of the infected sites. Infiltration of leucocytes into the infected muscle was not observed in the infected mice treated with LPS. Anti-TNF-alpha monoclonal antibody treatment decreased mortality in the infected mice treated with LPS. Moreover, the infected mice treated with recombinant TNF-alpha showed augmentation of muscular necrosis and death. These results suggest that systemic production of TNF-alpha induced by stimulation with LPS inhibits infiltration of leucocytes into the infected site and exacerbates muscular infection, and that TNF-alpha produced in streptococcal infection is not a defence factor for the host. Invasive streptococcal infection and STSS appear to be induced by both S. pyogenes and the host's immune system.

  19. Mechanism of chlorogenic acid treatment on femoral head necrosis and its protection of osteoblasts

    PubMed Central

    ZHANG, MINGJUAN; HU, XIANDA

    2016-01-01

    The aim of the present study was to investigate the therapeutic effect of chlorogenic acid on hormonal femoral head necrosis and its protection of osteoblasts. The study established a femoral head necrosis model in Wistar rats using Escherichia coli endotoxin and prednisolone acetate. The rats were divided into five groups and were treated with different concentrations of chlorogenic acid (1, 10 and 20 mg/kg). The main detected indicators were the blood rheology, bone mineral density, and the hydroxyproline and hexosamine (HOM) contents. At a cellular level, osteoblasts were cultured and treated by drug-containing serum. Subsequently, cell proliferation and the osteoblast cycle were measured using flow cytometry, and the protein expression levels of Bax and B-cell lymphoma 2 (Bcl-2) were detected using western blotting. Chlorogenic acid at a concentration of 20 mg/kg (high-dose) enhanced the bone mineral density of the femoral head and femoral neck following ischemia. Simultaneously, blood flow following the injection of prednisolone acetate was significantly improved, and the HOM contents of the high-dose chlorogenic acid group were significantly different. The results from the flow cytometry analysis indicated that chlorogenic acid can efficiently ameliorate hormone-induced necrosis. The osteoblasts were isolated and cultured. The MTT colorimetric assay showed that chlorogenic acid at different densities can increase the proliferation capabilities of osteoblasts and accelerate the transition process of G0/G1 phase to S phase, as well as enhance mitosis and the regeneration of osteoblasts. Western blotting detection indicated that chlorogenic acid may prohibit the decrease of Bcl-2 and the increase of Bax during apoptosis, thereby inhibiting osteoblast apoptosis and preventing the deterioration of femoral head necrosis. In conclusion, chlorogenic acid at the density of 20 mg/kg is effective in the treatment of hormonal femoral head necrosis, which may be

  20. Carbamate pesticide-induced apoptosis and necrosis in human natural killer cells.

    PubMed

    Li, Q; Kobayashi, M; Kawada, T

    2014-01-01

    We previously found that ziram, a carbamate fungicide, significantly induced apoptosis and necrosis in human NK-92MI, a natural killer cell line. To investigate whether other carbamate pesticides also induce apoptosis and necrosis in human natural killer cell, we conducted further experiments with NK-92CI, a human natural killer cell line using a more sensitive assay. NK-92CI cells were treated with ziram, thiram, maneb or carbaryl at 0.031-40 microM for 2-24 h in the present study. Apoptosis and necrosis were determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspases 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that ziram and thiram also induced apoptosis and necrosis in a time- and dose-dependent manner; however, maneb and carbaryl induced apoptosis and necrosis only at higher doses in NK-92CI cells. The strength of the apoptosis-inducing effect differed among the pesticides, and the order was as follows: thiram > ziram greater than maneb greater than carbaryl. NK-92CI was more sensitive to ziram than NK-92MI. Moreover, ziram and thiram significantly increased the intracellular level of active caspase 3 in NK-92CI and caspase inhibitor significantly inhibited the apoptosis. Ziram and thiram significantly caused mitochondrial cytochrome-c release in NK-92CI. These findings indicate that carbamate pesticides can induce apoptosis in natural killer cells, and the apoptosis is mediated by both the caspase-cascade and mitochondrial cytochrome-c pathways.

  1. Macrophage response in patients diagnosed with aseptic necrosis of the femoral head presenting different risk factors.

    PubMed

    Kamal, Diana; Trăistaru, Rodica; Kamal, Constantin Kamal; Alexandru, Dragoş Ovidiu; Ion, Daniela Adriana; Grecu, Dan Cristian

    2015-01-01

    Aseptic necrosis of the femoral head is a condition caused by partial or total interruption of blood supply to the femoral head. The diminished blood supply causes necrosis of the cellular elements and of the bone marrow, followed by the collapse of the bone structure, events that ultimately lead to the destruction of the bone tissue, the appearance of local pain and loss of function in the affected coxofemoral joint. The importance of this condition is that it mainly affects young adults aged 30-50 years, active from a socio-professional standpoint, and increased life expectancy. The material studied to achieve CD68 immunostaining was represented by bone fragments from the area of necrosis and from the adjacent areas of the femoral heads, harvested from 39 patients when performing hip arthroplasty surgery. The patients were diagnosed with aseptic necrosis of the femoral head and hospitalized in the Clinic of Orthopedics and Traumatology, Emergency County Hospital of Craiova, Romania, from June 2014 to January 2015. The 39 patients included in the study were divided into four categories according to presented risk factors (alcohol, alcohol and smoking, trauma, corticosteroids). All the 39 cases had positive immunostaining for CD68, macrophage being highlighted both in the area of necrosis and in the adjacent areas. We noted significant differences in the number and arrangement of macrophages in patients presenting different risk factors. The highest number of macrophages was present in patients presenting a risk factor corticosteroids, and the lowest number of macrophages was found in patients who had trauma as the main risk factor.

  2. A novel Fizzy/Cdc20-dependent mechanism suppresses necrosis in neural stem cells

    PubMed Central

    Kuang, Chaoyuan; Golden, Krista L.; Simon, Claudio R.; Damrath, John; Buttitta, Laura; Gamble, Caitlin E.; Lee, Cheng-Yu

    2014-01-01

    Cancer stem cells likely survive chemotherapy or radiotherapy by acquiring mutations that inactivate the endogenous apoptotic machinery or by cycling slowly. Thus, knowledge about the mechanisms linking the activation of an alternative cell death modality and the cell cycle machinery could have a transformative impact on the development of new cancer therapies, but the mechanisms remain completely unknown. We investigated the regulation of alternative cell death in Drosophila larval brain neural stem cells (neuroblasts) in which apoptosis is normally repressed. From a screen, we identified two novel loss-of-function alleles of the Cdc20/fizzy (fzy) gene that lead to premature brain neuroblast loss without perturbing cell proliferation in other diploid cell types. Fzy is an evolutionarily conserved regulator of anaphase promoting complex/cyclosome (APC/C). Neuroblasts carrying the novel fzy allele or exhibiting reduced APC/C function display hallmarks of necrosis. By contrast, neuroblasts overexpressing the non-degradable form of canonical APC/C substrates required for cell cycle progression undergo mitotic catastrophe. These data strongly suggest that Fzy can elicit a novel pro-survival function of APC/C by suppressing necrosis. Neuroblasts experiencing catastrophic cellular stress, or overexpressing p53, lose Fzy expression and undergo necrosis. Co-expression of fzy suppresses the death of these neuroblasts. Consequently, attenuation of the Fzy-dependent survival mechanism functions downstream of catastrophic cellular stress and p53 to eliminate neuroblasts by necrosis. Strategies that target the Fzy-dependent survival mechanism might lead to the discovery of new treatments or complement the pre-existing therapies to eliminate apoptosis-resistant cancer stem cells by necrosis. PMID:24598157

  3. SU-E-T-549: Modeling Relative Biological Effectiveness of Protons for Radiation Induced Brain Necrosis

    SciTech Connect

    Mirkovic, D; Peeler, C; Grosshans, D; Titt, U; Taleei, R; Mohan, R

    2015-06-15

    Purpose: To develop a model of the relative biological effectiveness (RBE) of protons as a function of dose and linear energy transfer (LET) for induction of brain necrosis using clinical data. Methods: In this study, treatment planning information was exported from a clinical treatment planning system (TPS) and used to construct a detailed Monte Carlo model of the patient and the beam delivery system. The physical proton dose and LET were computed in each voxel of the patient volume using Monte Carlo particle transport. A follow-up magnetic resonance imaging (MRI) study registered to the treatment planning CT was used to determine the region of the necrosis in the brain volume. Both, the whole brain and the necrosis volumes were segmented from the computed tomography (CT) dataset using the contours drawn by a physician and the corresponding voxels were binned with respect to dose and LET. The brain necrosis probability was computed as a function of dose and LET by dividing the total volume of all necrosis voxels with a given dose and LET with the corresponding total brain volume resulting in a set of NTCP-like curves (probability as a function of dose parameterized by LET). Results: The resulting model shows dependence on both dose and LET indicating the weakness of the constant RBE model for describing the brain toxicity. To the best of our knowledge the constant RBE model is currently used in all clinical applications which may Result in increased rate of brain toxicities in patients treated with protons. Conclusion: Further studies are needed to develop more accurate brain toxicity models for patients treated with protons and other heavy ions.

  4. Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies

    NASA Astrophysics Data System (ADS)

    Privalov, Valeriy A.; Lappa, Alexander V.; Bigbov, Elmir N.

    2011-02-01

    A photodynamic therapy experiment on 118 inbred white mice with transplanted Ehrlich's tumor (mouse mammary gland adenocarcinoma) is performed to reveal mechanisms of necrosis formation. In 7-10 days the tumor of 1-1.5 cm diameter is formed under skin at the injection point, and PDT procedure is applied. There were used a chlorine type photosensitizer RadachlorineTM and 662 nm wavelength diode laser. The drug is injected by intravenously at the dose of 40 mg/kg; the irradiation is executed in 2-2.5 hours at the surface dose of about 200 J/cm2. Each of the mice had a photochemical reaction in form of destructive changes at the irradiation region with subsequent development of dry coagulation necrosis. After rejection of the necrosis there occurred epithelization of defect tissues in a tumor place. Histological investigations were conducted in different follow-up periods, in 5 and 30 min, 1, 3, 6, and 12 hours, 1, 3, 7 and 28 days after irradiation. They included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that an important role in damaging mechanisms of photodynamic action belongs to hypoxic injuries of tumor mediated by micro vascular disorders and blood circulatory disturbances. The injuries are formed in a few stages: microcirculation angiospasm causing vessel paresis, irreversible stases in capillaries, diapedetic hemorrhages, thromboses, and thrombovasculitis. It is marked mucoid swelling and fibrinoid necrosis of vascular tissue. Progressive vasculitises result in total vessel obliteration and tumor necrosis.

  5. Comparison of the effects of troxerutin and heparinoid on flap necrosis.

    PubMed

    Celik, Alper; Ersoy, Omer F; Ozkan, Namik; Kayaoglu, Huseyin A; Ozugurlu, Fikret; Cakir, Ebru A; Lordlar, Nese; Omeroglu, Suna

    2010-05-01

    We aimed to assess the effects of local troxerutin and heparinoid (HEP) treatments in a model of flap necrosis. Three groups of Wistar albino rats, each comprising 10 animals were used. A cranially based 6x3-cm full-thickness random-pattern skin flap was raised and sutured to the same area in each model. The control group was treated daily with normal saline, the second with topical HEP and the third with topical troxerutin. The amount of flap necrosis was measured in all groups by the end of the seventh day. Flap tissues were excised for histological analysis and evaluation of the expression of vascular endothelial growth factor (VEGF) levels. Assessment of the blood levels of nitric oxide was also performed in each animal by cardiac puncture. The mean area of flap necrosis was 110.6mm(2) in the control, 39.44 mm(2) in the troxerutin and 47.11 mm(2) in the heparinoid-treated rats. The treatment arms exhibited significant reduction in areas of flap necrosis, compared with the control group (p<0.001), but it was similar among treatment groups (p=0.60). The rates of fibroblast proliferation were decreased in control group as compared to HEP and troxerutin arms (p<0.001). The mean level of collagen density, collagen organisation, granulation tissue and demarcation were similar in all rats. Measurement of VEGF expression did not show any significant difference between the groups (p=0.30). Nitric oxide levels were significantly higher in control rats, as compared to treatment groups (p<0.0001), but were similar in treatment arms (p=0.45). Our results suggest that troxerutin and HEP effectively reduce the flap necrosis and improve flap survival. The observed effects might be due to their anti-oedematogenic, radical-scavenging, antioxidant effects and supportive activities on capillary permeability and transudation.

  6. Synergistic Interactions with a High Intraoperative Expander Fill Volume Increase the Risk for Mastectomy Flap Necrosis

    PubMed Central

    Khavanin, Nima; Jordan, Sumanas; Lovecchio, Francis; Fine, Neil A.

    2013-01-01

    Purpose Prosthetic-based breast reconstruction is performed with increasing frequency in the United States. Major mastectomy skin flap necrosis is a significant complication with outcomes ranging from poor aesthetic appearance to reconstructive failure. The present study aimed to explore the interactions between intraoperative fill and other risk factors on the incidence of flap necrosis in patients undergoing mastectomy with immediate expander/implant-based reconstruction. Methods A retrospective review of 966 consecutive patients (1,409 breasts) who underwent skin or nipple sparing mastectomy with immediate tissue expander reconstruction at a single institution was conducted. Age, body mass index, hypertension, smoking status, premastectomy and postmastectomy radiation, acellular dermal matrix use, and application of the tumescent mastectomy technique were analyzed as potential predictors of flap necrosis both independently and as synergistic variables with high intraoperative fill. The following three measures of interaction were calculated: relative excess risk due to interaction, attributable proportion of risk due to interaction, and synergy index (SI). Results Intraoperative tissue expander fill volume was high (≥66.7% of the maximum volume) in 40.9% (576 of 1,409 breasts) of cases. The unadjusted flap necrosis rate was greater in the high intraoperative fill cohort than in the low fill cohort (10.4% vs. 7.1%, p=0.027). Multivariate logistic regression did not identify high intraoperative fill volume as an independent risk factor for flap necrosis (odds ratio 1.442, 95% confidence interval 0.973-2.137, p=0.068). However, four risk factors were identified that interacted significantly with intraoperative fill volume, namely tumescence, age, hypertension, and obesity. The SI, or the departure from additive risks, was largest for tumescence (SI, 25.3), followed by hypertension (SI, 2.39), obesity (SI, 2.28), and age older than 50 years (SI, 1.17). Conclusion

  7. Bacillus thuringiensis Crystal Protein Cry6Aa Triggers Caenorhabditis elegans Necrosis Pathway Mediated by Aspartic Protease (ASP-1)

    PubMed Central

    Zhang, Fengjuan; Peng, Donghai; Cheng, Chunsheng; Zhou, Wei; Ju, Shouyong; Wan, Danfeng; Yu, Ziquan; Shi, Jianwei; Deng, Yaoyao; Wang, Fenshan; Ye, Xiaobo; Hu, Zhenfei; Lin, Jian; Ruan, Lifang; Sun, Ming

    2016-01-01

    Cell death plays an important role in host-pathogen interactions. Crystal proteins (toxins) are essential components of Bacillus thuringiensis (Bt) biological pesticides because of their specific toxicity against insects and nematodes. However, the mode of action by which crystal toxins to induce cell death is not completely understood. Here we show that crystal toxin triggers cell death by necrosis signaling pathway using crystal toxin Cry6Aa-Caenorhabditis elegans toxin-host interaction system, which involves an increase in concentrations of cytoplasmic calcium, lysosomal lyses, uptake of propidium iodide, and burst of death fluorescence. We find that a deficiency in the necrosis pathway confers tolerance to Cry6Aa toxin. Intriguingly, the necrosis pathway is specifically triggered by Cry6Aa, not by Cry5Ba, whose amino acid sequence is different from that of Cry6Aa. Furthermore, Cry6Aa-induced necrosis pathway requires aspartic protease (ASP-1). In addition, ASP-1 protects Cry6Aa from over-degradation in C. elegans. This is the first demonstration that deficiency in necrosis pathway confers tolerance to Bt crystal protein, and that Cry6A triggers necrosis represents a newly added necrosis paradigm in the C. elegans. Understanding this model could lead to new strategies for nematode control. PMID:26795495

  8. [Total upper lip necrosis and loxoscelism caused by violin spider bite].

    PubMed

    Bogdán, Sándor; Barabás, József; Zacher, Gábor; Huszár, Tamás; Velich, Norbert; Szabó, György; Németh, Zsolt

    2005-11-01

    Arthropods and in particular spiders are a common embodiment of our fears, despite the fact that only a few species are dangerous to man. The authors present a case involving severe local and general reactions to a loxosceles (brown recluse spider) bite. They give an overview of the occurrence of loxosceles spiders, the signs and symptoms of envenomation and the therapeutic possibilities. The severe symptoms presenting following loxosceles envenomation is termed loxoscelism. Loxoscelism is characterised by local soft tissue necrosis of varying degree at the site of the sting, and rarely, life-threatening general reactions, such as haemolysis with ensuing anaemia, and renal failure. Therapeutic interventions following loxosceles bites range from dapsone treatment to hyperbaric oxygen therapy, but the most promising therapy is the use of the antiserum, commercially available in certain South-American countries where loxosceles bites are common. Treatment of soft tissue necrosis consists of necrectomy and surgical reconstruction following the resolution of the inflammatory symptoms. PMID:16304811

  9. Tetraodon nigroviridis as a nonlethal model of infectious spleen and kidney necrosis virus (ISKNV) infection

    SciTech Connect

    Xu Xiaopeng; Huang Lichao; Weng Shaoping; Wang Jing; Lin Ting; Tang Junliang; Li Zhongsheng; Lu Qingxia; Xia Qiong; Yu Xiaoqiang; He Jianguo

    2010-10-25

    Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. We have previously established a high mortality ISKNV infection model of zebrafish (Danio rerio). In this study, a nonlethal Tetraodon nigroviridis model of ISKNV infection was established. ISKNV infection did not cause lethal disease in Tetraodon but could infect almost all the organs of this species. Electron microscopy showed ISKNV particles were present in infected tissues. Immunofluorescence and quantitative real-time PCR analysis showed that nearly all the virions and infected cells were cleared at 14 d postinfection. The expression profiles of interferon-{gamma} and tumor necrosis factor-{alpha} gene in response to ISKNV infection were significantly different in Tetraodon and zebrafish. The establishment of the nonlethal Tetraodon model of ISKNV infection can offer a valuable tool complementary to the zebrafish infection model for studying megalocytivirus disease, fish immune systems, and viral tropism.

  10. Papillary Necrosis in Rats Caused by Aspirin and Aspirin-containing Mixtures

    PubMed Central

    Nanra, Ranjit S.; Kincaid-Smith, Priscilla

    1970-01-01

    Nearly half the rats gavage-fed with aspirin and aspirin-containing mixtures developed papillary necrosis in 20 weeks. This incidence is similar to that found in rats on A.P.C. mixtures with high and low concentrations of p-chloracetanilide, an impurity of phenacetin. Aspirin alone produced necrosis in 7 out of 19 rats (36·8%) whereas phenacetin in the same dose had failed to cause any renal damage over six to nine months. If these results also apply to man they suggest that aspirin and not phenacetin may be the major factor in analgesic nephropathy in patients taking A.P.C. mixtures. An augmented clearance of aspirin appeared to afford some protection to the medulla, and it is suggested that this observation may have important clinical and epidemiological applications. Imagesp560-a PMID:5454357

  11. Tumor necrosis factor alpha gene expression in human monocytic THP-1 cells exposed to beryllium.

    PubMed

    Galbraith, G M; Pandey, J P; Schmidt, M G; Arnaud, P; Goust, J M

    1996-01-01

    Chronic beryllium disease, which results from occupational exposure to particulate beryllium, is characterized by the development of lung granulomas and progressive pulmonary fibrosis. Increased production of proinflammatory cytokines (e.g., tumor necrosis factor alpha and interleukin-1 beta) by pulmonary alveolar macrophages occurs in many chronic fibrotic lung diseases and is thought to contribute to the disease process. The purpose of the present study was to investigate cytokine production by human monocytic cells exposed to beryllium in vitro. The results indicated that such cells respond to beryllium ions in the presence of fluoride by accumulation of messenger ribonucleic acid for both tumor necrosis factor alpha and interleukin-1 beta. These findings suggest that inhaled beryllium may directly stimulate the production of these cytokines by alveolar macrophages in vitro. PMID:8629860

  12. Artificial transmission to and susceptibility of Puget Sound fish to viral erythrocytic necrosis (VEN)

    USGS Publications Warehouse

    MacMillian, John R.; Mulcahy, Dan

    1979-01-01

    In Puget Sound, Wash., the incidence of viral erythrocytic necrosis (VEN) varied geographically from 0 to 17% in chum salmon (Oncorhynchus keta) and from 4 to 59% in Pacific herring (Clupea harengus pallasi). The disease was experimentally transmitted by intraperitoneal injection to chum, pink (O. gorbuscha), coho (O. kisutch), chinook (O. tshawytscha), sockeye (O. nerka), and Atlantic (Salmo salar) salmon, and rainbow (S. gairdneri), brown (S. trutta), and brook (Salvelinus fontinalis) trout. The disease was transmitted to chum salmon and brook trout by waterborne virus. Virus obtained from herring was experimentally transmitted into chum salmon by intraperitoneal injection. Key words: viral erythrocytic necrosis, fish disease, transmission

  13. Tumor Necrosis Factor Receptor 2: Its Contribution to Acute Cellular Rejection and Clear Cell Renal Carcinoma

    PubMed Central

    Wang, Jun; Al-Lamki, Rafia S.

    2013-01-01

    Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein and one of the two receptors that orchestrate the complex biological functions of tumor necrosis factor (TNF, also designed TNF-α). Accumulating experimental evidence suggests that TNFR2 plays an important role in renal disorders associated with acute cellular rejection and clear cell renal carcinoma but its exact role in these settings is still not completely understood. This papers reviews the factors that may mediate TNFR2 induction in acute cellular rejection and clear cell renal carcinoma and its contribution to these conditions and discusses its therapeutic implications. A greater understanding of the function of TNFR2 may lead to the development of new anti-TNF drugs. PMID:24350291

  14. Subtotal tongue necrosis in delayed diagnosed giant-cell arteritis: a case report.

    PubMed

    Biebl, Matthias Oliver; Hugl, Beate; Posch, Lydia; Tzankov, Alexandar; Weber, Florian; Perkmann, Reinhold; Fraedrich, Gustav

    2004-01-01

    Giant-cell arteritis (GCA) is a chronic systemic vasculitis of large- and medium-sized vessels, mainly affecting elderly patients. Headache, vision impairment, jaw claudication, and scalp tenderness are common symptoms. However, diagnosis can be difficult because GCA can affect almost every vascular pathway and lead to a variety of possible manifestations. We report the case of a belated diagnosed GCA, resulting in nearly complete necrosis of the mobile part of the tongue, visual impairment, and neurologic as well as intestinal ischemic symptoms. Aggressive immunosuppressive treatment resolved the symptoms, but the patient remained severely morbid because of bilateral necrosis of the mobile part of the tongue. In any case of unclear ischemic symptoms in an elderly patient, one must keep GCA in mind as the possible culprit disease.

  15. Tissue Necrosis Monitoring for HIFU Ablation with T1 Contrast MRI Imaging

    NASA Astrophysics Data System (ADS)

    Hwang, San-Chao; Yao, Ching; Kuo, Ih-Yuan; Tsai, Wei-Cheng; Chang, Hsu

    2011-09-01

    In MR-guided HIFU ablation, MTC (Magnetization Transfer Contrast) or perfusion imaging is usually used after ablation to evaluate the ablated area based on the thermally induced necrosis contrast. In our MR-guided HIFU ablation study, a T1 contrast MRI scan sequence has been used to distinguish between necrotic and non-necrotic tissue. The ablation of porcine meat in-vitro and in-vivo pig leg muscle show that the necrotic area of T1 contrast MRI image coincides with the photographs of sliced specimen. The sequence is considerably easier to apply than MTC or perfusion imaging, while giving good necrosis contrast. In addition, no injection of contrast agent is needed, allowing multiple scans to be applied throughout the entire ablation procedure.

  16. An Unusual Cause of Acute Upper Gastrointestinal Bleeding: Acute Esophageal Necrosis

    PubMed Central

    Tokala, Madhusudhan R.; Dhillon, Sonu; Pisoh, Watcoun-Nchinda; Walayat, Saqib; Vanar, Vishwas; Puli, Srinivas R.

    2016-01-01

    Acute esophageal necrosis (AEN), also called “black esophagus,” is a condition characterized by circumferential necrosis of the esophagus with universal distal involvement and variable proximal extension with clear demarcation at the gastroesophageal junction. It is an unusual cause of upper gastrointestinal bleeding and is recognized with distinct and striking mucosal findings on endoscopy. The patients are usually older and are critically ill with shared comorbidities, which include atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, chronic renal insufficiency, and malnutrition. Alcoholism and substance abuse could be seen in younger patients. Patients usually have systemic hypotension along with upper abdominal pain in the background of clinical presentation of hematemesis and melena. The endoscopic findings confirm the diagnosis and biopsy is not always necessary unless clinically indicated in atypical presentations. Herein we present two cases with distinct clinical presentation and discuss the endoscopic findings along with a review of the published literature on the management of AEN. PMID:27642529

  17. Classical syndromes in occupational medicine: Phosphorus necrosis--a classical occupational disease.

    PubMed

    Felton, J S

    1982-01-01

    A disease nearly extinct in occupational health history is phosphorus necrosis, previously seen in near-epidemic proportions among workers making phosphorus-containing matches. Similar destructive lesions were encountered early in the 20th century among personnel fabricating fireworks. Through the diligent efforts of an economist and a supportive congressman, legislation was passed in 1912 placing a tax on phosphorus matches, and because of the fiscal burden resulting, a nontoxic substitute for elemental phosphorus was adopted by all manufacturers. Today phosphorus necrosis is extremely rare, but the former presence of the disease points up both apathy and courage in the identification and eradication of a remarkably disfiguring work-caused disease. PMID:6751076

  18. Acute cortical necrosis following renal transplantation in a case of sickle cell trait

    PubMed Central

    Shiradhonkar, S.; Jha, R.; Rao, B. S.; Narayan, G.; Sinha, S.; Swarnalata, G.

    2011-01-01

    Renal transplant recipients who have sickle cell disease are at risk of infection, recurrent graft disease, and sickling crisis that affects the long-term outcome. We report a patient of sickle cell trait who developed patchy cortical necrosis in the perioperative period but had a good long-term outcome. The renal cortical necrosis was presumed to be secondary to cyclosporine-basiliximab interaction in the backdrop of sickling trait. The patient additionally had spontaneous closure of vascular access and severe hypertension immediately following transplantation suggestive of vaso-occlusive crisis. Cyclosporine and basiliximab drug interaction needs to be recognized and steps need to be taken in patients to avoid perioperative graft dysfunction. PMID:22022093

  19. A locus on chromosome 7 determines myocardial cell necrosis and calcification (dystrophic cardiac calcinosis) in mice.

    PubMed Central

    Ivandic, B T; Qiao, J H; Machleder, D; Liao, F; Drake, T A; Lusis, A J

    1996-01-01

    Dystrophic cardiac calcinosis, an age-related cardiomyopathy that occurs among certain inbred strains of mice, involves myocardial injury, necrosis, and calcification. Using a complete linkage map approach and quantitative trait locus analysis, we sought to identify genetic loci determining dystrophic cardiac calcinosis in an F2 intercross of resistant C57BL/6J and susceptible C3H/HeJ inbred strains. We identified a single major locus, designated Dyscalc, located on proximal chromosome 7 in a region syntenic with human chromosomes 19q13 and 11p15. The statistical significance of Dyscalc (logarithm of odds score 14.6) was tested by analysis of permuted trait data. Analysis of BxH recombinant inbred strains confirmed the mapping position. The inheritance pattern indicated that this locus influences susceptibility of cells both to enter necrosis and to subsequently undergo calcification. Images Fig. 1 Fig. 3 PMID:8643601

  20. Bacteroides fragilis induce necrosis on mice peritoneal macrophages: In vitro and in vivo assays

    SciTech Connect

    Vieira, J.M.B.D.; Seabra, S.H.; Vallim, D.C.; Americo, M.A.; Fracallanza, S.E.L.; Vommaro, R.C.; Domingues, R.M.C.P.

    2009-10-02

    Bacteroides fragilis is an anaerobic bacteria component of human intestinal microbiota and agent of infections. In the host B. fragilis interacts with macrophages, which produces toxic radicals like NO. The interaction of activated mice peritoneal macrophages with four strains of B. fragilis was evaluated on this study. Previously was shown that such strains could cause metabolic and morphologic alterations related to macrophage death. In this work propidium iodide staining showed the strains inducing macrophage necrosis in that the labeling was evident. Besides nitroblue tetrazolium test showed that B. fragilis stimulates macrophage to produce oxygen radicals. In vivo assays performed in BalbC mice have results similar to those for in vitro tests as well as scanning electron microscopy, which showed the same surface pore-like structures observed in vitro before. The results revealed that B. fragilis strains studied lead to macrophage death by a process similar to necrosis.

  1. Spinal cord infarction in giant cell arteritis associated with scalp necrosis.

    PubMed

    Mustafa, Khader N; Hadidy, Azmy; Joudeh, Anwar; Obeidat, Fatima Nouri; Abdulfattah, Khalid W

    2015-02-01

    Spinal cord infarction is extremely rare in patients with giant cell arteritis (GCA). There are only four case reports in the literature. We describe a 65-year-old man who presented with sudden paraplegia and back pain of 4-days duration with sensory loss below the umbilicus and bilateral scalp necrosis. Magnetic resonance imaging finding was consistent with dorsal spinal cord infarction. Biopsy of the temporal artery confirmed the diagnosis of GCA. The patient was treated with high dose of corticosteroids, which resulted in healing of the scalp ulcerations in 3 weeks, but the paraplegia was irreversible. To our knowledge, this is the first report of spinal cord infarction and simultaneous occurrence of bilateral scalp necrosis in a histopathologically proven GCA. Although literature about spinal cord involvement in GCA is very limited, cord infarction is associated with high mortality and therapeutic challenges since little is understood regarding the pathogenesis that leads to infarction.

  2. Hepatic Necrosis and Degenerative Myopathy Associated with Cassava Feeding in Pigs

    PubMed Central

    Daniel-Igwe, Gloria

    2014-01-01

    Forty-three deaths were recorded among pigs fed boiled cassava meal at a private piggery over a period of two years. There were signs of sudden death in some cases with blood exuding from the external nares, vomiting, muscular weakness and pain or reluctance to move, emaciation, and stunted growth. The necropsy lesions included skeletal and cardiac muscle degeneration and necrosis, icterus, hepatic necrosis, and oedema of the dependent parts. The deaths and clinical signs are thought to be due to a non cyanide toxic principle in cassava, possibly the coumarins (scopoletin), which is found in high levels in cassava diet even after heat treatment. Therefore, the use of proper processing technology to obtain cassava products of high quality is recommended. PMID:26464937

  3. Does phosphodiesterase inhibition lessen facial flap necrosis in tobacco cigarette users?

    PubMed

    Pfaff, Miles; Shah, Ajul; Steinbacher, Derek

    2014-02-01

    Tobacco cigarette smoking remains a serious risk factor for necrosis of local facial skin flaps. To date, no pharmacological therapies exist for cigarette smoke-induced impairment of skin flap tissue survival. Accumulating evidence suggest that phosphodiesterase-5 (PDE-5) inhibitor therapy may counteract the negative effects of cigarette smoke on flap survival. Here, we evaluate skin flap survival in a series of consecutive tobacco cigarette users treated with the PDE-5 inhibitor, sildenafil, who underwent local flap facial reconstruction. We included 11 patients (5 females; median age: 64) with a significant smoking history. Seventeen facial flaps were performed for 14 defects. All patients received sildenafil in the postoperative setting. One complication of necrosis of the flap distal margin was encountered. Follow-up was available for all patients. Our results demonstrate that facial reconstruction in tobacco cigarette smokers can be performed with improved success and that sildenafil therapy may mitigate the deleterious effects of smoking on flap survival. PMID:24488644

  4. An Unusual Cause of Acute Upper Gastrointestinal Bleeding: Acute Esophageal Necrosis

    PubMed Central

    Tokala, Madhusudhan R.; Dhillon, Sonu; Pisoh, Watcoun-Nchinda; Walayat, Saqib; Vanar, Vishwas; Puli, Srinivas R.

    2016-01-01

    Acute esophageal necrosis (AEN), also called “black esophagus,” is a condition characterized by circumferential necrosis of the esophagus with universal distal involvement and variable proximal extension with clear demarcation at the gastroesophageal junction. It is an unusual cause of upper gastrointestinal bleeding and is recognized with distinct and striking mucosal findings on endoscopy. The patients are usually older and are critically ill with shared comorbidities, which include atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, chronic renal insufficiency, and malnutrition. Alcoholism and substance abuse could be seen in younger patients. Patients usually have systemic hypotension along with upper abdominal pain in the background of clinical presentation of hematemesis and melena. The endoscopic findings confirm the diagnosis and biopsy is not always necessary unless clinically indicated in atypical presentations. Herein we present two cases with distinct clinical presentation and discuss the endoscopic findings along with a review of the published literature on the management of AEN.

  5. An Unusual Cause of Acute Upper Gastrointestinal Bleeding: Acute Esophageal Necrosis.

    PubMed

    Kalva, Nikhil R; Tokala, Madhusudhan R; Dhillon, Sonu; Pisoh, Watcoun-Nchinda; Walayat, Saqib; Vanar, Vishwas; Puli, Srinivas R

    2016-01-01

    Acute esophageal necrosis (AEN), also called "black esophagus," is a condition characterized by circumferential necrosis of the esophagus with universal distal involvement and variable proximal extension with clear demarcation at the gastroesophageal junction. It is an unusual cause of upper gastrointestinal bleeding and is recognized with distinct and striking mucosal findings on endoscopy. The patients are usually older and are critically ill with shared comorbidities, which include atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, chronic renal insufficiency, and malnutrition. Alcoholism and substance abuse could be seen in younger patients. Patients usually have systemic hypotension along with upper abdominal pain in the background of clinical presentation of hematemesis and melena. The endoscopic findings confirm the diagnosis and biopsy is not always necessary unless clinically indicated in atypical presentations. Herein we present two cases with distinct clinical presentation and discuss the endoscopic findings along with a review of the published literature on the management of AEN. PMID:27642529

  6. Detection of red-spotted grouper nervous necrosis virus by loop-mediated isothermal amplification.

    PubMed

    Xu, Hai-Dong; Feng, Juan; Guo, Zhi-Xun; Ou, You-Jun; Wang, Jiang-Yong

    2010-01-01

    Red-spotted grouper nervous necrosis virus (RGNNV) causes high mortality in marine fish larvae cultured in China. To control better an outbreak of this virus, a rapid, specific and sensitive detection method based on loop-mediated isothermal amplification (LAMP) was developed. A set of four primers, two outer and two inner, was designed from RGNNV genome RNA. The LAMP reaction mix was optimized. The method was specific as no cross-reaction was observed between white spot syndrome virus, koi herpesvirus, infectious spleen and kidney necrosis virus, mud crab reovirus, and grass carp hemorrhage virus. The sensitivity of LAMP was 100-fold higher than the nested PCR in detecting the presence of RGNNV. RGNNV was detected in the brain of Trachinotus ovatus that showed typical symptoms of NNV infection, with the standardized LAMP procedure.

  7. Complete spontaneous necrosis of hepatocellular carcinoma confirmed on resection: A case report

    PubMed Central

    Saito, Ryusuke; Amano, Hironobu; Abe, Tomoyuki; Fujikuni, Nobuaki; Nakahara, Masahiro; Yonehara, Shuji; Teramen, Kazushi; Noriyuki, Toshio

    2016-01-01

    Introduction Complete spontaneous necrosis of hepatocellular carcinoma (HCC) without any pretreatment or angiography is rare. We present a rare case of spontaneous complete necrosis of HCC, as confirmed after hepatectomy. Presentation of case The patient, a 74-year-old man with a history of alcoholic hepatitis, was referred to our hospital for confirmation of suspected HCC. In March 2015, abdominal ultrasonography detected a low echoic mass in segment 8 (S8) of the liver. Contrast-enhanced computed tomography (CT) imaging revealed interval growth of this tumor and showed that the tumor was well enhanced in the arterial phase and washed out in the portal and delayed phases. The serum alpha-fetoprotein level was elevated at 30.8 ng/mL and the percentage of the L3 isoform was 25.5%. Two months later, CT imaging showed that the tumor was of low density and had decreased in size; no contrast enhancement of the tumor was seen. Spontaneous necrosis of the HCC was considered; however, as we could not exclude viable malignant cells in the tumor, we performed S8 segmentectomy of the liver. The resected tumor specimen had a thick fibrous capsule. Histopathological findings showed only granulation and necrotic tissue accompanied by bleeding and hemosiderosis. No viable tumor cells were observed. The serum alpha-fetoprotein level returned to the normal range one month after surgery. Discussion If spontaneous regression has occurred, there is a possibility of HCC recurrence and of remnant viable tumor cells. Conclusion We present a rare case of complete spontaneous necrosis of HCC and strongly recommended surgical intervention. PMID:27060644

  8. Good visual outcome in an immunocompromised patient with bilateral acute retinal necrosis syndrome: A case report

    PubMed Central

    Marrocos de Aragão, Ricardo E.; Barreira, Ieda M.A.; Arrais, Barbara L.A.; Pereira, Leidiane A.; Ramos, Carine S.

    2013-01-01

    Acute retinal necrosis (ARN) is an uncommon necrotizing, fulminant retinopathy caused by the herpes simplex virus types 1 or 2 or by the varicella zoster vírus with visually devastating consequences. Generally it occurs in patients who are systemically healthy, but occasionally occurs in immunocompromised host. We report a case of bilateral ARN in a patient with AIDS with a good final visual outcome. PMID:25278806

  9. Cytomegalovirus implicated in a case of progressive outer retinal necrosis (PORN).

    PubMed

    Sfeir, Maroun

    2015-08-01

    Progressive outer retinal necrosis, also known as PORN, has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with acquired immune deficiency syndrome (AIDS). Although the etiologic organism has been reported to be Varicella-zoster virus, cytomegalovirus (CMV) can be an etiologic agent. Our case illustrates the occurrence of two opportunistic infections: PORN associated with CMV and Mycobacterium avium intracellulare duodenitis in a patient with uncontrolled HIV infection. PMID:26209386

  10. Colon Necrosis Due to Sodium Polystyrene Sulfonate with and without Sorbitol: An Experimental Study in Rats

    PubMed Central

    Ayoub, Isabelle; Oh, Man S.; Gupta, Raavi; McFarlane, Michael; Babinska, Anna; Salifu, Moro O.

    2015-01-01

    Introduction Based on a single rat study by Lillemoe et al, the consensus has been formed to implicate sorbitol rather than sodium polystyrene sulfonate (SPS) as the culprit for colon necrosis in humans treated with SPS and sorbitol. We tested the hypothesis that colon necrosis by sorbitol in the experiment was due to the high osmolality and volume of sorbitol rather than its chemical nature. Methods 26 rats underwent 5/6 nephrectomy. They were divided into 6 groups and given enema solutions under anesthesia (normal saline, 33% sorbitol, 33% mannitol, SPS in 33% sorbitol, SPS in normal saline, and SPS in distilled water). They were sacrificed after 48 hours of enema administration or earlier if they were very sick. The gross appearance of the colon was visually inspected, and then sliced colon tissues were examined under light microscopy. Results 1 rat from the sorbitol and 1 from the mannitol group had foci of ischemic colonic changes. The rats receiving SPS enema, in sorbitol, normal saline, distilled water, had crystal deposition with colonic necrosis and mucosal erosion. All the rats not given SPS survived until sacrificed at 48 h whereas 11 of 13 rats that received SPS in sorbitol, normal saline or distilled water died or were clearly dying and sacrificed sooner. There was no difference between sorbitol and mannitol when given without SPS. Conclusions In a surgical uremic rat model, SPS enema given alone or with sorbitol or mannitol seemed to cause colon necrosis and high mortality rate, whereas 33% sorbitol without SPS did not. PMID:26413782

  11. K1 and K3 capsular antigens of Klebsiella induce tumor necrosis factor activities.

    PubMed

    Choy, Y M; Tsang, S F; Kong, S K; Leung, K N; Parolis, H; Lee, C Y; Fung, K P

    1996-01-01

    Capsular polysaccharide antigens isolated from Klebsiella pneumoniae sero-type 1 (K1) and sero-type 3 (K3) could induce tumor necrosis factor-alpha in ICR mice. K1 and K3 capsular antigens were found to be non-toxic by brine shrimp bioassay. When injected into Ehrlich ascites tumor-bearing mice, both K1 and K3 capsular antigens exhibited significant suppression in the growth of tumor cells. The significance of these observations is discussed.

  12. Ghrelin protects musculocutaneous tissue from ischemic necrosis by improving microvascular perfusion.

    PubMed

    Rezaeian, F; Wettstein, R; Scheuer, C; Bäumker, K; Bächle, A; Vollmar, B; Menger, M D; Harder, Y

    2012-02-01

    Persistent ischemia in musculocutaneous tissue may lead to wound breakdown and necrosis. The objective of this experimental study was to analyze, whether the gastric peptide ghrelin prevents musculocutaneous tissue from necrosis and to elucidate underlying mechanisms. Thirty-two C57BL/6 mice equipped with a dorsal skinfold chamber containing ischemic musculocutaneous tissue were allocated to four groups: 1) ghrelin; 2) N(ω)-nitro-l-arginine methyl ester (l-NAME); 3) ghrelin and l-NAME; and 4) control. Microcirculation, inflammation, angiogenesis, and tissue survival were assessed by fluorescence microscopy. Inducible and endothelial nitric oxide synthase (iNOS I and eNOS), vascular endothelial growth factor (VEGF), as well as nuclear factor κB (NF-κB) were assessed by Western blot analysis. Ghrelin-treated animals showed an increased expression of iNOS and eNOS in critically perfused tissue compared with controls. This was associated with arteriolar dilation, increased arteriolar perfusion, and a sustained functional capillary density. Ghrelin further upregulated NF-κB and VEGF and induced angiogenesis. Finally, ghrelin reduced microvascular leukocyte-endothelial cell interactions, apoptosis, and overall tissue necrosis (P < 0.05 vs. control). Inhibition of nitric oxide by l-NAME did not affect the anti-inflammatory and angiogenic action of ghrelin but completely blunted the ghrelin-induced tissue protection by abrogating the arteriolar dilation, the improved capillary perfusion, and the increased tissue survival. Ghrelin prevents critically perfused tissue from ischemic necrosis. Tissue protection is the result of a nitric oxide synthase-mediated improvement of the microcirculation but not due to induction of angiogenesis or attenuation of inflammation. This might represent a promising, noninvasive, and clinically applicable approach to protect musculocutaneous tissue from ischemia. PMID:22159999

  13. Cytomegalovirus implicated in a case of progressive outer retinal necrosis (PORN).

    PubMed

    Sfeir, Maroun

    2015-08-01

    Progressive outer retinal necrosis, also known as PORN, has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with acquired immune deficiency syndrome (AIDS). Although the etiologic organism has been reported to be Varicella-zoster virus, cytomegalovirus (CMV) can be an etiologic agent. Our case illustrates the occurrence of two opportunistic infections: PORN associated with CMV and Mycobacterium avium intracellulare duodenitis in a patient with uncontrolled HIV infection.

  14. Ischaemic distal limb necrosis and Klebsiella pneumoniae infection associated with arterial catheterisation in a cat.

    PubMed

    Bowlt, Kelly L; Bortolami, Elisa; Harley, Ross; Murison, Pamela; Wallace, Adrian

    2013-12-01

    This case report describes dorsal pedal arterial thrombosis and infection with Klebsiella pneumoniae subsequent to arterial catheter placement in a cat. The complication led to avascular necrosis of the metatarsal and pedal soft tissue. The catheter was placed for blood pressure monitoring during surgery for correction of a peritoneopericardial diaphragmatic hernia. The exact mechanism of thrombosis was unclear. Amputation of the limb was required and the histopathological findings are presented. This is the first report of such a complication.

  15. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    SciTech Connect

    Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.; Clarke, Joanna I.; Gholami, Parviz; Li, Feng; Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson; Fan, Fang; Jenkins, Rosalind E.; Park, B. Kevin; Hagenbuch, Bruno; Olyaee, Mojtaba; Jaeschke, Hartmut

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  16. Bilateral avascular necrosis of the femoral head due to the use of heroin: A case report

    PubMed Central

    Ozkunt, Okan; Sarıyılmaz, Kerim; Sungur, Mustafa; Ilen, Ferhat; Dikici, Fatih

    2015-01-01

    Introduction Femoral head avascular necrosis is caused by disruption of the blood supply of the femoral head, which finally results in hip dysfunction. Non traumatic osteonecrosis may related with corticosteroid use, alcohol abuse, SLE, hemoglobinopathies or exposure to cytotoxic agents. But avascular necrosis of the femoral head (ANFH) due to heroin use is a rare condition. We report a patient with bilateral ANFH due to heroin use treated by simultaneous bilateral hip arthroplasty. Presentation of case 37 year-old male patient presented with bilateral hip pain that had been occurring for four years. The patient had no history of smoking, excessive drinking, using corticosteroid and the other drugs or trauma but used heroin for 10 years. In clinic and radiologic examination indicated advanced degenerative changes on both hip due to femoral head avascular necrosis. The patient was treated with simultaneous bilateral total hip arthroplasty. After 6 months postoperatively the active hip range of motion was painless. Discussion Avascular femoral head necrosis caused by the using of heroin is rare. Ultimately, osteonecrosis of the femoral head occurs through one final common pathway, which is decreased blood flow to the femoral head that leads bone ischemia and death. But it is still unknown that heroin’s systemic effects. Intravenous drug use more as a serious problem for today. There is a need for comprehensive studies to demonstrate effects of heroin on bone and vascularity metabolism. Conclusion Heroin use will be important problem for population. That’s why is crucial to understand the effect of heroin. PMID:26595896

  17. Magnetic Resonance Imaging of Therapy-Induced Necrosis Using Gadolinium-Chelated Polyglutamic Acids

    SciTech Connect

    Jackson, Edward F.; Esparza-Coss, Emilio; Wen Xiaoxia; Ng, Chaan S.; Daniel, Sherita L.; Price, Roger E.; Rivera, Belinda; Charnsangavej, Chusilp; Gelovani, Juri G.; Li Chun . E-mail: cli@di.mdacc.tmc.edu

    2007-07-01

    Purpose: Necrosis is the most common morphologic alteration found in tumors and surrounding normal tissues after radiation therapy or chemotherapy. Accurate measurement of necrosis may provide an early indication of treatment efficacy or associated toxicity. The purpose of this report is to evaluate the selective accumulation of polymeric paramagnetic magnetic resonance (MR) contrast agents-gadolinium p-aminobenzyl-diethylenetriaminepentaacetic acid-poly(glutamic acid) (L-PG-DTPA-Gd and D-PG-DTPA-Gd)-in necrotic tissue. Methods and Materials: Two different solid tumor models, human Colo-205 xenograft and syngeneic murine OCA-1 ovarian tumors, were used in this study. Necrotic response was induced by treatment with poly(L-glutamic acid)-paclitaxel conjugate (PG-TXL). T{sub 1}-weighted spin-echo images were obtained immediately and up to 4 days after contrast injection and compared with corresponding histologic specimens. Two low-molecular-weight contrast agents, DTPA-Gd and oligomeric(L-glutamic acid)-DTPA-Gd, were used as nonspecific controls. Results: Initially, there was minimal tumor enhancement after injection of either L-PG-DTPA-Gd or D-PG-DTPA-Gd, but rapid enhancement after injection of low-molecular-weight agents. However, polymeric contrast agents, but not low-molecular-weight contrast agents, caused sustained enhancement in regions of tumor necrosis in both tumors treated with PG-TXL and untreated tumors. These data indicate that high molecular weight, rather than in vivo biodegradation, is necessary for the specific localization of polymeric MR contrast agents to necrotic tissue. Moreover, biotinylated L-PG-DTPA-Gd colocalized with macrophages in the tumor necrotic areas, suggesting that selective accumulation of L- and D-PG-DTPA-Gd in necrotic tissue was mediated through residing macrophages. Conclusions: Our data suggest that MR imaging with PG-DTPA-Gd may be a useful technique for noninvasive characterization of treatment-induced necrosis.

  18. Gemella morbillorum Bacteremia after Anti-Tumor Necrosis Factor Alpha as Acne Inversa Therapy

    PubMed Central

    Vossen, Matthias G.; Gattringer, Klaus B.; Khalifeh, Neda; Koreny, Maria; Spertini, Verena; Mallouhi, Ammar; Willeit, Markus; Volc-Platzer, Beatrix; Asboth, Friederike; Graninger, Wolfgang; Thalhammer, Florian

    2012-01-01

    We present a case of fever, brain abscesses, and Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha (TNF-α) therapy in a 21-year-old acne inversa patient currently taking long-term dapsone. To the best of our knowledge, this is the first report describing such a case. During antimicrobial therapy, the patient developed systemic varicella infection with severe thrombocytopenia. PMID:22189120

  19. Complete Genome Sequence of Nervous Necrosis Virus Isolated from Sevenband Grouper (Epinephelus septemfasciatus) in South Korea

    PubMed Central

    Kim, Jong-Oh; Kim, Wi-Sik; Cho, Jae-Kwon; Kim, Kyong-Min; Son, Maeng-Hyun

    2014-01-01

    The draft genome sequence of the nervous necrosis virus (NNV) SGYeosu08, isolated from sevenband grouper (Epinephelus septemfasciatus) in Yeosu, South Korea, was cloned and analyzed. The full-length RNA1 was a 3,103-nucleotide-encoding region of RNA-dependent RNA polymerase, and the RNA2 encoding a coat protein was 1,433 nucleotides in length. This genome sequence might be useful in the development of an accurate diagnostic tool. PMID:25502666

  20. Unexpected radiation laryngeal necrosis after carbon ion therapy using conventional dose fractionation for laryngeal cancer.

    PubMed

    Demizu, Yusuke; Fujii, Osamu; Nagano, Fumiko; Terashima, Kazuki; Jin, Dongcun; Mima, Masayuki; Oda, Naoharu; Takeuchi, Kaoru; Takeda, Makiko; Ito, Kazuyuki; Fuwa, Nobukazu; Okimoto, Tomoaki

    2015-11-01

    Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy.

  1. Management of infected pancreatic necrosis-the "step up" approach and minimal access retroperitoneal pancreatic necrosectomy.

    PubMed

    John, B Joseph; Swaminathan, S; VenkataKrishnan, L; Singh, G S; Krishnaveni, G; Mohandas, N; Pandey, S; Devanand, B

    2015-04-01

    Infected pancreatic necrosis (IPN) is associated with high morbidity and mortality. It is increasingly being recognized that noninvasive management, radiological guided drainage, and minimally invasive procedures rather than the traditionally advocated open necrosectomy are associated with a better outcome in IPN. We present a patient with IPN who was managed with the now popular "step up" approach and describe the procedure of Minimal access retroperitoneal pancreatic necrosectomy. PMID:25972670

  2. Successful treatment of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) with tocilizumab: A case report

    PubMed Central

    Akasbi, Nessrine; Soyfoo, Muhammad S.

    2015-01-01

    Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory disease linked to chromosome 12p13 and, more specifically, with mutations within the tumor necrosis factor receptor superfamily, member 1A gene (TNFRSF1A gene). It is characterized by the presence of fever, abdominal pain, myalgia, arthralgia or arthritis, and skin rash. In this report, we describe the case of a patient with tumor necrosis factor receptor-associated periodic syndrome (TRAPS) treated successfully with the anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody tocilizumab, while treatment with anti-TNF α etanercept and infliximab had both failed.

  3. Avascular necrosis of the hamate: three cases and review of the literature.

    PubMed

    Peters, Sebastian J; Verstappen, C; Degreef, Ilse; Smet, Luc De

    2014-11-01

    Background Avascular necrosis of the hamate (hamate-AVN) is a seldom reported disease of which little is known on etiology, best treatment modalities, and outcome. Hamate-AVN can occur in multiple locations within the hamate. Case Description Case one was an 8-year-old girl with painful AVN of the hamate hook. Surgical excision of the hook was performed, leading to excellent results (follow-up 8 years). Case two was a 44-year-old man with hamate-AVN of the proximal pole surgically treated with a vascularized bone graft from the radius based on the fifth extensor compartment artery, leading to excellent results (follow-up 7 years). Case three was a 36-year-old woman with hamate-AVN of the proximal pole surgically treated with débridement and cancellous bone grafting, leading to poor results (follow-up 1 year). Literature Review Nine other cases of avascular necrosis of the hamate were found in literature, all but one treated surgically. Etiology, treatment, and results of these cases, combined with our own cases, are reviewed. Clinical Relevance This article summarizes and synthesizes all presented cases of avascular necrosis of the hamate. We hope this will be helpful to physicians in decision making when confronted with this rare entity. Level of Evidence 4.

  4. Immunity to Rice Blast Disease by Suppression of Effector-Triggered Necrosis.

    PubMed

    Wang, Ruyi; Ning, Yuese; Shi, Xuetao; He, Feng; Zhang, Chongyang; Fan, Jiangbo; Jiang, Nan; Zhang, Yu; Zhang, Ting; Hu, Yajun; Bellizzi, Maria; Wang, Guo-Liang

    2016-09-26

    Hemibiotrophic pathogens are some of the most destructive plant pathogens, causing huge economic losses and threatening global food security. Infection with these organisms often involves an initial biotrophic infection phase, during which the pathogen spreads in host tissue asymptomatically, followed by a necrotrophic phase, during which host-cell death is induced. How hemibiotrophic pathogens trigger host necrosis and how plants inhibit the transition from the biotrophic stage to the necrotrophic stage in disease symptom expression are mainly unknown. The rice blast fungus Magnaporthe oryzae spreads in rice biotrophically early during infection, but this biotrophic stage is followed by a pronounced switch to cell death and lesion formation. Here, we show that the M. oryzae effector AvrPiz-t interacts with the bZIP-type transcription factor APIP5 in the cytoplasm and suppresses its transcriptional activity and protein accumulation at the necrotrophic stage. Silencing of APIP5 in transgenic rice leads to cell death, and the phenotype is enhanced by the expression of AvrPiz-t. Conversely, Piz-t interacts with and stabilizes APIP5 to prevent necrosis at the necrotrophic stage. At the same time, APIP5 is essential for Piz-t stability. These results demonstrate a novel mechanism for the suppression of effector-triggered necrosis at the necrotrophic stage by an NLR receptor in plants.

  5. Detection of Infectious Pancreatic Necrosis Virus from the Leeches Hemiclepsis marginata and Hirudo medicinalis.

    PubMed

    Salimi, Behnam; Abdi, Kazem

    2016-12-01

    Leeches have been reported to harbor several important fish pathogens, including spring viremia of carp virus, infectious hematopoietic necrosis virus (IHNV), and viral hemorrhagic septicemia virus (VHSV), and also may contain blood protozoa. In the present study, leeches were collected from water bodies located in Kurdistan province, Iran. The specimens were tested for IHNV, VHSV, and infectious pancreatic necrosis virus (IPNV) using the PCR method. The results showed that two different species of leeches, Hemiclepsis marginata and Hirudo medicinalis, were infected by IPNV among the seven species studied. The infected leeches were found in areas that were polluted with untreated sewage coming from upstream fish farms culturing Rainbow Trout Oncorhynchus mykiss. In addition, the fish at fish farms in the vicinity had been infected with IPNV 9 months previously. Our results showed that the virus causing infectious pancreatic necrosis is present in the leeches H. marginata and H. medicinalis, suggesting that leeches are a potential source of IPNV in fish farms. Received October 14, 2015; accepted June 1, 2016. PMID:27687675

  6. Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion.

    PubMed

    You, Bo Ra; Shin, Hye Rim; Han, Bo Ram; Kim, Suhn Hee; Park, Woo Hyun

    2015-02-01

    Auranofin (Au), an inhibitor of thioredoxin reductase, is a known anti‑cancer drug. In the present study, the anti‑growth effect of Au on HeLa cervical cancer cells was examined in association with levels of reactive oxygen species (ROS) and glutathione (GSH). Au inhibited the growth of HeLa cells with an IC50 of ~2 µM at 24 h. This agent induced apoptosis and necrosis, accompanied by the cleavage of poly (ADP‑ribose) polymerase and loss of mitochondrial membrane potential. The pan‑caspase inhibitor, benzyloxycarbonyl‑Val‑Ala‑Asp‑fluoromethylketone, prevented apoptotic cell death and each of the assessed caspase inhibitors inhibited necrotic cell death induced by Au. With respect to the levels of ROS and GSH, Au increased intracellular O2•- in the HeLa cells and induced GSH depletion. The pan‑caspase inhibitor reduced the levels of O2•- and GSH depletion in Au‑treated HeLa cells. The antioxidant, N‑acetyl cysteine, not only attenuated apoptosis and necrosis in the Au‑treated HeLa cells, but also decreased the levels of O2•- and GSH depletion in the cells. By contrast, L‑buthionine sulfoximine, a GSH synthesis inhibitor, intensified cell death O2•- and GSH depletion in the Au‑treated HeLa cells. In conclusion, Au induced apoptosis and necrosis in HeLa cells via the induction of oxidative stress and the depletion of GSH.

  7. Bacterial Delivery of Staphylococcus aureus α-Hemolysin Causes Regression and Necrosis in Murine Tumors

    PubMed Central

    St. Jean, Adam T; Swofford, Charles A; Panteli, Jan T; Brentzel, Zachary J; Forbes, Neil S

    2014-01-01

    Bacterial therapies, designed to manufacture therapeutic proteins directly within tumors, could eliminate cancers that are resistant to other therapies. To be effective, a payload protein must be secreted, diffuse through tissue, and efficiently kill cancer cells. To date, these properties have not been shown for a single protein. The gene for Staphylococcus aureus α-hemolysin (SAH), a pore-forming protein, was cloned into Escherichia coli. These bacteria were injected into tumor-bearing mice and volume was measured over time. The location of SAH relative to necrosis and bacterial colonies was determined by immunohistochemistry. In culture, SAH was released and killed 93% of cancer cells in 24 hours. Injection of SAH-producing bacteria reduced viable tissue to 9% of the original tumor volume. By inducing cell death, SAH moved the boundary of necrosis toward the tumor edge. SAH diffused 6.8 ± 0.3 µm into tissue, which increased the volume of affected tissue from 48.6 to 3,120 µm3. A mathematical model of molecular transport predicted that SAH efficacy is primarily dependent on colony size and the rate of protein production. As a payload protein, SAH will enable effective bacterial therapy because of its ability to diffuse in tissue, kill cells, and expand tumor necrosis. PMID:24590046

  8. Relationship between Active Oxygen Species, Lipid Peroxidation, Necrosis, and Phytoalexin Production Induced by Elicitins in Nicotiana.

    PubMed Central

    Rusterucci, C.; Stallaert, V.; Milat, M. L.; Pugin, A.; Ricci, P.; Blein, J. P.

    1996-01-01

    Excised leaves of Nicotiana tabacum var Xanthi and Nicotiana rustica were treated with cryptogein and capsicein, basic and acidic elicitins, respectively. Both compounds induced leaf necrosis, the intensity of which depended on concentration and duration of treatment. N. tabacum var Xanthi was the most sensitive species and cryptogein was the most active elicitin. Lipid peroxidation in elicitin-treated Nicotiana leaves was closely correlated with the appearance of necrosis. Elicitin treatments induced a rapid and transient burst of active oxygen species (AOS) in cell cultures of both Nicotiana species, with the production by Xanthi cells being 6-fold greater than that by N. rustica. Similar maximum AOS production levels were observed with both elicitins, but capsicein required 10-fold higher concentrations than those of cryptogein. Phytoalexin production was lower in response to both elicitins in N. tabacum var Xanthi cells than in N. rustica cells, and capsicein was the most efficient elicitor of this response. In cryptogein-treated cell suspensions, phytoalexin synthesis was unaffected by diphenyleneiodonium, which inhibited AOS generation, nor was it affected by tiron or catalase, which suppressed AOS accumulation in the extracellular medium. These results suggest that AOS production, lipid peroxidation, and necrosis are directly related, whereas phytoalexin production depends on neither the presence nor the intensity of these responses. PMID:12226334

  9. A tissue engineering strategy for the treatment of avascular necrosis of the femoral head

    PubMed Central

    Aarvold, A.; Smith, J.O.; Tayton, E.R.; Jones, A.M.H.; Dawson, J.I.; Lanham, S.; Briscoe, A.; Dunlop, D.G.; Oreffo, R.O.C.

    2013-01-01

    Background & purpose Skeletal stem cells (SSCs) and impaction bone grafting (IBG) can be combined to produce a mechanically stable living bone composite. This novel strategy has been translated to the treatment of avascular necrosis of the femoral head. Surgical technique, clinical follow-up and retrieval analysis data of this translational case series is presented. Methods SSCs and milled allograft were impacted into necrotic bone in five femoral heads of four patients. Cell viability was confirmed by parallel in vitro culture of the cell-graft constructs. Patient follow-up was by serial clinical and radiological examination. Tissue engineered bone was retrieved from two retrieved femoral heads and was analysed by histology, microcomputed tomography (μCT) and mechanical testing. Results Three patients remain asymptomatic at 22- to 44-month follow-up. One patient (both hips) required total hip replacement due to widespread residual necrosis. Retrieved tissue engineered bone demonstrated a mature trabecular micro-architecture histologically and on μCT. Bone density and axial compression strength were comparable to trabecular bone. Conclusions Clinical follow-up shows this to be an effective new treatment for focal early stage avascular necrosis of the femoral head. Unique retrieval analysis of clinically translated tissue engineered bone has demonstrated regeneration of tissue that is both structurally and functionally analogous to normal trabecular bone. PMID:23540814

  10. Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN.

    PubMed

    Kumar, Santhosh V R; Kulkarni, Onkar P; Mulay, Shrikant R; Darisipudi, Murthy N; Romoli, Simone; Thomasova, Dana; Scherbaum, Christina R; Hohenstein, Bernd; Hugo, Christian; Müller, Susanna; Liapis, Helen; Anders, Hans-Joachim

    2015-10-01

    Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN.

  11. Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model.

    PubMed

    Bohr, Stefan; Patel, Suraj J; Sarin, Dhruv; Irimia, Daniel; Yarmush, Martin L; Berthiaume, Francois

    2013-01-01

    Deep partial thickness burns are subject to delayed necrosis of initially viable tissues surrounding the primary zone of thermally induced coagulation, which results in an expansion of the burn wound, both in area and depth, within 48 hours postburn. Neutrophil sequestration and activation leading to microvascular damage is thought to mediate this secondary tissue damage. Resolvins, a class of endogenous mediators derived from omega-3 polyunsaturated fatty acids, have been shown to regulate the resolution of inflammation. We hypothesized that exogenous resolvins could mitigate the deleterious impact of the inflammatory response in burn wounds. Using two different mouse burn injury models involving significant partial thickness injuries, we found that a systemically administered single dose of resolvin D2 (RvD2) as low as 25 pg/g bw given within an interval of up to 4 hours postburn effectively prevented thrombosis of the deep dermal vascular network and subsequent dermal necrosis. By preserving the microvascular network, RvD2 enhanced neutrophil access to the dermis, but prevented neutrophil-mediated damage through other anti-inflammatory actions, including inhibition of tumor necrosis factor-α, interleukin-1β, and neutrophil platelet-endothelial cell adhesion molecule-1. In a clinical context, RvD2 may be therapeutically useful by reducing the need for surgical debridement and the area requiring skin grafting. PMID:23110665

  12. Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model.

    PubMed

    Bohr, Stefan; Patel, Suraj J; Sarin, Dhruv; Irimia, Daniel; Yarmush, Martin L; Berthiaume, Francois

    2013-01-01

    Deep partial thickness burns are subject to delayed necrosis of initially viable tissues surrounding the primary zone of thermally induced coagulation, which results in an expansion of the burn wound, both in area and depth, within 48 hours postburn. Neutrophil sequestration and activation leading to microvascular damage is thought to mediate this secondary tissue damage. Resolvins, a class of endogenous mediators derived from omega-3 polyunsaturated fatty acids, have been shown to regulate the resolution of inflammation. We hypothesized that exogenous resolvins could mitigate the deleterious impact of the inflammatory response in burn wounds. Using two different mouse burn injury models involving significant partial thickness injuries, we found that a systemically administered single dose of resolvin D2 (RvD2) as low as 25 pg/g bw given within an interval of up to 4 hours postburn effectively prevented thrombosis of the deep dermal vascular network and subsequent dermal necrosis. By preserving the microvascular network, RvD2 enhanced neutrophil access to the dermis, but prevented neutrophil-mediated damage through other anti-inflammatory actions, including inhibition of tumor necrosis factor-α, interleukin-1β, and neutrophil platelet-endothelial cell adhesion molecule-1. In a clinical context, RvD2 may be therapeutically useful by reducing the need for surgical debridement and the area requiring skin grafting.

  13. Centrilobular zonal necrosis as a hallmark of a distinctive subtype of autoimmune hepatitis

    PubMed Central

    Abe, Hiroshi; Sugita, Tomonori; Seki, Nobuyoshi; Chuganji, Yoshimichi; Furumoto, Youhei; Sakata, Akihiko

    2016-01-01

    Background and aim Centrilobular zonal necrosis (CZN) is a known histological variant of autoimmune hepatitis (AIH). However, the significance of CZN is yet to be fully elucidated. This study aimed to determine whether CZN is a hallmark of a distinctive subtype of AIH. Methods Histological changes in the centrilobular zones of liver biopsies from 113 AIH patients were assessed by a single pathologist and classified into three categories: typical zonal necrosis defined as CZN (15 patients); other necroinflammatory change (NIC; 24 patients); and absence of necrosis (non-NIC; 74 patients). The clinicopathological features and immunogenetic background of CZN patients were then assessed. Results The clinicopathological features of AIH with CZN were distinct from other types of AIH, including a higher frequency of acute onset, lower frequency of antinuclear antibodies, lower antinuclear antibody titers, lower serum immunoglobulin G levels, lower grade interface hepatitis, less prominent lymphoplasmacytic infiltration, and lower AIH score. Increased and decreased frequencies of HLA-DR9 and HLA-DR4, respectively, were identified as immunogenetic features of AIH with CZN. Conversely, the clinicopathological characteristics of AIH with NIC were similar to those of non-NIC AIH, including the majority of the AIH patients. The therapeutic outcomes of AIH with CZN were excellent when precise diagnoses were made without delay. Conclusion The clinicopathological features and immunogenetic background of AIH with CZN differed from AIH without CZN. CZN may be a hallmark of a distinct subtype of AIH. PMID:26657454

  14. Neutrophil secondary necrosis is induced by LL-37 derived from cathelicidin.

    PubMed

    Zhang, Zhifang; Cherryholmes, Gregory; Shively, John E

    2008-09-01

    Neutrophils represent the most common granulocyte subtype present in blood. The short half-life of circulating neutrophils is regulated by spontaneous apoptosis, and tissue infiltrating neutrophils die by apoptosis and secondary necrosis. The mechanism of neutrophil apoptosis has been the subject of many studies; however, the mechanism of neutrophil secondary necrosis is less clear. Human cathelicidin cationic peptide 18, proteolytically processed to its active form, LL-37, is secreted by neutrophils and epithelial cells and shown to have effects in addition to bacterial lysis. We demonstrate here that LL-37 affects neutrophil lifespan by the pathway of secondary necrosis, rapidly converting annexin V-positive (AV(+)), propidium iodide-negative (PI(-); apoptotic) cells into PI(+) (necrotic) cells with the release of IL-8, IL-1R antagonist, ATP, and intact granules. The effects of LL-37 on apoptotic neutrophils are neither energy-dependent nor affected by pretreatment with G-CSF, GM-CSF, TNF-alpha, and LPS and are partially inhibited by human serum. Moreover, LL-37 decreases CXCR2 expression of AV(-)PI(-) (live) neutrophils, suggesting an effect on the neutrophil response to its chemotactic factors, including IL-8. Thus, the lifespan and inflammatory functions of neutrophils are directly affected by LL-37.

  15. Immunity to Rice Blast Disease by Suppression of Effector-Triggered Necrosis.

    PubMed

    Wang, Ruyi; Ning, Yuese; Shi, Xuetao; He, Feng; Zhang, Chongyang; Fan, Jiangbo; Jiang, Nan; Zhang, Yu; Zhang, Ting; Hu, Yajun; Bellizzi, Maria; Wang, Guo-Liang

    2016-09-26

    Hemibiotrophic pathogens are some of the most destructive plant pathogens, causing huge economic losses and threatening global food security. Infection with these organisms often involves an initial biotrophic infection phase, during which the pathogen spreads in host tissue asymptomatically, followed by a necrotrophic phase, during which host-cell death is induced. How hemibiotrophic pathogens trigger host necrosis and how plants inhibit the transition from the biotrophic stage to the necrotrophic stage in disease symptom expression are mainly unknown. The rice blast fungus Magnaporthe oryzae spreads in rice biotrophically early during infection, but this biotrophic stage is followed by a pronounced switch to cell death and lesion formation. Here, we show that the M. oryzae effector AvrPiz-t interacts with the bZIP-type transcription factor APIP5 in the cytoplasm and suppresses its transcriptional activity and protein accumulation at the necrotrophic stage. Silencing of APIP5 in transgenic rice leads to cell death, and the phenotype is enhanced by the expression of AvrPiz-t. Conversely, Piz-t interacts with and stabilizes APIP5 to prevent necrosis at the necrotrophic stage. At the same time, APIP5 is essential for Piz-t stability. These results demonstrate a novel mechanism for the suppression of effector-triggered necrosis at the necrotrophic stage by an NLR receptor in plants. PMID:27641772

  16. Bilateral scalp necrosis as a rare but devastating complication of giant cell arteritis.

    PubMed

    Akram, Q; Knight, S; Saravanan, R

    2015-01-01

    Giant cell arteritis (GCA) is a medium to large vessel vasculitis of unknown aetiology. Commonly, it affects the temporal arteries and is known as temporal arteritis. It has an association with polymyalgia rheumatica and can result in severe complications such as loss of vision and rarely scalp necrosis. There are approximately 100 cases of scalp necrosis in patients with GCA published in the literature to date. We report a case of a man who presented with a 4-week history of bilateral scalp necrosis associated with headache, jaw claudication, temporal artery tenderness, and raised inflammatory markers. He did not have any visual loss. A diagnosis of GCA was made and he was started on high-dose steroids immediately. The scalp lesions did improve and his symptoms resolved without any visual loss but, sadly he died due to severe sepsis. This case report is important as it describes a rare but severe complication of a common large vessel vasculitis seen by both primary care physicians and rheumatologists. Prompt recognition and early treatment by the physician are crucial to the patient to prevent visual loss or a fatal stroke. It also highlights complications associated with steroids which are the mainstay of treatment for this condition. PMID:25318611

  17. Upregulated RIP3 Expression Potentiates MLKL Phosphorylation-Mediated Programmed Necrosis in Toxic Epidermal Necrolysis.

    PubMed

    Kim, Sue Kyung; Kim, Woo-Jung; Yoon, Jung-Ho; Ji, Jae-Hoon; Morgan, Michael J; Cho, Hyeseong; Kim, You Chan; Kim, You-Sun

    2015-08-01

    Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction involving extensive keratinocyte death in the epidermis. Histologically, the skin from TEN patients exhibits separation at the dermo-epidermal junction and accompanying necrosis of epidermal keratinocytes. Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an essential part of the cellular machinery that executes "programmed", or "regulated", necrosis and has a key role in spontaneous cell death and inflammation in keratinocytes under certain conditions. Here we show that RIP3 expression is highly upregulated in skin sections from TEN patients and may therefore contribute to the pathological damage in TEN through activation of programmed necrotic cell death. The expression level of mixed lineage kinase domain-like protein (MLKL), a key downstream component of RIP3, was not significantly different in skin lesions of TEN. However, elevated MLKL phosphorylation was observed in the skin from TEN patients, indicating the presence of RIP3-dependent programmed necrosis. Importantly, in an in vitro model of TEN, dabrafenib, an inhibitor of RIP3, prevented RIP3-mediated MLKL phosphorylation and decreased cell death. Results from this study suggest that the high expression of RIP3 in keratinocytes from TEN patients potentiates MLKL phosphorylation/activation and necrotic cell death. Thus, RIP3 represents a potential target for treatment of TEN. PMID:25748555

  18. Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN

    PubMed Central

    Kumar, Santhosh V.R.; Kulkarni, Onkar P.; Mulay, Shrikant R.; Darisipudi, Murthy N.; Romoli, Simone; Thomasova, Dana; Scherbaum, Christina R.; Hohenstein, Bernd; Hugo, Christian; Müller, Susanna; Liapis, Helen

    2015-01-01

    Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti–glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN. PMID:25644111

  19. Effect of ribs in HIFU beam path on formation of coagulative necrosis in goat liver

    NASA Astrophysics Data System (ADS)

    Li, Faqi; Gong, Xiaobo; Hu, Kai; Li, Chongyan; Wang, Zhibiao

    2006-05-01

    The motives of the work are to explore the effect of ribs in HIFU beam path on HIFU ablation goat liver. A model-JC Focused Ultrasound Tumor Therapeutic System was used. A 0.75 MHz focused transducer with 150mm aperture and 120mm focal length was used in all experiment. Acoustical power can be adjusted. 30 goats were divided into control group (HIFU beam through rib cage, HIFU alone), experiment group 1(HIFU beam through rib cage, HIFU combined with microbubble) and experiment group 2(Ribs in HIFU beam path were surgically removed, HIFU alone). 20 targeted regions at 5cm away from skin surface were applied for creating necrosis with linear scanning of 15mm length using HIFU in 3 groups. All animals were sacrificed two days later and exposed organs were dissected. After obtaining the maximal section, the volumes of the necrotic regions were measured, then to calculate Energy Efficiency Factor (EEF). Researched results showed that Ribs in HIFU beam path affected the formation of coagulative necrosis and enhanced EEF in control group. HIFU combined with microbubble could enhance the formation of coagulative necrosis and decrease EEF.

  20. Postprimary Tuberculosis and Macrophage Necrosis: Is There a Big ConNECtion?

    PubMed Central

    2016-01-01

    ABSTRACT Adult or postprimary tuberculosis (TB) accounts for most TB cases. Its hallmark is pulmonary cavitation, which occurs as a result of necrosis in the lung in individuals with tuberculous pneumonia. Postprimary TB has previously been known to be associated with vascular thrombosis and delayed-type hypersensitivity, but their roles in pulmonary cavitation are unclear. A necrosis-associated extracellular cluster (NEC) refers to a cluster of drug-tolerant Mycobacterium tuberculosis attached to lysed host materials and is proposed to contribute to granulomatous TB. Here we suggest that NECs, perhaps due to big size, produce a distinct host response leading to postprimary TB. We propose that vascular thrombosis and pneumonia arise from NEC and that these processes are promoted by inflammatory cytokines produced from cell-mediated delayed-type hypersensitivity, such as interleukin-17 and gamma interferon, eventually triggering necrosis in the lung and causing cavitation. According to this view, targeting NEC represents a necessary strategy to control adult TB. PMID:26758178

  1. [Erosion and necrosis of the long process of the incus after otosclerosis operation].

    PubMed

    Schimanski, G

    1997-09-01

    The frequency and possible causes of erosion and necrosis of the long process of the incus induced by various types of prostheses following stapes surgery for otosclerosis are discussed. Between 1987 and 1995, 1144 stapes operations were performed including 117 revisions of stapes surgery performed by third parties and 27 revisions performed by the author. For the first time, necrosis of the long process of the incus caused by teflonplatinum piston is described on the basis of findings in five cases, in which the platinum loop had completely transmigrated the incudal process in a medial direction. By using pictures of the teflon-platinum piston and a gold piston taken by a scanning electron microscopy and a comparison between the use of a teflon-wire piston and a gold piston in two operations, an hypothesis is made that the winding grooves in the surface of the teflon shaft together with impaired middle ear mechanics were the main causes of a scar being contracted in the direction of the oval window niche with resulting necrosis of the incudal process. Requirements for an optimum stapes prosthesis are summarized as a result of the operative observations made. PMID:9417449

  2. Staphylococcus sciuri Exfoliative Toxin C (ExhC) is a Necrosis-Inducer for Mammalian Cells

    PubMed Central

    Li, Haihua; Wang, Yongqiang; Ding, Lin; Zheng, Shijun J.

    2011-01-01

    Staphylococcus sciuri (S. sciuri) is a rare pathogen in humans, but it can cause a wide array of human infections. Recently a S. sciuri isolate (HBXX06) was reported to cause fatal exudative epidermitis (EE) in piglets and thus considered as a potential zoonotic agent. To investigate the pathogenicity of this bacterium, we cloned exfoliative toxin C (ExhC), a major toxin of the S. sciuri isolate and performed functional analysis of the recombinant ExhC-his (rExhC) protein using in vitro cell cultures and newborn mice as models. We found that rExhC could induce necrosis in multiple cell lines and peritoneal macrophages as well as skin lesions in newborn mice, and that the rExhC-induced necrosis in cells or skin lesions in newborn mice could be completely abolished if amino acids 79-128 of rExhC were deleted or blocked with a monoclonal antibody (3E4), indicating aa 79-128 portion as an essential necrosis-inducing domain. This information contributes to further understandings of the mechanisms underlying S. sciuri infection. PMID:21829591

  3. The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis

    PubMed Central

    Rau, B; Steinbach, G; Gansauge, F; Mayer, J; Grunert, A; Beger, H

    1997-01-01

    Background—Infection of pancreatic necrosis has a major impact on clinical course, management, and outcome in acute pancreatitis. Currently, guided fine needle aspiration is the only means for an early and accurate diagnosis of infected necrosis. Procalcitonin (PCT), a 116 amino acid propeptide of calcitonin, and interleukin 8 (IL-8), a strong neutrophil activating cytokine, are markers of severe inflammation and sepsis. 
Aims—To analyse the clinical value of PCT and IL-8 as biochemical parameters for predicting infected necrosis in acute pancreatitis.
Patients and methods—Fifty patients with acute pancreatitis entered this prospective study and were stratified into three groups according to morphological and bacteriological findings: 18 patients with oedematous pancreatitis (group I), 14 patients with sterile necrosis (group II), and 18 patients who developed infected necrosis a median of 13.5 days after the onset of symptoms (group III). After admission serum samples were drawn daily for two weeks. Concentrations of PCT and IL-8 were measured by chemoluminescent immunoassays (upper reference range 0.5 ng/ml for PCT and 70 pg/ml for IL-8). The routine parameter C-reactive protein was determined by laser nephelometry (upper reference range 10 mg/l).
Results—Median concentrations of PCT and IL-8 were significantly higher in patients with infected necrosis than in those with sterile necrosis during the observation period, whereas there was no difference in C-reactive protein. In oedematous pancreatitis overall median concentrations of all three parameters were low. By receiver operating characteristics best cut off levels for predicting infected necrosis or persisting pancreatic sepsis were 1.8 ng/ml for PCT and 112 pg/ml for IL-8. If these cut off levels were reached on at least two days, sensitivity, specificity, and accuracy for the prediction of infected necrosis were 94%, 91%, and 92% for PCT and 72%, 75%, and 74% for IL-8, respectively. After

  4. Avascular Necrosis

    MedlinePlus

    ... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

  5. Full-length membrane-bound tumor necrosis factor-α acts through tumor necrosis factor receptor 2 to modify phenotype of sensory neurons.

    PubMed

    Wu, Zetang; Wang, Shiyong; Gruber, Sandy; Mata, Marina; Fink, David J

    2013-09-01

    Neuropathic pain resulting from spinal hemisection or selective spinal nerve ligation is characterized by an increase in membrane-bound tumor necrosis factor-alpha (mTNFα) in spinal microglia without detectable release of soluble TNFα (sTNFα). In tissue culture, we showed that a full-length transmembrane cleavage-resistant TNFα (CRTNFα) construct can act through cell-cell contact to activate neighboring microglia. We undertook the current study to test the hypothesis that mTNFα expressed in microglia might also affect the phenotype of primary sensory afferents, by determining the effect of CRTNFα expressed from COS-7 cells on gene expression in primary dorsal root ganglia (DRG) neurons. Co-culture of DRG neurons with CRTNFα-expressing COS-7 cells resulted in a significant increase in the expression of voltage-gated sodium channel isoforms NaV1.7 and NaV1.8, and voltage-gated calcium channel subunit CaV3.2 at both mRNA and protein levels, and enhanced CCL2 expression and release from the DRG neurons. Exposure to sTNFα produced an increase only in CCL2 expression and release. Treatment of the cells with an siRNA against tumor necrosis factor receptor 2 (TNFR2) significantly reduced CRTNFα-induced gene expression changes in DRG neurons, whereas administration of CCR2 inhibitor had no significant effect on CRTNFα-induced increase in gene expression and CCL2 release in DRG neurons. Taken together, the results of this study suggest that mTNFα expressed in spinal microglia can facilitate pain signaling by up-regulating the expression of cation channels and CCL2 in DRG neurons in a TNFR2-dependent manner. PMID:23711481

  6. Monitoring cell morphology during necrosis and apoptosis by quantitative phase imaging

    NASA Astrophysics Data System (ADS)

    Mugnano, Martina; Calabuig, Alejandro; Grilli, Simonetta; Miccio, Lisa; Ferraro, Pietro

    2015-05-01

    Cellular morphology changes and volume alterations play significant roles in many biological processes and they are mirrors of cell functions. In this paper, we propose the Digital Holographic microscope (DH) as a non-invasive imaging technique for a rapid and accurate extraction of morphological information related to cell death. In particular, we investigate the morphological variations that occur during necrosis and apoptosis. The study of necrosis is extremely important because it is often associated with unwarranted loss of cells in human pathologies such as ischemia, trauma, and some forms of neurodegeneration; therefore, a better elucidation in terms of cell morphological changes could pave the way for new treatments. Also, apoptosis is extremely important because it's involved in cancer, both in its formation and in medical treatments. Because the inability to initiate apoptosis enhances tumour formation, current cancer treatments target this pathway. Within this framework, we have developed a transmission off-axis DH apparatus integrated with a micro incubator for investigation of living cells in a temperature and CO2 controlled environment. We employ DH to analyse the necrosis cell death induced by laser light (wavelength 473 nm, light power 4 mW). We have chosen as cellular model NIH 3T3 mouse embryonic fibroblasts because their adhesive features such as morphological changes, and the time needed to adhere and spread have been well characterized in the literature. We have monitored cell volume changes and morphological alterations in real time in order to study the necrosis process accurately and quantitatively. Cell volume changes were evaluated from the measured phase changes of light transmitted through cells. Our digital holographic experiments showed that after exposure of cells to laser light for 90-120 min., they swell and then take on a balloon-like shape until the plasma membrane ruptures and finally the cell volume decreases. Furthermore, we

  7. Arabidopsis TTR1 causes LRR-dependent lethal systemic necrosis, rather than systemic acquired resistance, to Tobacco ringspot virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most Arabidopsis ecotypes display tolerance to the Tobacco ringspot virus (TRSV), but a subset of Arabidopsis ecotypes, including Estland (Est), develop lethal systemic necrosis (LSN), which differs from the localized hypersensitive responses (HRs) or systemic acquired resistance (SAR) characteristi...

  8. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.

    PubMed

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

  9. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

    PubMed Central

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called “second pathway of liver regeneration.” The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin. PMID:26136687

  10. A case of acute oesophageal necrosis (AEN) in a hypothermic patient. The grave prognosis of the black oesophagus.

    PubMed

    Salem, George A; Ahluwalia, Sumit; Guild, Ralph T

    2015-01-01

    Acute oesophageal necrosis, also known as black oesophagus, is a rare, and potentially lethal syndrome which is often diagnosed incidentally during upper endoscopy for evaluation of upper gastrointestinal bleed. It is characterised by diffuse circumferential black mucosal discolouration in the distal oesophagus secondary to necrosis that may extend proximally to involve variable length of the oesophagus. One theory of pathogenesis is that the relatively low perfusion state in the distal areas of the oesophagus makes it susceptible to mucosal injury. We present a case of acute oesophageal necrosis in a 62year-old lady with history of alcoholic cirrhosis who presented with haematemesis and severe hypothermia, and was eventually found to have acute oesophageal necrosis.

  11. Defective production of interleukin-1 and tumour necrosis factor-alpha by stimulated monocytes from patients with systemic lupus erythematosus.

    PubMed

    Mũzes, G; Vien, C V; González-Cabello, R; Fehér, J; Gergely, P

    1989-01-01

    Interleukin-1 and tumour necrosis factor-alpha activity by E. coli lipopolysaccharide-triggered monocytes was studied in patients with systemic lupus erythematosus in various stages of activity. Monocytes from both groups of SLE patients produced significantly less tumour necrosis factor-alpha activity than those of age and sex matched healthy controls. However, interleukin-1 activity was only significantly reduced in patients with active stage of the disease. These findings indicate further immunoregulatory disturbances in monocyte function concerning SLE. PMID:2636360

  12. Complete Genomic Characterization of Plum bark necrosis stem pitting-associated virus Infecting Sweet Cherry in China.

    PubMed

    Wang, Jiawei; Zhai, Ying; Liu, Weizhen; Zhu, Dongzi; Pappu, Hanu R; Liu, Qingzhong

    2016-01-01

    Plum bark necrosis stem pitting-associated virus (PBNSPaV) causes the plum bark necrosis stem pitting-associated disease. We obtained the complete genome of a PBNSPaV isolate (PBNSPaV-TA) using small RNA deep sequencing followed by overlapping RT-PCR. To our knowledge, this is the first report of a completed genome of PBNSPaV identified from cherry trees. PMID:27198034

  13. RIP3 induces ischemic neuronal DNA degradation and programmed necrosis in rat via AIF

    PubMed Central

    Xu, Yang; Wang, Jingye; Song, Xinghui; Qu, Lindi; Wei, Ruili; He, Fangping; Wang, Kai; Luo, Benyan

    2016-01-01

    We have reported that nuclear translocation of Receptor-interacting protein 3 (RIP3) involves in neuronal programmed necrosis after 20-min global cerebral ischemia/reperfusion (I/R) injury. Herein, the underlying mechanisms and the nuclear role of RIP3 were investigated further. The necroptosis inhibitor necrostatin-1 (Nec-1), the autophagy inhibitor 3-methyladenine (3-MA), and the caspase-3 inhibitor acetyl-L-aspartyl-L-methionyl-L-glutaminyl-L-aspart-1-al (Ac-DMQD-CHO) were administered intracerebroventricularly 1 h before ischemia. Protein expression, location and interaction was determined by western blot, immunofluorescence or immunoprecipitation. Most CA1 neuronal death induced by 20-min global cerebral I/R injury was TUNEL-positive. Neuronal death and rat mortality rates were greatly inhibited by Nec-1 and 3-MA pre-treatment, but not by Ac-DMQD-CHO. And no activation of caspase-3 was detected after I/R injury. Caspase-8 was expressed richly in GFAP-positive astrocytes and Iba-1-positive microglia, but was not detected in Neun-positive neurons. The nuclear translocation and co-localization of RIP3 and AIF, and their interaction were detected after I/R injury. These processes were inhibited by Nec-1 and 3-MA pre-treatment, but not by Ac-DMQD-CHO. The formation of an RIP3-AIF complex and its nuclear translocation are critical to ischemic neuronal DNA degradation and programmed necrosis. Neurons are more likely to enter the programmed necrosis signal pathway for the loss of caspase-8 suppression. PMID:27377128

  14. Glycans coated silver nanoparticles induces autophagy and necrosis in HeLa cells

    NASA Astrophysics Data System (ADS)

    Panzarini, Elisa; Mariano, Stefania; Dini, Luciana

    2015-06-01

    This study reports the induction of autophagy by two concentrations (2×103 or 2×104 NPs/cell) of 30 nm sized β-D-Glucose- and β-D-Glucose/Sucrose-coated silver NanoParticles (AgNPs-G and AgNPs-GS respectively) in HeLa cells treated for 6, 12, 24 and 48 hrs. Cell viability was assessed by Neutral Red (NR) test and morphological evaluation. In addition ROS generation (NBT test) and induction of apoptosis/necrosis (Annexin V/Propidium Iodide-Annexin V/PI staining) and autophagy (Monodansylcadaverine-MDC staining) were evaluated. Cytotoxicity, ROS generation and morphology changes depend on NPs type and amount, and incubation time. As a general result, AgNPs-G are more toxic than AgNPs-GS. Moreover, the lowest AgNPs-GS concentration is ineffective on cell viability and ROS generation. Only 10% and 25% of viable HeLa cells were found at the end of incubation time in the presence of higher amount of AgNPs - G and AgNPs-GS respectively and in parallel ROS generation is induced. To elucidate the type of cell death, Annexin V/PI and MDC staining was performed. Interestingly, irrespective of coating type and NPs amount the percentage of apoptotic cells (Annexin V+/PI-) is similar to viable HeLa cells. At contrary, we observed a NPs amount dependent autophagy and necrosis induction. In fact, the lower amount of NPs induces autophagy (MDC+/PI- cells) whereas the higher one induces necrosis (Annexin V+/PI+ cells). Our findings suggest that AgNPs-induced cytotoxicity depends on AgNPs amount and type and provide preliminary evidence of induction of autophagy in HeLa cells cultured in the presence of AgNPs.

  15. Bile Acid-Induced Necrosis in Primary Human Hepatocytes and in Patients with Obstructive Cholestasis

    PubMed Central

    Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.; Clarke, Joanna I.; Gholami, Parviz; Li, Feng; Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson; Fan, Fang; Jenkins, Rosalind E.; Park, B. Kevin; Hagenbuch, Bruno; Olyaee, Mojtaba; Jaeschke, Hartmut

    2015-01-01

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. PMID:25636263

  16. Thermally induced apoptosis, necrosis, and heat shock protein expression in 3D culture.

    PubMed

    Song, Alfred S; Najjar, Amer M; Diller, Kenneth R

    2014-07-01

    This study was conducted to compare the heat shock responses of cells grown in 2D and 3D culture environments as indicated by the level of heat shock protein 70 expression and the incidence of apoptosis and necrosis of prostate cancer cell lines in response to graded hyperthermia. PC3 cells were stably transduced with a dual reporter system composed of two tandem expression cassettes-a conditional heat shock protein promoter driving the expression of green fluorescent protein (HSPp-GFP) and a cytomegalovirus (CMV) promoter controlling the constitutive expression of a "beacon" red fluorescent protein (CMVp-RFP). Two-dimensional and three-dimensional cultures of PC3 prostate cancer cells were grown in 96-well plates for evaluation of their time-dependent response to supraphysiological temperature. To induce controlled hyperthermia, culture plates were placed on a flat copper surface of a circulating water manifold that maintained the specimens within ±0.1°C of a target temperature. Hyperthermia protocols included various combinations of temperature, ranging from 37°C to 57°C, and exposure times of up to 2 h. The majority of protocols were focused on temperature and time permutations, where the response gradient was greatest. Post-treatment analysis by flow cytometry analysis was used to measure the incidences of apoptosis (annexin V-FITC stain), necrosis (propidium iodide (PI) stain), and HSP70 transcription (GFP expression). Cells grown in 3D compared with 2D culture showed reduced incidence of apoptosis and necrosis and a higher level of HSP70 expression in response to heat shock at the temperatures tested. Cells responded differently to hyperthermia when grown in 2D and 3D cultures. Three-dimensional culture appears to enhance survival plausibly by activating protective processes related to enhanced-HSP70 expression. These differences highlight the importance of selecting physiologically relevant 3D models in assessing cellular responses to hyperthermia in

  17. Profiles of metabolites and gene expression in rats with chemically induced hepatic necrosis.

    PubMed

    Heijne, Wilbert H M; Lamers, Robert-Jan A N; van Bladeren, Peter J; Groten, John P; van Nesselrooij, Joop H J; van Ommen, Ben

    2005-01-01

    This study investigated whether integrated analysis of transcriptomics and metabolomics data increased the sensitivity of detection and provided new insight in the mechanisms of hepatotoxicity. Metabolite levels in plasma or urine were analyzed in relation to changes in hepatic gene expression in rats that received bromobenzene to induce acute hepatic centrilobular necrosis. Bromobenzene-induced lesions were only observed after treatment with the highest of 3 dose levels. Multivariate statistical analysis showed that metabolite profiles of blood plasma were largely different from controls when the rats were treated with bromobenzene, also at doses that did not elicit histopathological changes. Changes in levels of genes and metabolites were related to the degree of necrosis, providing putative novel markers of hepatotoxicity. Levels of endogenous metabolites like alanine, lactate, tyrosine and dimethylglycine differed in plasma from treated and control rats. The metabolite profiles of urine were found to be reflective of the exposure levels. This integrated analysis of hepatic transcriptomics and plasma metabolomics was able to more sensitively detect changes related to hepatotoxicity and discover novel markers. The relation between gene expression and metabolite levels was explored and additional insight in the role of various biological pathways in bromobenzene-induced hepatic necrosis was obtained, including the involvement of apoptosis and changes in glycolysis and amino acid metabolism. The complete Table 2 is available as a supplemental file online at http://taylorandfrancis.metapress.com/openurlasp?genre=journal&issn=0192-6233. To access the file, click on the issue link for 33(4), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath.org. PMID:16036859

  18. Assessment of MRI Parameters as Imaging Biomarkers for Radiation Necrosis in the Rat Brain

    SciTech Connect

    Wang Silun; Tryggestad, Erik; Zhou Tingting; Armour, Michael; Wen Zhibo; Fu Dexue; Ford, Eric; Zijl, Peter C.M. van; Zhou Jinyuan

    2012-07-01

    Purpose: Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T{sub 1}, T{sub 2}, apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Methods and Materials: Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 Multiplication-Sign 10 mm{sup 2}) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at {approx}25 weeks' postradiation. The MRI signals of necrotic cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. Results: ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T{sub 1}, T{sub 2}, MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T{sub 1}, T{sub 2}, MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. Conclusion: ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores.

  19. Hyperbaric oxygen reduces edema and necrosis of skeletal muscle in compartment syndromes associated with hemorrhagic hypotension

    SciTech Connect

    Skyhar, M.J.; Hargens, A.R.; Strauss, M.B.; Gershuni, D.H.; Hart, G.B.; Akeson, W.H.

    1986-10-01

    This study examined the effect of exposures to hyperbaric oxygen on the development of the edema and necrosis of muscle that are associated with compartment syndromes that are complicated by hemorrhagic hypotension. A compartment syndrome (twenty millimeters of mercury for six hours) was induced by infusion of autologous plasma in the anterolateral compartment of the left hind limb of seven anesthetized dogs while the mean arterial blood pressure was maintained at sixty-five millimeters of mercury after 30 per cent loss of blood volume. These dogs were treated with hyperbaric oxygen (two atmospheres of pure oxygen) and were compared with six dogs that had an identical compartment syndrome and hypotensive condition but were not exposed to hyperbaric oxygen. Forty-eight hours later, edema was quantified by measuring the weights of the muscles (the pressurized muscle compared with the contralateral muscle), and necrosis of muscle was evaluated by measuring the uptake of technetium-99m stannous pyrophosphate. The ratio for edema was significantly (p = 0.01) greater in dogs that had not been exposed to hyperbaric oxygen (1.15 +/- 0.01) than in the dogs that had been treated with hyperbaric oxygen (1.01 +/- 0.03), and the ratio for necrosis of muscle was also significantly (p = 0.04) greater in dogs that had not had hyperbaric oxygen (1.96 +/- 0.41) than in those that had been treated with hyperbaric oxygen (1.05 +/- 0.11). Comparisons were also made with the muscles of four normal control dogs and separately with the muscles of six normotensive dogs that had an identical compartment syndrome and normal blood pressure and were not treated with hyperbaric oxygen.

  20. Susceptibility of Australian Redfin Perch Perca fluviatilis Experimentally Challenged with Epizootic Hematopoietic Necrosis Virus (EHNV).

    PubMed

    Becker, Joy A; Tweedie, Alison; Gilligan, Dean; Asmus, Martin; Whittington, Richard J

    2016-06-01

    The ranavirus epizootic hematopoietic necrosis virus (EHNV) is endemic to Australia and is listed by the Office International des Epizooties. Clinical outbreaks have only been observed in wild populations of Redfin Perch Perca fluviatilis (also known as Eurasian Perch) and farmed populations of Rainbow Trout Oncorhynchus mykiss. The initial outbreaks of EHNV describe all age-classes of Redfin Perch as being susceptible and can lead to epidemic fish kills. Subsequently, experimental challenge studies using either cohabitation with the virus or injection exposures resulted in mixed susceptibilities across various age-groupings of Redfin Perch. We used an experimental bath challenge model to investigate the susceptibility of Redfin Perch collected from areas with and without a history of EHNV outbreaks. The median survival time for fish from Blowering Dam in New South Wales, a zone with a history of EHNV outbreaks, was 35 d, compared with fish from other areas, which had a median survival between 12 and 28 d postexposure. Redfin Perch from Blowering Dam demonstrated an increased mortality associated with epizootic hematopoietic necrosis up to approximately day 14 after exposure, and then there was a significantly reduced risk of mortality until the end of the trial compared with all other fish. Redfin Perch from Blowering Dam had markedly decreased susceptibility to EHNV, and less than 40% became infected following a bath challenge. In contrast, Redfin Perch from neighboring (e.g., Bethungra Dam and Tarcutta Creek) and distant water bodies (e.g., in Western Australia) with no previous history of EHNVdisplayed moderate to high susceptibility when given a bath challenge. Potential factors for the observed changes in the host-pathogen relationship include intense positive selection pressure for resistant fish following epizootic hematopoietic necrosis outbreaks and subsequent attenuation of the virulence of the virus in resistant fish. Received August 22, 2015; accepted

  1. THE INFLUENCE OF THYROID PRODUCTS ON THE PRODUCTION OF MYOCARDIAL NECROSIS

    PubMed Central

    Goodpasture, Ernest W.

    1921-01-01

    An experimental study upon the demonstrable effects of large doses of dried thyroid gland and thyroxin upon the myocardium of rabbits has been made. Animals under such treatment show characteristic clinical symptoms with definite, although relatively slight, myocardial lesions. Similarly treated animals which have, in addition, been subjected to chloroform anesthesia show more striking, widespread myocardial necrosis. These experiments indicate very distinctly that chloroform as an anesthetic in cases of hyperthyroidism is apt to be exceptionally detrimental to the myocardium, and should be avoided. PMID:19868566

  2. Multiple roles of tumor necrosis factor-alpha in fracture healing.

    PubMed

    Karnes, Jonathan M; Daffner, Scott D; Watkins, Colleen M

    2015-09-01

    This review presents a summary of basic science evidence examining the influence of tumor necrosis factor-alpha (TNF-α) on secondary fracture healing. Multiple studies suggest that TNF-α, in combination with the host reservoir of peri-fracture mesenchymal stem cells, is a main determinant in the success of bone healing. Disease states associated with poor bone healing commonly have inappropriate TNF-α responses, which likely contributes to the higher incidence of delayed and nonunions in these patient populations. Appreciation of TNF-α in fracture healing may lead to new therapies to augment recovery and reduce the incidence of complications.

  3. [IDENTIFICATION OF THE INFECTIOUS PANCREATIC NECROSIS VIRUS (IPNV) USING THE ENZYME IMMUNOASSAY].

    PubMed

    Zavyalova, E A; Gulyukin, M I; Carpova, M A; Bogdanova, P D; Droshnev, A E

    2016-01-01

    The infectious pancreatic necrosis (IPN) caused by a non-enveloped virus of the Birnaviridae family is one of the most important loss factors in the salmonid aquaculture. Virus isolation in the sensitive cell cultures has been approved in the Russian Federation as the diagnostic method for determination of IPNV antigen. This work gives the results of the development of the diagnostic test to reveal IPNV using the antigen-bound ELISA (sandwich ELISA). The developed test supplements a new diagnostic method and verifies some disputable results obtained with classical methods. PMID:27145601

  4. Q Fever Risk in Patients Treated with Chronic Antitumor Necrosis Factor-Alpha Therapy

    PubMed Central

    Astrahan, Anna; Odeh, Majed; Elias, Nizar; Rosner, Itzhak; Rimar, Doron; Kaly, Lisa; Rozenbaum, Michael; Boulman, Nina; Slobodin, Gleb

    2016-01-01

    Q fever is a zoonotic bacterial disease caused by Coxiella burnetii. Tumor necrosis factor-alpha (TNF-α) plays a pivotal role in the defense against infection with this Gram-negative coccobacillus. Theoretically, patients who are treated with anti-TNF-α medications are at risk for developing chronic Q fever. We present two patients who developed Q fever while being treated with anti-TNF-α agents and discuss the significance of timely diagnosis of C. burnetii infection in these patients. PMID:27656302

  5. Effects of interferon-gamma and tumor necrosis factor-alpha on macrophage enzyme levels

    NASA Technical Reports Server (NTRS)

    Pierangeli, Silvia S.; Sonnenfeld, Gerald

    1989-01-01

    Murine peritoneal macrophages were treated with interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF). Measurements of changes in acid phosphatase and beta-glucuronidase levels were made as an indication of activation by cytokine treatment. IFN-gamma or TNF-gamma treatment resulted in a significant increase in the activities of both enzymes measured in the cell lysates. This increase was observable after 6 h of incubation, but reached its maximum level after 24 h of incubation. The effect of the treatment of the cell with both cytokines together was additive. No synergistic effect of addition of both cytokines on the enzyme levels was observed.

  6. Levator Ani Necrosis: An Exceptional Complication Occurring after "High Intensity Focused Ultrasound" of the Prostate.

    PubMed

    Badawy, Danny; El Rassy, Elie; Aoun, Fouad; Van Velthoven, Roland

    2016-01-01

    High intensity focused ultrasound (HIFU) is a minimally invasive treatment option that might be considered in the management of localized prostate cancer. It is a well-tolerated treatment with few minor urologic complications and no major toxicities. In this paper, we report to our knowledge the first case of levator ani necrosis in a patient treated with HIFU, manifesting as sturdy perineal pain, which took years of NSAID intake and serial MRIs to demonstrate partial improvement. Therefore, we regard HIFU as a serious potential treatment option that still requires longer follow-up data before its approval in the personalized treatment panel of prostate cancer.

  7. Renal Papillary Necrosis Caused by Protein C Deficiency Leading to Recurrent Hydronephrosis

    PubMed Central

    Olorunnisomo, Vincent; Fowle, Evan James; Modica, Ippolito; Meisels, Ira; Gupta, Mantu

    2016-01-01

    Abstract A patient with history of a solitary functioning kidney and protein C deficiency (PCD) presented with recurrent severe hydronephrosis causing acute kidney injury upon chronic kidney disease. Work-up with endoscopic evaluation revealed renal papillary necrosis (RPN) and sloughed renal papillae to be the true cause of the recurrent obstruction. Pathologic evaluation of the sloughed tissue confirmed the diagnosis of RPN. This is the first case reported in the literature illustrating the unique presentation of RPN in the setting of PCD. PMID:27579411

  8. Sequential tests for infectious hematopoietic necrosis virus in individuals and populations of sockeye salmon

    USGS Publications Warehouse

    Mulcahy, D.; Pascho, R.J.

    1986-01-01

    The incidence and titer distribution of infectious hematopoietic necrosis virus in cavity fluid from spent female sockeye salmon (Oncorhynchus nerka) varied little when fish from a naturally spawning population were sampled three times on alternate days. However, when prespawning female sockeye salmon from a second population were individually tagged, penned, and sampled daily, the incidence and proportion of fish with high virus titer rose over a 6-d period. In 10 instances, consecutive cavity fluid samples from the same fish reverted from virus-positive to virus-negative. We suggest that spent fish should be sampled when accurate and quantitative data on the incidence and level of the virus are required.

  9. An aptasensor for electrochemical detection of tumor necrosis factor in human blood.

    PubMed

    Liu, Ying; Zhou, Qing; Revzin, Alexander

    2013-08-01

    Electrochemical aptasensors can detect disease markers such as cytokines to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive. Herein, we describe the development of an aptamer-based electrochemical sensor for detection and analysis of tumor necrosis factor-alpha (TNF-α) - a key inflammatory cytokine - in whole human blood. When testing spiked blood, a TNF-α detection limit of 58 pM (10 ng mL(-1)) and a linear range of 6 nM (100 ng mL(-1)) could be achieved. Furthermore, detection of TNF-α in mitogen stimulated whole blood was demonstrated.

  10. Pancreaticoportal Fistula and Disseminated Fat Necrosis After Revision of a Transjugular Intrahepatic Portosystemic Shunt

    SciTech Connect

    Klein, Seth J. Saad, Nael; Korenblat, Kevin; Darcy, Michael D.

    2013-04-15

    A 59-year old man with alcohol related cirrhosis and portal hypertension was referred for transjugular intrahepatic portosystemic shunt (TIPS) to treat his refractory ascites. Ten years later, two sequential TIPS revisions were performed for shunt stenosis and recurrent ascites. After these revisions, he returned with increased serum pancreatic enzyme levels and disseminated superficial fat necrosis; an iatrogenic pancreaticoportal vein fistula caused by disruption of the pancreatic duct was suspected. The bare area of the TIPS was subsequently lined with a covered stent-graft, and serum enzyme levels returned to baseline. In the interval follow-up period, the patient has clinically improved.

  11. Control of infectious Hematopoietic Necrosis virus disease by elevating the water temperature

    USGS Publications Warehouse

    Amend, Donald F.

    1970-01-01

    Studies were performed to determine if increasing water temperatures could control infectious hematopoietic necrosis virus (IHN) disease in sockeye salmon (Oncorhynchus nerka). Mortalities could be prevented if the water temperature was raised to at least 18 C within the first 24 hr after infection of the fish and if the fish were maintained at this temperature for 4–6 days. The disease did not recur after the elevated temperature treatment, but the fish would still contract the disease if they were reinfected. Reasons for the protecting action are discussed.

  12. Q Fever Risk in Patients Treated with Chronic Antitumor Necrosis Factor-Alpha Therapy

    PubMed Central

    Astrahan, Anna; Odeh, Majed; Elias, Nizar; Rosner, Itzhak; Rimar, Doron; Kaly, Lisa; Rozenbaum, Michael; Boulman, Nina; Slobodin, Gleb

    2016-01-01

    Q fever is a zoonotic bacterial disease caused by Coxiella burnetii. Tumor necrosis factor-alpha (TNF-α) plays a pivotal role in the defense against infection with this Gram-negative coccobacillus. Theoretically, patients who are treated with anti-TNF-α medications are at risk for developing chronic Q fever. We present two patients who developed Q fever while being treated with anti-TNF-α agents and discuss the significance of timely diagnosis of C. burnetii infection in these patients.

  13. Levator Ani Necrosis: An Exceptional Complication Occurring after "High Intensity Focused Ultrasound" of the Prostate.

    PubMed

    Badawy, Danny; El Rassy, Elie; Aoun, Fouad; Van Velthoven, Roland

    2016-01-01

    High intensity focused ultrasound (HIFU) is a minimally invasive treatment option that might be considered in the management of localized prostate cancer. It is a well-tolerated treatment with few minor urologic complications and no major toxicities. In this paper, we report to our knowledge the first case of levator ani necrosis in a patient treated with HIFU, manifesting as sturdy perineal pain, which took years of NSAID intake and serial MRIs to demonstrate partial improvement. Therefore, we regard HIFU as a serious potential treatment option that still requires longer follow-up data before its approval in the personalized treatment panel of prostate cancer. PMID:27672474

  14. Programmed necrosis: backup to and competitor with apoptosis in the immune system.

    PubMed

    Han, Jiahuai; Zhong, Chuan-Qi; Zhang, Duan-Wu

    2011-11-16

    Programmed cell death is essential for the development and maintenance of the immune system and its responses to exogenous and endogenous stimuli. Studies have demonstrated that in addition to caspase-dependent apoptosis, necrosis dependent on the kinases RIP1 and RIP3 (also called necroptosis) is a major programmed cell-death pathway in development and immunity. These two programmed cell-death pathways may suppress each other, and necroptosis also serves as an alternative when caspase-dependent apoptosis is inhibited or absent. Here we summarize recent advancements that have identified the molecular mechanisms that underlie necroptosis and explore the mechanisms that regulate the interplay between apoptosis and necroptosis.

  15. Effect of repetitive ozone treatment on bean plants—stress ethylene production and leaf necrosis

    NASA Astrophysics Data System (ADS)

    Stan, Hans-Jürgen; Schicker, Sieglinde

    Bean plants were repetitively treated with varying ozone (O 3) concentrations and exposure times on successive days. Our studies clearly demonstrate that a series of successive short episodes of ozone exposure is more damaging to the plants than continuous exposure of the same O 3 concentration for the same total exposure time. In contrast to single ozone exposure experiments repetitive ozone treatment causes stress ethylene production and the beginning of leaf necrosis at the same time. The "no effect levels" estimated for O 3 with single exposure experiments can not be applied to repetitive ozone exposure episodes because the plants are more sensitive under these conditions.

  16. Genotyping of Korean isolates of infectious hematopoietic necrosis virus (IHNV) based on the glycoprotein gene

    USGS Publications Warehouse

    Kim, W.-S.; Oh, M.-J.; Nishizawa, T.; Park, J.-W.; Kurath, G.; Yoshimizu, M.

    2007-01-01

    Glycoprotein (G) gene nucleotide sequences of four Korean isolates of infectious hematopoietic necrosis virus (IHNV) were analyzed to evaluate their genetic relatedness to worldwide isolates. All Korean isolates were closely related to Japanese isolates of genogroup JRt rather than to those of North American and European genogroups. It is believed that Korean IHNV has been most likely introduced from Japan to Korea by the movement of contaminated fish eggs. Among the Korean isolates, phylogenetically distinct virus types were obtained from sites north and south of a large mountain range, suggesting the possibility of more than one introduction of virus from Japan. ?? 2007 Springer-Verlag.

  17. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    NASA Astrophysics Data System (ADS)

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  18. FDG PET/CT Findings in Abdominal Fat Necrosis After Treatment for Lymphoma.

    PubMed

    Dubreuil, Julien; Moreau, Aurélie; Sarkozy, Clémentine; Traverse-Glehen, Alexandra; Skanjeti, Andrea; Salles, Gilles; Giammarile, Francesco

    2016-05-01

    FDG PET/CT is now validated in non-Hodgkin lymphoma for response assessment in interim and posttreatment lymphoma. We report the case of a 62-year-old man followed by FDG PET/CT for a diffuse large B-cell lymphoma, with initial stage III. The interim FDG PET/CT examination concluded in complete metabolic and morphological response of subdiaphragmatic lymphadenopathy but a persistent abnormal subdiaphragmatic uptake (SUVmax at 9 and Deauville 5-point scale at 5). Therefore, an abdominal biopsy of the corresponding nodules was conducted with a final diagnosis of diffuse fat necrosis. PMID:26825213

  19. Progressive midfacial bone erosion and necrosis: case report and differential diagnosis.

    PubMed

    Bianchi, Francesca Antonella; Gerbino, Giovanni; Tosco, Paolo; Tanteri, Giulia; Gatti, Gaia; Ramieri, Guglielmo

    2014-12-01

    A 31-year-old woman presented with a large oro-nasal communication (ONC), loss of vomer and significant nasal cartilage and nose deformity. Physical examination of the patient revealed a typical midline destructive lesion (MDL) with nasal septum and hard/soft palate perforation with a friable granular surface and a large amount of necrotic tissues. Medical history was unremarkable and the patient denied previous local trauma, including surgical procedures or drug assumption. Pathological examination revealed the presence of necrosis and chronic inflammation. MDLs have numerous etiologies. Signs and symptoms of MDLs can be similar and an accurate diagnosis may be elusive. We hereby present detailed clinicopathological findings. PMID:25048049

  20. Shock wave therapy as a treatment of nonunions, avascular necrosis, and delayed healing of stress fractures.

    PubMed

    Furia, John P; Rompe, Jan D; Cacchio, Angelo; Maffulli, Nicola

    2010-12-01

    Shock wave therapy (SWT) stimulates angiogenesis and osteogenesis. SWT is commonly used to treat soft tissue musculoskeletal conditions such as fasciopathies and tendinopathies. Recent basic science and clinical data suggest that SWT can also be used to treat disorders of bone. Nonunions, avascular necrosis, and delayed healing of stress fractures have all been successfully treated with SWT. Success rates with SWT are equal to those with standard surgical treatment, but SWT has the advantage of decreased morbidity. The procedure is safe, well tolerated, yields few complications, and, typically, can be performed on an outpatient basis. SWT is a viable noninvasive alternative to stimulate healing of bone.

  1. New advances in the mesenchymal stem cells therapy against skin flaps necrosis.

    PubMed

    Zhang, Fu-Gui; Tang, Xiu-Fa

    2014-09-26

    Mesenchymal stem cells (MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various cells, such as osteoblasts, adipocytes, chondrocytes, vascular endothelial progenitor cells, and other cell types. MSCs are being widely studied as potential cell therapy agents due to their angiogenic properties, which have been well established by in vitro and in vivo researches. Within this context, MSCs therapy appears to hold substantial promise, particularly in the treatment of conditions involving skin grafts, pedicle flaps, as well as free flaps described in literatures. The purpose of this review is to report the new advances and mechanisms underlying MSCs therapy against skin flaps necrosis.

  2. Neutralizing monoclonal antibodies recognize antigenic variants among isolates of infectious hematopoietic necrosis virus

    USGS Publications Warehouse

    Winton, J.R.; Arakawa, C.N.; Lannan, C.N.; Fryer, J.L.

    1988-01-01

    eutralizing monoclonal antibodies were developed against strains of infectious hematopoietic necrosis virus (IHNV) from steelhead trout Salmo gairdneri in the Deschutes River of Oregon, chinook salmon Oncorhynchus tshawytscha in the Sacramento River of California, and rainbow trout Salmo gairdneri reared in the Hagerman Valley of Idaho, USA. These antibodies were tested for neutralization of 12 IHNV isolates obtained from salmonids in Japan, Alaska, Washington, Oregon, California, and Idaho. The antibodies recognized antigenic variants among the isolates and could be used to separate the viruses into 4 groups. The members of each group tended to be related by geographic area rather than by source host species, virulence, or date of isolation.

  3. Effects of Tumor Necrosis Factor Alpha on Sin Nombre Virus Infection In Vitro

    PubMed Central

    Khaiboullina, Svetlana F.; Netski, Dale M.; Krumpe, Peter; St. Jeor, Stephen C.

    2000-01-01

    Previous data indicate that immune mechanisms may be involved in developing capillary leakage during Sin Nombre virus (SNV) infection. Therefore, we investigated production of tumor necrosis factor alpha (TNF-α) by human alveolar macrophages and human umbilical vein endothelial cells (HUVEC) after infection with SNV. In addition, we examined the effect of TNF-α on HUVEC monolayer leakage. Our results reveal that although TNF-α decreases accumulation of viral nucleoproteins, TNF-α levels do not change in SNV-infected cells. In addition, supernatants from SNV-infected human alveolar macrophages did not cause a significant increase in endothelial monolayer permeability. PMID:11090198

  4. Tumour necrosis factor (TNF alpha) in leishmaniasis. I. TNF alpha mediates host protection against cutaneous leishmaniasis.

    PubMed Central

    Liew, F Y; Parkinson, C; Millott, S; Severn, A; Carrier, M

    1990-01-01

    Genetically resistant CBA mice developed significantly larger lesions to Leishmania major infection when they were injected with rabbit anti-tumour necrosis factor (TNF)-specific antibodies compared to control mice injected with normal rabbit immunoglobulin. BALB/c mice recovered from a previous infection following prophylactic sublethal irradiation also developed exacerbated lesions when treated with the anti-TNF antibody. Injection of TNF into the lesion of infected CBA mice significantly reduced the lesion development. Furthermore, TNF activates macrophages to kill Leishmania in vitro. These data demonstrate that TNF plays an important role in mediating host-protection against cutaneous leishmaniasis. PMID:2335376

  5. Aseptic necrosis of the femoral head after pregnancy: a case report

    PubMed Central

    Nassar, Kawtar; Rachidi, Wafae; Janani, Saadia; Mkinsi, Ouafa

    2016-01-01

    A documented case of beginning aseptic necrosis of the femoral head associated with pregnancy together with a review of the literature about this rare complication of pregnancy is presented. The known risk factors of osteonecrosis are; steroid use, alcoholism, organ transplantation, especially after kidney transplant or bone marrow transplantation bone, systemic lupus erythematosus, dyslipidemia especially hypertriglyceridemia, dysbaric decompression sickness, drepanocytosis and Gaucher's disease. Among the less established factors, we mention procoagulations abnormalities, HIV infection, chemotherapy. We report a case of osteonecrosis of femoral head after pregnancy. PMID:27795792

  6. Neutrophil Recruitment by Tumor Necrosis Factor from Mast Cells in Immune Complex Peritonitis

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Ramos, Bernard F.; Jakschik, Barbara A.

    1992-12-01

    During generalized immune complex-induced inflammation of the peritoneal cavity, two peaks of tumor necrosis factor (TNF) were observed in the peritoneal exudate of normal mice. In mast cell-deficient mice, the first peak was undetected, and the second peak of TNF and neutrophil influx were significantly reduced. Antibody to TNF significantly inhibited neutrophil infiltration in normal but not in mast cell-deficient mice. Mast cell repletion of the latter normalized TNF, neutrophil mobilization, and the effect of the antibody to TNF. Thus, in vivo, mast cells produce the TNF that augments neutrophil emigration.

  7. Cell Death and Inflammatory Bowel Diseases: Apoptosis, Necrosis, and Autophagy in the Intestinal Epithelium

    PubMed Central

    2014-01-01

    Cell death mechanisms have been associated with the development of inflammatory bowel diseases in humans and mice. Recent studies suggested that a complex crosstalk between autophagy/apoptosis, microbe sensing, and enhanced endoplasmic reticulum stress in the epithelium could play a critical role in these diseases. In addition, necroptosis, a relatively novel programmed necrosis-like pathway associated with TNF receptor activation, seems to be also present in the pathogenesis of Crohn's disease and in specific animal models for intestinal inflammation. This review attempts to cover new data related to cell death mechanisms and inflammatory bowel diseases. PMID:25126549

  8. Increased tumor necrosis factor alpha mRNA after cellular exposure to ionizing radiation.

    PubMed Central

    Hallahan, D E; Spriggs, D R; Beckett, M A; Kufe, D W; Weichselbaum, R R

    1989-01-01

    We report that tumor necrosis factor alpha (TNF-alpha) mRNA is increased after treatment with x-rays in certain human sarcoma cells. An increase in TNF-alpha mRNA is accompanied by the increased production of TNF-alpha protein. TNF-alpha enhances radiation lethality in both TNF-alpha-producing and -nonproducing tumor cells. These data suggest that, in addition to the direct cytotoxic effects of x-rays, production of TNF-alpha may add to radiation lethality through autocrine and paracrine mechanisms. Combinations of TNF-alpha and therapeutic radiation may be useful in clinical cancer therapy. Images PMID:2602359

  9. Mycobacterium tuberculosis PPE68 and Rv2626c genes contribute to the host cell necrosis and bacterial escape from macrophages.

    PubMed

    Danelishvili, Lia; Everman, Jamie; Bermudez, Luiz E

    2016-01-01

    Alveolar macrophages are the main line of innate immune response against M. tuberculosis (Mtb) infection. However, these cells serve as the major intracellular niche for Mtb enhancing its survival, replication and, later on, cell-to-cell spread. Mtb-associated cytotoxicity of macrophages has been well documented, but limited information exists about mechanisms by which the pathogen induces cell necrosis. To identify virulence factors involved in the induction of necrosis, we screened 5,000 transposon mutants of Mtb for clones that failed to promote the host cell necrosis in a similar manner as the wild-type bacterium. Five Mtb mutants were identified as potential candidates inducing significantly lower levels of THP-1 cell damage in contrast to the H37Rv wild-type infection. Reduced levels of the cell damage by necrosis deficient mutants (NDMs) were also associated with delayed damage of mitochondrial membrane permeability when compared with the wild-type infection over time. Two knockout mutants of the Rv3873 gene, encoding a cell wall PPE68 protein of RD1 region, were identified out of 5 NDMs. Further investigation lead to the observation that PPE68 protein interacts and exports several unknown or known surface/secreted proteins, among them Rv2626c is associated with the host cell necrosis. When the Rv2626c gene is deleted from the genome of Mtb, the bacterium displays significantly less necrosis in THP-1 cells and, conversely, the overexpression of Rv2626c promotes the host cell necrosis at early time points of infections in contrast to the wild-type strain.

  10. Model-Based Radiation Dose Correction for Yttrium-90 Microsphere Treatment of Liver Tumors With Central Necrosis

    SciTech Connect

    Liu, Ching-Sheng; Lin, Ko-Han; Lee, Rheun-Chuan; Tseng, Hsiou-Shan; Wang, Ling-Wei; Huang, Pin-I; Chao, Liung-Sheau; Chang, Cheng-Yen; Yen, Sang-Hue; Tung, Chuan-Jong; Wang, Syh-Jen; Oliver Wong, Ching-yee

    2011-11-01

    Purpose: The objectives of this study were to model and calculate the absorbed fraction {phi} of energy emitted from yttrium-90 ({sup 90}Y) microsphere treatment of necrotic liver tumors. Methods and Materials: The tumor necrosis model was proposed for the calculation of {phi} over the spherical shell region. Two approaches, the semianalytic method and the probabilistic method, were adopted. In the former method, the range--energy relationship and the sampling of electron paths were applied to calculate the energy deposition within the target region, using the straight-ahead and continuous-slowing-down approximation (CSDA) method. In the latter method, the Monte Carlo PENELOPE code was used to verify results from the first method. Results: The fraction of energy, {phi}, absorbed from {sup 90}Y by 1-cm thickness of tumor shell from microsphere distribution by CSDA with complete beta spectrum was 0.832 {+-} 0.001 and 0.833 {+-} 0.001 for smaller (r{sub T} = 5 cm) and larger (r{sub T} = 10 cm) tumors (where r is the radii of the tumor [T] and necrosis [N]). The fraction absorbed depended mainly on the thickness of the tumor necrosis configuration, rather than on tumor necrosis size. The maximal absorbed fraction {phi} that occurred in tumors without central necrosis for each size of tumor was different: 0.950 {+-} 0.000, and 0.975 {+-} 0.000 for smaller (r{sub T} = 5 cm) and larger (r{sub T} = 10 cm) tumors, respectively (p < 0.0001). Conclusions: The tumor necrosis model was developed for dose calculation of {sup 90}Y microsphere treatment of hepatic tumors with central necrosis. With this model, important information is provided regarding the absorbed fraction applicable to clinical {sup 90}Y microsphere treatment.

  11. Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

    SciTech Connect

    Levin, Victor A.; Bidaut, Luc; Hou, Ping; Kumar, Ashok J.; Wefel, Jeffrey S.; Bekele, B. Nebiyou; Prabhu, Sujit; Loghin, Monica; Gilbert, Mark R.; Jackson, Edward F.

    2011-04-01

    Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with

  12. The effect of chronic periodontitis on serum levels of tumor necrosis factor-alpha in Alzheimer disease

    PubMed Central

    Farhad, Shirin Zahra; Amini, Shahram; Khalilian, Amir; Barekatain, Majid; Mafi, Morvarid; Barekatain, Mehrdad; Rafei, Ehsan

    2014-01-01

    Background: Despite the outbreak in dental science, oral and dental complications in Alzheimer are of the unsolved problems. It is assumed that tumor necrosis factor-α, which is a key factor in Alzheimer, has a relation with periodontal complications in patients with Alzheimer disease. The present study evaluated the effect of chronic periodontitis on serum levels of tumor necrosis factor-α in Alzheimer disease. Materials and Methods: This case-control study was performed on 80 patients with Alzheimer disease seeking medical care at Nour Hospital, Isfahan, Iran. Eighty patients with Alzheimer disease between 40 and 70 years old attended this study. Forty had chronic periodontitis (case group), and 40 patients had healthy periodontium (control group). Blood sample was taken, and serum levels of tumor necrosis factor-α were measured by means of an ELISA Reader device. Independent T-Test was used to analyze data, and P < 0.05 was considered significant. Results: The mean of tumor necrosis factor-α was 749.1 ng/μL in case group and 286.8 ng/μL in control group. Independent t-test showed that the mean of tumor necrosis factor-α in patients with Alzheimer and periodontitis was approximately three folds higher than the patients only with Alzheimer, and this difference was statistically significant (P < 0.001). Conclusion: According to the results of this study, it seems that there is a difference between serum levels of tumor necrosis factor-α in patient with Alzheimer and chronic periodontitis and patients with Alzheimer disease and healthy periodontium. Tumor necrosis factor-α level in serum may act as a diagnostic marker of periodontal disease in patients with Alzheimer disease PMID:25426144

  13. Favorable Prognosis in Patients With High-Grade Glioma With Radiation Necrosis: The University of Colorado Reoperation Series

    SciTech Connect

    Rusthoven, Kyle E.; Olsen, Christine; Franklin, Wilbur; Kleinschmidt-DeMasters, B.K.; Kavanagh, Brian D.; Gaspar, Laurie E.; Lillehei, Kevin; Waziri, Allen; Damek, Denise M.; Chen, Changhu

    2011-09-01

    Purpose: To analyze the pathology, outcomes, and prognostic factors in patients with high-grade glioma undergoing reoperation after radiotherapy (RT). Methods and Materials: Fifty-one patients with World Health Organization Grade 3-4 glioma underwent reoperation after prior RT. The median dose of prior RT was 60 Gy, and 84% received chemotherapy as part of their initial treatment. Estimation of the percentage of necrosis and recurrent tumor in each reoperation specimen was performed. Pathology was classified as RT necrosis if {>=}80% of the specimen was necrotic and as tumor recurrence if {>=}20% was tumor. Predictors of survival were analyzed using log-rank comparisons and Cox proportional hazards regression. Results: The median interval between the completion of RT and reoperation was 6.7 months (range, 1-59 months). Pathologic analysis showed RT necrosis in 27% and recurrence in 73% of cases. Thirteen patients required a reoperation for uncontrolled symptoms. Among them, 1 patient (8%) had pathology showing RT necrosis, and 12 (92%) had tumor recurrence. Median survival after reoperation was longer for patients with RT necrosis (21.8 months vs. 7.0 months, p = 0.047). In 7 patients with Grade 4 tumors treated with temozolomide-based chemoradiation with RT necrosis, median survival from diagnosis and reoperation were 30.2 months and 21.8 months, respectively. Conclusions: Patients with RT necrosis at reoperation have improved survival compared with patients with tumor recurrence. Future efforts to intensify local therapy and increase local tumor control in patients with high-grade glioma seem warranted.

  14. Direct evidence for rapid and selective induction of tumor neovascular permeability by tumor necrosis factor and a novel derivative, colloidal gold bound tumor necrosis factor.

    PubMed

    Farma, Jeffrey M; Puhlmann, Markus; Soriano, Perry A; Cox, Derrick; Paciotti, Giulio F; Tamarkin, Lawrence; Alexander, H Richard

    2007-06-01

    Tumor necrosis factor (TNF) causes regression of advanced cancers when used in isolation perfusion with melphalan; evidence suggests these effects are mediated via selective yet uncharacterized actions on tumor neovasculature. A novel derivative, colloidal gold bound TNF (cAu-TNF) has been shown to have similar antitumor effects as native TNF with less systemic toxicity in mice. These studies were done to determine their effects on tumor neovasculature, using in vivo video microscopy. Female C57BL/6 mice bearing 20 mm(2) MC38 or LLC tumors that are TNF sensitive and resistant tumors, respectively, had dorsal skinfold chambers implanted. The rate of interstitial accumulation of Texas red fluorescently labeled albumin in tumor and normal vasculature was measured after intravenous TNF, cAu-TNF or PBS. Changes in interstitial fluorescent intensity over time were quantified as a reflection of alterations in vascular permeability. MC38 bearing mice treated with TNF or cAu-TNF demonstrated a rapid, selective and significant increase in tracer accumulation in areas of neovasculature compared to those of normal vasculature. Experiments in LLC tumor bearing mice showed similar results. Monoclonal antibody against tissue factor partially abrogated the effects of TNF on MC38 neovasculature. These data provide direct evidence that TNF and cAu-TNF selectively and rapidly alter permeability in tumor neovasculature; a phenomenon that may be exploited to enhance selective delivery of chemotherapeutics to tumor.

  15. Shedding of Tumor Necrosis Factor Receptor 1 Induced by Protein A Decreases Tumor Necrosis Factor Alpha Availability and Inflammation during Systemic Staphylococcus aureus Infection

    PubMed Central

    Giai, Constanza; Gonzalez, Cintia; Ledo, Camila; Garofalo, Ailin; Di Genaro, María Silvia; Sordelli, Daniel O.

    2013-01-01

    Staphylococcus aureus infections are an important public health concern due to their increasing incidence and high rates of mortality. The success of S. aureus as a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of tumor necrosis factor alpha (TNF-α) in the initial host defense against systemic staphylococcal infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients. S. aureus protein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-α receptor 1 (TNFR1). In this study, we demonstrate that S. aureus, via protein A-mediated signaling, induces early shedding of TNFR1, which precedes the secretion of TNF-α in vitro and in vivo. The results obtained using a protein A-deficient mutant and tnfr1−/− mice strongly suggest that the increased levels of soluble TNFR1 present during experimental S. aureus infection may neutralize circulating TNF-α and impair the host inflammatory response. Early shedding of TNFR1 induced by protein A may constitute a novel mechanism by which S. aureus subverts the host immune response. PMID:24002060

  16. Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo.

    PubMed Central

    Van Zee, K J; Kohno, T; Fischer, E; Rock, C S; Moldawer, L L; Lowry, S F

    1992-01-01

    Tumor necrosis factor alpha (TNF alpha), a primary mediator of systemic responses to sepsis and infection, can be injurious to the organism when present in excessive quantities. Here we report that two types of naturally occurring soluble TNF receptors (sTNFR-I and sTNFR-II) circulate in human experimental endotoxemia and in critically ill patients and demonstrate that they neutralize TNF alpha-induced cytotoxicity and immunoreactivity in vitro. Utilizing immunoassays that discriminate between total sTNFR-I and sTNFR-I not bound to TNF alpha, we show that sTNFR-I-TNF alpha complexes may circulate even in the absence of detectable free TNF alpha. To investigate the therapeutic possibilities of sTNFR-I, recombinant protein was administered to nonhuman primates with lethal bacteremia and found to attenuate hemodynamic collapse and cytokine induction. We conclude that soluble receptors for TNF alpha are inducible in inflammation and circulate at levels sufficient to block the in vitro cytotoxicity associated with TNF alpha levels observed in nonlethal infection. Administration of sTNFR-I can prevent the adverse pathologic sequelae caused by the exaggerated TNF alpha production observed in lethal sepsis. Images PMID:1317575

  17. Fat Embolism Syndrome Secondary to Bone Marrow Necrosis in Patients with Hemoglobinopathies.

    PubMed

    Gangaraju, Radhika; Reddy, Vishnu V B; Marques, Marisa B

    2016-09-01

    Bone marrow necrosis with subsequent embolization of the fat and necrotic tissues into the systemic circulation causing fat embolism syndrome and multiorgan failure is a rare complication of patients with hemoglobinopathies. The exact etiology of this condition is not known. Because it occurs more often in patients with compound heterozygous conditions than in sickle cell disease, some patients are unaware of their predisposition. The initial symptoms are nonspecific, such as back and/or abdominal pain, fever, and fatigue, which may rapidly progress to respiratory failure and severe neurologic compromise. Common laboratory tests reveal anemia without reticulocytosis, thrombocytopenia, leukoerythroblastic picture with immature white cells and nucleated red blood cells, increased lactate dehydrogenase, high ferritin, and, sometimes increased creatinine. The diagnosis can be delayed because of an apparent lack of awareness about bone marrow necrosis with fat embolism syndrome, its rarity, and its similarities with other conditions such as thrombotic thrombocytopenic purpura. Although a bone marrow biopsy is diagnostic, waiting for it delays definitive treatment, which appears to be essential for the recovery of end-organ damage, such as neurologic and pulmonary damage. In our experience, either multiple units of red blood cell transfusion or, preferably, red cell exchange initiated promptly, is lifesaving. PMID:27598359

  18. Late preventive effects of trifluoperazine on carbon tetrachloride-induced hepatic necrosis

    SciTech Connect

    Villarruel, M.C.; Fernandez, G.; de Ferreyra, E.C.; de Fenos, O.M.; Castro, J.A.

    1986-04-01

    As a very preliminary test for a possible role of calmodulin in CCl/sub 4/-induced hepatic injury, we studied the effects of the anticalmodulin drug trifluoperazine (TFP) on several deleterious actions of CCl/sub 4/ on the liver. TFP administrated 30 min before or 6 or 10 hr after CCl/sub 4/ significantly prevented hepatic necrosis induced by the hepatotoxin at 24 hr but not at 72 hr. TFP did not modify the CCl/sub 4/ concentrations reaching the liver, or the intensity of the covalent binding of CCl/sub 4/-reactive metabolites to hepatic microsomal proteins or lipids or the CCl/sub 4/-induced cytochrome P-450 and glucose 6 phosphatase destruction. TFP administration decreased body temperature between 0 and 1 degree C in controls and between 1.2 and 3.5 degrees C in CCl/sub 4/-treated animals during the 24-hr observation period. When TFP-treated CCl/sub 4/-poisoned animals were kept normothermic, protective effects were eliminated. One possibility is that the protective effect of TFP might be due to a nonspecific action related to decreased body temperature. Alternatively, prevention might result from TFP inhibition of a late-occurring process critical for CCl/sub 4/-induced cell necrosis requiring calmodulin participation. If this alternative were in operation, protective consequences of this inhibitory effect of TFP should be either canceled or counteracted in the normothermic TFP + CCl/sub 4/-treated animal.

  19. Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green

    PubMed Central

    Fang, Cheng; Wang, Kun; Zeng, Chaoting; Chi, Chongwei; Shang, Wenting; Ye, Jinzuo; Mao, Yamin; Fan, Yingfang; Yang, Jian; Xiang, Nan; Zeng, Ning; Zhu, Wen; Fang, Chihua; Tian, Jie

    2016-01-01

    Tissue necrosis commonly accompanies the development of a wide range of serious diseases. Therefore, highly sensitive detection and precise boundary delineation of necrotic tissue via effective imaging techniques are crucial for clinical treatments; however, no imaging modalities have achieved satisfactory results to date. Although fluorescence molecular imaging (FMI) shows potential in this regard, no effective necrosis-avid fluorescent probe has been developed for clinical applications. Here, we demonstrate that indocyanine green (ICG) can achieve high avidity of necrotic tissue owing to its interaction with lipoprotein (LP) and phospholipids. The mechanism was explored at the cellular and molecular levels through a series of in vitro studies. Detection of necrotic tissue and real-time image-guided surgery were successfully achieved in different organs of different animal models with the help of FMI using in house-designed imaging devices. The results indicated that necrotic tissue with a 0.6 mm diameter could be effectively detected with precise boundary definition. We believe that the new discovery and the associated imaging techniques will improve personalized and precise surgery in the near future. PMID:26864116

  20. Platelets support a protective immune response to LCMV by preventing splenic necrosis

    PubMed Central

    Loria, Gilbert David; Romagnoli, Pablo A.; Moseley, Nelson B.; Rucavado, Alexandra

    2013-01-01

    Severe arenaviral infections in humans are characterized by clinical findings common to other viral hemorrhagic fevers (VHFs), including thrombocytopenia, leukopenia, skin and internal organ hemorrhages, high viral replication, splenic necrosis, and death. Host responses, rather than direct damage by the arenaviral replication, account for most of the observed pathology, but it is not known what protective roles platelets may have in each of the manifestations. To address this issue in an animal model, we compared nondepleted (100%), partially depleted (15%), and profoundly (< 2.5%) platelet-depletedmice infected with the mouse arenavirus lymphocytic choriomeningitis virus (LCMV). Here, we describe that systemic bleedings and death were seen only in those animals receiving the stronger depletion treatment. Furthermore, we showed that the nonhemorrhagic but partially platelet-depleted mice were unable to control the viral replication because of generalized splenic necrosis, affecting innate and adaptive immune cells. These data suggest that, by their supportive roles in hemostasis, platelets may be preventing the severe pathology observed in human arenaviral infections. PMID:22566603

  1. Bean Common Mosaic Virus and Bean Common Mosaic Necrosis Virus: Relationships, Biology, and Prospects for Control.

    PubMed

    Worrall, Elizabeth A; Wamonje, Francis O; Mukeshimana, Gerardine; Harvey, Jagger J W; Carr, John P; Mitter, Neena

    2015-01-01

    The closely related potyviruses Bean common mosaic virus (BCMV) and Bean common mosaic necrosis virus (BCMNV) are major constraints on common bean (Phaseolus vulgaris) production. Crop losses caused by BCMV and BCMNV impact severely not only on commercial scale cultivation of this high-value crop but also on production by smallholder farmers in the developing world, where bean serves as a key source of dietary protein and mineral nutrition. In many parts of the world, progress has been made in combating BCMV through breeding bean varieties possessing the I gene, a dominant gene conferring resistance to most BCMV strains. However, in Africa, and in particular in Central and East Africa, BCMNV is endemic and this presents a serious problem for deployment of the I gene because this virus triggers systemic necrosis (black root disease) in plants possessing this resistance gene. Information on these two important viruses is scattered throughout the literature from 1917 onward, and although reviews on resistance to BCMV and BCMNV exist, there is currently no comprehensive review on the biology and taxonomy of BCMV and BCMNV. In this chapter, we discuss the current state of our knowledge of these two potyviruses including fundamental aspects of classification and phylogeny, molecular biology, host interactions, transmission through seed and by aphid vectors, geographic distribution, as well as current and future prospects for the control of these important viruses.

  2. Immunological effects of a tumor necrosis factor alpha-armed oncolytic adenovirus.

    PubMed

    Hirvinen, Mari; Rajecki, Maria; Kapanen, Mika; Parviainen, Suvi; Rouvinen-Lagerström, Noora; Diaconu, Iulia; Nokisalmi, Petri; Tenhunen, Mikko; Hemminki, Akseli; Cerullo, Vincenzo

    2015-03-01

    For long it has been recognized that tumor necrosis factor alpha (TNFa) has anticancer characteristics, and its use as a cancer therapeutic was proposed already in the 1980s. However, its systemic toxicity has limited its usability. Oncolytic viruses, selectively cancer-killing viruses, have shown great potency, and one of their most useful aspects is their ability to produce high amounts of transgene products locally, resulting in high local versus systemic concentrations. Therefore, the overall magnitude of tumor cell killing results from the combination of oncolysis, transgene-mediated direct effect such as TNFa-mediated apoptosis, and, perhaps most significantly, from activation of the host immune system against the tumor. We generated a novel chimeric oncolytic adenovirus expressing human TNFa, Ad5/3-D24-hTNFa, whose efficacy and immunogenicity were tested in vitro and in vivo. The hTNFa-expressing adenovirus showed increased cancer-eradicating potency, which was shown to be because of elevated apoptosis and necrosis rates and induction of various immune responses. Interestingly, we saw increase in immunogenic cell death markers in Ad5/3-d24-hTNFa-treated cells. Moreover, tumors treated with Ad5/3-D24-hTNFa displayed enhanced presence of OVA-specific cytotoxic T cells. We thus can conclude that tumor eradication and antitumor immune responses mediated by Ad5/3-d24-hTNFa offer a new potential drug candidate for cancer therapy.

  3. Immediate free jejunum transfer for salvage surgery of gastric tube necrosis.

    PubMed

    Umezawa, Hiroki; Matsutani, Takeshi; Ogawa, Rei; Hyakusoku, Hiko

    2014-01-01

    Gastric tube necrosis after esophagus cancer surgery is a rare but critical situation. Salvage reconstruction of the esophagus remains a challenging procedure for head and neck surgeons. Historically, surgeons have employed a two-stage salvage surgery consisting of debridement followed by reconstruction. While this procedure generates good results, the time to restart oral alimentation is long. The present report describes the case of a 62-year-old male who developed gastric tube necrosis 3 days after undergoing surgery for thoracic-cervical esophageal cancer and immediate reconstruction with the retrosternal gastric pullup technique. He was treated with debridement and simultaneous free jejunum transfer 4 days after the primary surgery. He was able to restart oral alimentation 10 days after the salvage surgery. This rapid return to oral alimentation is a major advantage of the one-stage immediate esophagus salvage reconstruction. Another advantage is the ease of the reconstructive procedure: the absence of scarring and prolonged inflammation, which are disadvantages of the two-stage procedure, meant that recipient vessel selection and anastomosis were uncomplicated. The one-step procedure may be particularly useful in cases where the inflammation is discovered early.

  4. Polybrene: Observations on cochlear hair cell necrosis and minimal lentiviral transduction of cochlear hair cells.

    PubMed

    Han, Miaomiao; Yu, Dongzhen; Song, Qiang; Wang, Jiping; Dong, Pin; He, Jingchun

    2015-07-23

    Polybrene is widely used to enhance viral transduction; however, little is known about the utility thereof, in enhancing lentiviral transduction of cochlear cells. In the present study, we examined the cytotoxic effects of polybrene, and the further effects thereof, on lentiviral transduction of cochlear cells, especially sensory hair cells. Cochlear basilar membranes of newborn rats were cultured and treated with 0.1-10 μg/mL polybrene for 24h to explore the potential development of ototoxicity. PI staining and TUNEL detection were used to evaluate necrosis or apoptosis of hair cell. Various doses of lentivirus-GFP were added to cochlear organotypic cultures with safe concentrations of polybrene, incubated for 24h, and cultured (in the absence of the virus and polybrene) for a further 48 h. Transduction efficiencies were evaluated. The results showed that polybrene at 0.1 μg/mL was safe to cochlear cells, and 0.5-10 μg/mL concentration induced hair cell necrosis in a dose-dependent manner. However, supporting cells were not damaged. Lentiviral vectors transduced into cochlear cells and 0.1 μg/mL polybrene enhanced transduction efficiency. However, hair cells were hardly transduced with lentiviral vectors either alone or in the presence of 0.1 μg/mL polybrene. The use of polybrene to aid lentiviral transduction of cochlear hair cells requires further attention.

  5. Polybrene: Observations on cochlear hair cell necrosis and minimal lentiviral transduction of cochlear hair cells.

    PubMed

    Han, Miaomiao; Yu, Dongzhen; Song, Qiang; Wang, Jiping; Dong, Pin; He, Jingchun

    2015-07-23

    Polybrene is widely used to enhance viral transduction; however, little is known about the utility thereof, in enhancing lentiviral transduction of cochlear cells. In the present study, we examined the cytotoxic effects of polybrene, and the further effects thereof, on lentiviral transduction of cochlear cells, especially sensory hair cells. Cochlear basilar membranes of newborn rats were cultured and treated with 0.1-10 μg/mL polybrene for 24h to explore the potential development of ototoxicity. PI staining and TUNEL detection were used to evaluate necrosis or apoptosis of hair cell. Various doses of lentivirus-GFP were added to cochlear organotypic cultures with safe concentrations of polybrene, incubated for 24h, and cultured (in the absence of the virus and polybrene) for a further 48 h. Transduction efficiencies were evaluated. The results showed that polybrene at 0.1 μg/mL was safe to cochlear cells, and 0.5-10 μg/mL concentration induced hair cell necrosis in a dose-dependent manner. However, supporting cells were not damaged. Lentiviral vectors transduced into cochlear cells and 0.1 μg/mL polybrene enhanced transduction efficiency. However, hair cells were hardly transduced with lentiviral vectors either alone or in the presence of 0.1 μg/mL polybrene. The use of polybrene to aid lentiviral transduction of cochlear hair cells requires further attention. PMID:26071903

  6. [Free microvascular transfer of segmental corticocancellous femur for treatment of avascular scaphoid necrosis].

    PubMed

    Bürger, K H; Gaggl, A J; Kukutschki, W; Mueller, E

    2009-02-01

    Successful treatment of scaphoid non-union with avascular necrosis of the proximal poles and humpback deformity with carpal collapse is one of the main problems in reconstructive hand surgery. Vascularised bone transfer is one of the most successful techniques for treating these problems. 15 patients with avascular necrosis and non-union of the scaphoid were treated by a microvascular reanastomosed corticocancellous transplant from the distal medial femur. In all patients the success of the microvascular bone transfer was examined by MRI and conventional radiographs immediately, 6 weeks, 3, 6 and 12 months postoperatively. The transplant vitality, signs of reunion and carpal configuration were registered. Furthermore, the Mayo wrist score was employed for clinical evaluation. All transplants remained vital during the follow-up period of one year. Pseudoarthrosis was treated successfully in every case. In 14 cases there was a significant increase of the Mayo wrist score and in one case there was no difference before and after surgery. The microvascular transfer of corticocancellous femur resulted in a high rate of complete healing of scaphoid pseudoarthrosis and correction of the carpal relation.

  7. [Micrococcus sp.--the pathogen of leaf necrosis of horse-chestnuts (Aesculus L.) in Kiev].

    PubMed

    Iakovleva, L M; Makhinia, L V; Shcherbina, T N; Ogorodnik, L E

    2013-01-01

    A group of phytopathogenic bacteria was isolated from patterns of drying horse-chestnuts (Aesculus L.), which grow in Kyiv. The properties of slowly growing, highly aggressive microorganisms have been described in the paper. They grow up on the 8-10th day after sowing. The investigated microorganisms form very small (0.5-1 mm in diameter) colonies on the potato agar. Bacteria are protuberant, shining, smooth with flat edges, they are pale yellow, yellow, or pink. The bacteria are Gram-positive, spherical, are disposed in smears singly, in pairs, as accumulations, or netting. They are aerobes, do not form spores, are not mobile. They are inert in respect of different sources of carbon. They reduce nitrates, do not dilute gelatin, do not hydrolyze starch, do not release hydrogen sulphide and indole. The bacteria are catalase-positive, oxidase-negative. They do not cause potato and carrot rot. They lose quickly their viability under the laboratory conditions. The saturated acids C 14:0; C 15:0; C16:0; C18:0 have been revealed in the composition of cellular fatty acids. Microorganisms are identified as Micrococcus sp. Under artificial inoculation this highly aggressive pathogen causes drying of the horse-chestnut buds and necrosis, which occupies 1/3-1/2 of the leaf plate. A wide zone of chlorosis, surrounding necrosis, may occupy the whole leaf surface. The infected leaves use to twist up from the top (apex) or along a midrib and to dry.

  8. Experimental and analytical investigation of the thermal necrosis in high-speed drilling of bone.

    PubMed

    Shakouri, Ehsan; Sadeghi, Mohammad H; Maerefat, Mehdi; Shajari, Shaghayegh

    2014-04-01

    Bone loss due to thermo necrosis may weaken the purchase of surgically placed screws and pins, causing them to loosen postoperatively. The heat generated during the bone drilling is proportional to cutting speed and force and may be partially dissipated by the blood and tissue fluids, and somehow carried away by the chips formed. Increasing cutting speed will reduce cutting force and machining time. Therefore, it is of interest to study the effects of the increasing cutting speed on bone drilling characteristics. In this article, the effects of the increasing cutting speed ranging from 500 up to 18,000 r/min on the thrust force and the temperature rise are studied for bovine femur bone. The results of this study reveal that the high-speed drilling of 6000-7000 r/min may effectively reduce the two parameters of maximum cortical temperature and duration of exposure at temperatures above the allowable levels, which in turn reduce the probability of thermal necrosis in the drill site. This is due to the reduction of the cutting force and the increase in the chip disposal speed. However, more increases in the drill bit rotational speed result in an increase in the amount of temperature elevation, not because of sensible change in drilling force but a considerable increase in friction among the chips, drill bit and the hole walls.

  9. Fundus autofluorescence and optical coherence tomography in the management of progressive outer retinal necrosis

    PubMed Central

    Yeh, Steven; Wong, Wai T.; Weichel, Eric D.; Lew, Julie C.; Chew, Emily Y.; Nussenblatt, Robert B.

    2011-01-01

    A 41 year-old female patient with acquired immune deficiency syndrome (AIDS) presented with progressive nasal visual field loss in her right eye. Ophthalmic exam revealed widespread areas of retinal opacification with hemorrhage consistent with progressive outer retinal necrosis (PORN), which was confirmed by polymerase chain reaction (PCR) for varicella zoster virus (VZV) DNA. The patient was treated with intravenous and intravitreal foscarnet and ganciclovir with a resultant improvement clinically. Optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging revealed progressive changes indicative of widespread retinal pigment epithelial (RPE) and outer retinal dysfunction. OCT was useful in documenting progressive changes in macular architecture during therapy including neurosensory elevation, cystoid macular edema, and severe outer retinal necrosis, at initial exam, 1 week, and 1 month follow-up. Fundus autofluorescence revealed areas of stippled, hyperfluorescence within extensive zones of hypofluorescence, which progressed during the follow-up period. These areas appeared to represent lipofuscin or its photoreactive components within larger regions of RPE loss. The combination of OCT and FAF was useful in the characterization of the RPE and retinal anatomy in this patient with PORN. PMID:20337261

  10. Structural and functional alterations of catalase induced by acriflavine, a compound causing apoptosis and necrosis.

    PubMed

    Attar, Farnoosh; Khavari-Nejad, Sarah; Keyhani, Jacqueline; Keyhani, Ezzatollah

    2009-08-01

    Acriflavine is an antiseptic agent causing both apoptosis and necrosis in yeast. In this work, its effect on the structure and function of catalase, a vital enzyme actively involved in protection against oxidative stress, was investigated. In vitro kinetic studies showed that acriflavine inhibited the enzymatic activity in a competitive manner. The residual activity detectable after preincubation of catalase (1.5 nmol/L) with various concentrations of acriflavine went from 50% to 20% of the control value as the acriflavine concentration increased from 30 to 90 micromol/L. Correlatively with the decrease in activity, alterations in the enzyme's conformation were observed as indicated by fluorescence spectroscopy, circular dichroism spectroscopy, and electronic absorption spectroscopy. The enzyme's intrinsic fluorescence obtained upon excitation at either 297 nm (tryptophan residues) or 280 nm (tyrosine and tryptophan residues) decreased as a function of acriflavine concentration. Circular dichroism studies showed alterations of the protein structure by acriflavine with up to 13% decrease in alpha helix, 16% increase in beta-sheet content, 17% increase in random coil, and 4% increase in beta turns. Spectrophotometric studies showed a blueshift and modifications in the chromicity of catalase at 405 nm, corresponding to an absorbance band due to the enzyme's prosthetic group. Thus, acriflavine induced in vitro a profound change in the structure of catalase so that the enzyme could no longer function. Our results showed that acriflavine, a compound producing apoptosis and necrosis, can have a direct effect on vital functions in cells by disabling key enzymes.

  11. Chlorhexidine-induced apoptosis or necrosis in L929 fibroblasts: A role for endoplasmic reticulum stress

    SciTech Connect

    Faria, Gisele; Cardoso, Cristina R.B.; Larson, Roy E.; Silva, Joao S.; Rossi, Marcos A.

    2009-01-15

    Chlorhexidine (CHX), widely used as antiseptic and therapeutic agent in medicine and dentistry, has a toxic effect both in vivo and in vitro. The intrinsic mechanism underlying CHX-induced cytotoxicity in eukaryotic cells is, however, still unknown. A recent study from our laboratory has suggested that CHX may induce death in cultured L929 fibroblasts via endoplasmic reticulum (ER) stress. This hypothesis was further tested by means of light and electron microscopy, quantification of apoptosis and necrosis by flow cytometry, fluorescence visualization of the cytoskeleton and endoplasmic reticulum, and evaluation of the expression of 78-kDa glucose-regulated protein 78 (Grp78), a marker of activation of the unfolded protein response (UPR) in cultured L929 fibroblasts. Our finding showing increased Grp 78 expression in CHX-treated cells and the results of flow cytometry, cytoskeleton and endoplasmic reticulum fluorescence visualization, and scanning and transmission electron microscopy allowed us to suggest that CHX elicits accumulation of proteins in the endoplasmic reticulum, which causes ER overload, resulting in ER stress and cell death either by necrosis or apoptosis. It must be pointed out, however, that this does not necessarily mean that ER stress is the only way that CHX kills L929 fibroblasts, but rather that ER stress is an important target or indicator of cell death induced by this drug.

  12. Interleukin-10 and tumour necrosis factor-alpha serum levels in chronic Chagas disease patients.

    PubMed

    Vasconcelos, R H T; Azevedo, E de A N; Diniz, G T N; Cavalcanti, M da G A de M; de Oliveira, W; de Morais, C N L; Gomes, Y de M

    2015-07-01

    In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin-10 and tumour necrosis factor-alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin-10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor-alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow-up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease.

  13. Polymer-conjugated inhibitors of tumor necrosis factor-α for local control of inflammation

    PubMed Central

    Washburn, Newell R.; Prata, Joseph E.; Friedrich, Emily E.; Ramadan, Mohamed H.; Elder, Allison N.; Sun, Liang Tso

    2013-01-01

    Burns, chronic wounds, osteoarthritis, and uveitis are examples of conditions characterized by local, intense inflammatory responses that can impede healing or even further tissue degradation. The most powerful anti-inflammatory drugs available are often administered systemically, but these carry significant side effects and are not compatible for patients that have underlying complications associated with their condition. Conjugation of monoclonal antibodies that neutralize pro-inflammatory cytokines to high molecular weight hydrophilic polymers has been shown to be an effective strategy for local control of inflammation. Lead formulations are based on antibody inhibitors of tumor necrosis factor-α conjugated to hyaluronic acid having molecular weight greater than 1 MDa. This review will discuss fundamental aspects of medical conditions that could be treated with these conjugates and design principles for preparing these cytokine-neutralizing polymer conjugates. Results demonstrating that infliximab, an approved inhibitor of tumor necrosis factor-α, can be incorporated into the conjugates using a broad range of water-soluble polymers are also presented, along with a prospectus for clinical translation. PMID:23903893

  14. A zebrafish (Danio rerio) model of infectious spleen and kidney necrosis virus (ISKNV) infection

    SciTech Connect

    Xu Xiaopeng; Zhang Lichun; Weng Shaoping; Huang Zhijian; Lu Jing; Lan Dongming; Zhong Xuejun; Yu Xiaoqiang; Xu Anlong He Jianguo

    2008-06-20

    Zebrafish is a model animal for studies of genetics, development, toxicology, oncology, and immunology. In this study, infectious spleen and kidney necrosis virus (ISKNV) was used to establish an infection in zebrafish, and the experimental conditions were established and characterized. Mortality of adult zebrafish infected with ISKNV by intraperitoneal (i.p.) injection exceeded 60%. ISKNV can be passed stably in zebrafish for over ten passages. The ailing zebrafish displayed petechial hemorrhaging and scale protrusion. Histological analysis of moribund fish revealed necrosis of tissue and enlarged cells in kidney and spleen. The real-time RT-PCR analysis of mRNA level confirmed that ISKNV was replicated in zebrafish. Immunohistochemistry and immunofluorescence analyses further confirmed the presence of ISKNV-infected cells in almost all organs of the infected fish. Electron microscope analyses showed that the ISKNV particle was present in the infected tissues. The establishment of zebrafish infection model of ISKNV can offer a valuable tool for studying the interactions between ISKNV and its host.

  15. Effects of clay on fat necrosis and carcass characteristics in Japanese Black steers.

    PubMed

    Oka, Akio; Iwamoto, Eiji; Tatsuda, Ken

    2015-10-01

    Twenty 10-month-old Japanese Black steers were used to evaluate the effects of clay on fat necrosis and carcass characteristics. Ten steers (Clay group) were fed the clay (50 g/day) during 10-30 months of age. The other 10 steers (Control group) were not fed it. There was no significant difference in body weight or average daily gain between the two groups (P > 0.05). The occurrence of fat necrotic mass in the Clay group (30%) was lower (P < 0.05) than that in the Control group (90%) at slaughter. The size of necrotic masses in the Clay group was smaller (P < 0.05) than that in the Control group. There was no significant difference in the marbling score, beef color, Longissimus muscle area or subcutaneous fat thickness between the two groups. These results suggest that the clay prevented the occurrence of fat necrosis and did not affect the carcass characteristics in Japanese Black steers.

  16. Fulminant bilateral acute retinal necrosis syndrome associated with viral encephalitis: A case report

    PubMed Central

    Zhou, Chunkui; Zhu, Lijun; Fang, Shaokuan

    2016-01-01

    Herpes simplex virus (HSV) is the most common cause of acute viral encephalitis. Acute retinal necrosis (ARN) is a rapidly progressing and potentially blinding eye disease that may be induced by HSV. The present case study reports the very rare case of a patient with herpes simplex encephalitis (HSE) combined with acute retinal necrosis (ARN). A 47-year-old woman was admitted to hospital with persistent high fever and somnolence for 5 days. Magnetic resonance imaging showed abnormal signals in the right medial temporal lobes, and HSV-1 was identified in the serum and cerebrospinal fluid. Five days later, despite treatment with intravenous acyclovir and partial improvement in consciousness, the patient suddenly developed blurred vision and bilateral visual pain. Fundus fluorescence angiography revealed bilateral vessel obstruction and flaky reduced fluorescence. ARN was diagnosed clinically. Dexamethasone was administered as an anti-inflammatory adjunct to intravenous acyclovir therapy. The visual acuity of the patient was reduced to mere light perception a further 4 days later. The present case indicates that HSE may be complicated with ARN, causing a reduction in visual acuity to mere light perception within a very short time.

  17. Chromosome damage, apoptosis, and necrosis in exfoliated cells of oral mucosa from androgenic anabolic steroids users.

    PubMed

    Souza, Jeanderson Pereira; Cerqueira, Eneida de Moraes Marcílio; Meireles, José Roberto Cardoso

    2015-01-01

    The aim of this study was to evaluate the potential of the androgenic anabolic steroids (AAS) for inducing chromosome damage, apoptosis, and necrosis, using the micronucleus test on exfoliated cells from the oral mucosa of AAS users. The sample consisted of 55 male individuals, practitioners of physical exercise divided into two groups: 25 individuals who were users of AAS and 30 individuals in the control group. Cytological analysis included, in addition to micronuclei, counting of broken eggs and degenerative nuclear changes indicative of apoptosis (karyorrhexis, condensed chromatin, and pyknosis) and necrosis (karyolysis in addition to these changes). The statistical analysis did not show differences in occurrences of micronuclei, karyolysis, and broken eggs between the groups. The occurrence of apoptosis was significantly higher in cells from control subjects. The results obtained showed that inhibition of apoptosis was induced by AAS, suggesting that this may be one of the mechanisms contributing toward the association that has been described between use of AAS and the carcinogenic process.

  18. Pathogenesis of infectious hematopoietic necrosis virus in adult sockeye salmon (Oncorhynchus nerka)

    USGS Publications Warehouse

    Mulcahy, D.M.; Burke, J.; Pascho, R.J.; Jenes, C.K.

    1982-01-01

    The concentration of infectious hematopoietic necrosis (IHN) virus was determined in eight organs and two body fluids from each of 60 adult sockeye salmon (Oncorhynchus nerka). Included in the sample were 4 males and 56 prespawning, spawning, or spent female fish. All fish were infected, and virus was present in nearly all organs. There was an overall tendency for the mean concentration to increase in many of the organs over time as the fish progressed in ripeness. In prespawning females, IHN virus could be detected in all organs and in ovarian fluid but not in serum; the incidences were highest in the gills, spleen, and pyloric ceca, and the titers were highest in the pyloric ceca and liver. Incidences of infection in the organs were higher in spawning than in prespawning females and higher still in spent females in which the incidence of virus was 100% in all organs except brains (78%) and sera (67%). Virus concentrations in organs or fluids ranged from 5 to 4.0 × 109 plaque-forming units per millilitre. In males, the highest incidences of virus were found in gills, pyloric ceca, and liver. The gills were the only organ in which the virus concentration in males exceeded that of females.Key words: infectious hematopoietic necrosis, IHN, fish virus, viral pathogenesis, sockeye salmon

  19. Fulminant bilateral acute retinal necrosis syndrome associated with viral encephalitis: A case report

    PubMed Central

    Zhou, Chunkui; Zhu, Lijun; Fang, Shaokuan

    2016-01-01

    Herpes simplex virus (HSV) is the most common cause of acute viral encephalitis. Acute retinal necrosis (ARN) is a rapidly progressing and potentially blinding eye disease that may be induced by HSV. The present case study reports the very rare case of a patient with herpes simplex encephalitis (HSE) combined with acute retinal necrosis (ARN). A 47-year-old woman was admitted to hospital with persistent high fever and somnolence for 5 days. Magnetic resonance imaging showed abnormal signals in the right medial temporal lobes, and HSV-1 was identified in the serum and cerebrospinal fluid. Five days later, despite treatment with intravenous acyclovir and partial improvement in consciousness, the patient suddenly developed blurred vision and bilateral visual pain. Fundus fluorescence angiography revealed bilateral vessel obstruction and flaky reduced fluorescence. ARN was diagnosed clinically. Dexamethasone was administered as an anti-inflammatory adjunct to intravenous acyclovir therapy. The visual acuity of the patient was reduced to mere light perception a further 4 days later. The present case indicates that HSE may be complicated with ARN, causing a reduction in visual acuity to mere light perception within a very short time. PMID:27698716

  20. Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green.

    PubMed

    Fang, Cheng; Wang, Kun; Zeng, Chaoting; Chi, Chongwei; Shang, Wenting; Ye, Jinzuo; Mao, Yamin; Fan, Yingfang; Yang, Jian; Xiang, Nan; Zeng, Ning; Zhu, Wen; Fang, Chihua; Tian, Jie

    2016-02-11

    Tissue necrosis commonly accompanies the development of a wide range of serious diseases. Therefore, highly sensitive detection and precise boundary delineation of necrotic tissue via effective imaging techniques are crucial for clinical treatments; however, no imaging modalities have achieved satisfactory results to date. Although fluorescence molecular imaging (FMI) shows potential in this regard, no effective necrosis-avid fluorescent probe has been developed for clinical applications. Here, we demonstrate that indocyanine green (ICG) can achieve high avidity of necrotic tissue owing to its interaction with lipoprotein (LP) and phospholipids. The mechanism was explored at the cellular and molecular levels through a series of in vitro studies. Detection of necrotic tissue and real-time image-guided surgery were successfully achieved in different organs of different animal models with the help of FMI using in house-designed imaging devices. The results indicated that necrotic tissue with a 0.6 mm diameter could be effectively detected with precise boundary definition. We believe that the new discovery and the associated imaging techniques will improve personalized and precise surgery in the near future.

  1. Interleukin 1 and Tumor Necrosis Factor Inhibit Cardiac Myocyte β -adrenergic Responsiveness

    NASA Astrophysics Data System (ADS)

    Gulick, Tod; Chung, Mina K.; Pieper, Stephen J.; Lange, Louis G.; Schreiner, George F.

    1989-09-01

    Reversible congestive heart failure can accompany cardiac allograft rejection and inflammatory myocarditis, conditions associated with an immune cell infiltrate of the myocardium. To determine whether immune cell secretory products alter cardiac muscle metabolism without cytotoxicity, we cultured cardiac myocytes in the presence of culture supernatants from activated immune cells. We observed that these culture supernatants inhibit β -adrenergic agonist-mediated increases in cultured cardiac myocyte contractility and intracellular cAMP accumulation. The myocyte contractile response to increased extracellular Ca2+ concentration is unaltered by prior exposure to these culture supernatants, as is the increase in myocyte intracellular cAMP concentration in response to stimulation with forskolin, a direct adenyl cyclase activator. Inhibition occurs in the absence of alteration in β -adrenergic receptor density or ligand binding affinity. Suppressive activity is attributable to the macrophage-derived cytokines interleukin 1 and tumor necrosis factor. Thus, these observations describe a role for defined cytokines in regulating the hormonal responsiveness and function of contractile cells. The effects of interleukin 1 and tumor necrosis factor on intracellular cAMP accumulation may be a model for immune modulation of other cellular functions dependent upon cyclic nucleotide metabolism. The uncoupling of agonist-occupied receptors from adenyl cyclase suggests that β -receptor or guanine nucleotide binding protein function is altered by the direct or indirect action of cytokines on cardiac muscle cells.

  2. Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green.

    PubMed

    Fang, Cheng; Wang, Kun; Zeng, Chaoting; Chi, Chongwei; Shang, Wenting; Ye, Jinzuo; Mao, Yamin; Fan, Yingfang; Yang, Jian; Xiang, Nan; Zeng, Ning; Zhu, Wen; Fang, Chihua; Tian, Jie

    2016-01-01

    Tissue necrosis commonly accompanies the development of a wide range of serious diseases. Therefore, highly sensitive detection and precise boundary delineation of necrotic tissue via effective imaging techniques are crucial for clinical treatments; however, no imaging modalities have achieved satisfactory results to date. Although fluorescence molecular imaging (FMI) shows potential in this regard, no effective necrosis-avid fluorescent probe has been developed for clinical applications. Here, we demonstrate that indocyanine green (ICG) can achieve high avidity of necrotic tissue owing to its interaction with lipoprotein (LP) and phospholipids. The mechanism was explored at the cellular and molecular levels through a series of in vitro studies. Detection of necrotic tissue and real-time image-guided surgery were successfully achieved in different organs of different animal models with the help of FMI using in house-designed imaging devices. The results indicated that necrotic tissue with a 0.6 mm diameter could be effectively detected with precise boundary definition. We believe that the new discovery and the associated imaging techniques will improve personalized and precise surgery in the near future. PMID:26864116

  3. Bean Common Mosaic Virus and Bean Common Mosaic Necrosis Virus: Relationships, Biology, and Prospects for Control.

    PubMed

    Worrall, Elizabeth A; Wamonje, Francis O; Mukeshimana, Gerardine; Harvey, Jagger J W; Carr, John P; Mitter, Neena

    2015-01-01

    The closely related potyviruses Bean common mosaic virus (BCMV) and Bean common mosaic necrosis virus (BCMNV) are major constraints on common bean (Phaseolus vulgaris) production. Crop losses caused by BCMV and BCMNV impact severely not only on commercial scale cultivation of this high-value crop but also on production by smallholder farmers in the developing world, where bean serves as a key source of dietary protein and mineral nutrition. In many parts of the world, progress has been made in combating BCMV through breeding bean varieties possessing the I gene, a dominant gene conferring resistance to most BCMV strains. However, in Africa, and in particular in Central and East Africa, BCMNV is endemic and this presents a serious problem for deployment of the I gene because this virus triggers systemic necrosis (black root disease) in plants possessing this resistance gene. Information on these two important viruses is scattered throughout the literature from 1917 onward, and although reviews on resistance to BCMV and BCMNV exist, there is currently no comprehensive review on the biology and taxonomy of BCMV and BCMNV. In this chapter, we discuss the current state of our knowledge of these two potyviruses including fundamental aspects of classification and phylogeny, molecular biology, host interactions, transmission through seed and by aphid vectors, geographic distribution, as well as current and future prospects for the control of these important viruses. PMID:26111585

  4. [Role of core decompression as treatment method for ischemic femur head necrosis].

    PubMed

    Hungerford, D S

    1990-08-01

    Nontraumatic ischemic necrosis of the femoral head remains a source of much controversy. The etiology is also controversial. Possibilities are: hypertrophy of intraosseous structures (lipocytes, hematopoietic elements), creating intraosseous hypertension; alcohol and steroids as toxic agents; circulating fat globules embolizing the microcirculation of the metaphysis. The disease appears most frequently in young adults, but no satisfactory nonoperative treatment modalities have been reported as yet. In 1971, Ficat and Arlet published their results on core decompression performed in 100 patients, with a follow-up of from 1 to 5 years. The results for those with stage I disease (n = 40) were good or excellent in 88% of the patients. The results for those with stage II disease (n = 16) were good or excellent in 69%. Based on current experience, the treatment is to be recommended for patients with pre-collapse stages 0, I and IIA of ischemic necrosis of the femoral head. For stage III disease, the procedure may reduce pain at night and at rest and can be considered in patients wishing to avoid total hip arthroplasty for a period of time. PMID:2216450

  5. Computational modeling of tuberculous meningitis reveals an important role for tumor necrosis factor-α

    PubMed Central

    El-Kebir, M.; van der Kuip, M.; van Furth, A.M.; Kirschner, D.E.

    2013-01-01

    Tuberculosis is a global health issue with annually about 1.5 million deaths and 2 billion infected people worldwide. Extra pulmonary tuberculosis comprises 13% of all cases of which tuberculous meningitis is the most severe. It has a high mortality and is often diagnosed once irreversible neurological damage has already occurred. Development of diagnostic and treatment strategies requires a thorough understanding of the pathogenesis of tuberculous meningitis. This disease is characterized by the formation of a cerebral granuloma, which is a collection of immune cells that attempt to immunologically restrain, and physically contain bacteria. The cytokine tumor necrosis factor-α is known for its important role in granuloma formation. Because traditional experimental animal studies exploring tuberculous meningitis are difficult and expensive, another approach is needed to begin to address this important and significant disease outcome. Here, we present an in silico model capturing the unique immunological environment of the brain that allows us to study the key mechanisms driving granuloma formation in time. Uncertainty and sensitivity analysis reveal a dose-dependent effect of tumor necrosis factor-α on bacterial load and immune cell numbers thereby influencing the onset of tuberculous meningitis. Insufficient levels result in bacterial overgrowth, whereas high levels lead to uncontrolled inflammation being detrimental to the host. These findings have important implications for the development of immuno-modulating treatment strategies for tuberculous meningitis. PMID:23542051

  6. Tumor necrosis factor and interleukin 1 as mediators of endotoxin-induced beneficial effects

    SciTech Connect

    Urbaschek, R.; Urbaschek, B.

    1987-09-01

    Bacterial lipopolysaccharides or endotoxins are known to induce tumor necrosis; enhanced nonspecific resistance to bacterial, viral, and parasitic infections and to radiation sickness; and tolerance to lethal doses of endotoxin. These beneficial effects are achieved by pretreatment with minute amounts of endotoxin. Recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) are among the mediators capable of invoking radioprotection or resistance to the consequences of cecal ligation and puncture. Both cytokines are potent inducers of serum colony-stimulating factor (CSF) in C3H/HeJ mice (low responders to endotoxin). The number of splenic granulocyte-macrophage precursors was found to increase 5 days after injection of TNF in these mice. Although with IL-1 no increase in the number of granulocyte-macrophage colonies occurred in culture in the presence of serum CSF, a marked stimulation was observed when TNF was added. This stimulation of myelopoiesis observed in vivo and in vitro may be related to the radioprotective effect of TNF. The data presented suggest that TNF and IL-1 released after injection of endotoxin participate in the mediation of endotoxin-induced enhancement of nonspecific resistance and stimulation of hematopoiesis. 76 references.

  7. Avascular necrosis after oral corticosteroids in otolaryngology: Case report and review of the literature

    PubMed Central

    Bassiouni, Ahmed; Psaltis, Alkis; Antisdel, Jastin; Brunworth, Joseph

    2016-01-01

    Objective: In this report, we present a rare case of avascular necrosis (AVN) in an otherwise healthy 42-year-old male patient treated with low dose oral corticosteroids for his bronchitis. A systematic review of the literature related to AVN and corticosteroids was performed. Case Report: Forty-two-year-old male with no underlying conditions predisposing him to AVN who had been treated four years before for chronic bronchitis with two courses of oral prednisone therapy presented with bilateral AVN of the hips. Methods: An OVID database search of the terms “low total dose,” “corticosteroids,” and “avascular necrosis” was performed. Two PubMed searches of various permutations of “low-dose,” “corticosteroids,” “avascular necrosis,” and “osteonecrosis” were also performed. Results were then narrowed to relevant articles. Results: Median total dose of oral corticosteroids in patients with AVN in reviewed articles was 981 mg, with lowest reported association at 105 mg. Median duration of therapy was 16 days with shortest course of six days. Conclusion: There is emerging data linking AVN with corticosteroid doses previously thought to be safe. After reviewing the relevant literature, it is our consensus to inform all patients regarding AVN before oral corticosteroid use. PMID:27103562

  8. Successful plasma exchange combined with rituximab therapy in aggressive APS-related cutaneous necrosis.

    PubMed

    Costa, Rubens; Fazal, Salman; Kaplan, Robert B; Spero, Joel; Costa, Ricardo

    2013-03-01

    Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis or recurrent fetal loss associated with the presence of antiphospholipid antibodies and/or a lupus anticoagulant. The skin appears to be an important target organ and many cases of APS may present with skin manifestations. These lesions may be manifold and may take the form of livedo reticularis, livedo racemosa, ulcerations, digital gangrene, subungeal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis, or primary anetoderma. We report a case of fulminant APS-related cutaneous necrosis. A 38-year-old Caucasian male with a past history of APS, multiple deep vein thrombi/pulmonary emboli, presented with necrotic lesions on his right upper and right lower extremities. Initially, baseline anticoagulation was increased without improvement. Subsequently, plasma exchange was initiated on a daily schedule. Furthermore, rituximab 1,000 mg IV was administered on days 1 and 15. After six consecutive daily sessions of plasma exchange, there was significant regression of the necrotic lesions. After a 22-day hospital stay, the patient was discharged to home on fondaparinux. The patient presented approximately 2 months later after missing follow-up appointments. At the time, his initial lesions looked remarkably improved.

  9. Endotoxin-induced liver necrosis and intravascular coagulation in rats enhanced by portacaval collateral circulation.

    PubMed Central

    Liehr, H; Grün, M; Thiel, H; Brunswig, D; Rasenack, U

    1975-01-01

    The effects of intravenously administered endotoxin on the hepatic and systemic circulation as well as on the coagulation system were evaluated in normal rats (n = 26), in rats with experimental portal hypertension (n = 15), and in rats with portacaval anastomosis (n = 22). Endotoxin (1-5 mg/kg) in the normal rat leads to a prompt increase of transaminase activity and to a hyperdynamic circulation with a consequent increase in the total hepatic blood flow. In a later phase (6 h postoperatively) the hepatic artery dilated with a consequent hepatic arterial hyperperfusion. The coagulation system was affected with signs of consumption coagulopathy. In the rats with portal hypertension and portacaval collaterals as well as in those with portacaval anastomosis, the endotoxin injection resulted in acute liver necrosis within 12 to 15 hours. The hepatic artery became overdilated with a cardiac output fraction of 25% (normal 5-5%). Blood extravasates and thrombi, rich in fibrin, were detected in the liver. It is suggested that this exaggeration of the endotoxin effect was due to an impaired clearance function of the reticuloendothelial system, probably as consequence of portacaval collateral circulation. It is concluded that endotoxins (1) damage the liver even in a normal organism; (2) are potent to induce acute liver necrosis, if the reticuloendothelial system is altered; (3) have to be taken into consideration as contribution to the pathogenesis of acute as well as chronic liver diseases. Images Fig. 3 Fig. 4 PMID:1150113

  10. Salivary Biomarkers Associated with Myocardial Necrosis: Results from an Alcohol Septal Ablation Model

    PubMed Central

    Foley, Joseph D.; Sneed, J. Darrell; Steinhubl, Steven R.; Kolasa, Justin R.; Ebersole, Jeffrey L.; Lin, Yushun; Kryscio, Richard J.; McDevitt, John T.; Campbell, Charles L.; Miller, Craig S.

    2013-01-01

    Objective To determine if salivary biomarkers demonstrate utility for identifying aspects of myocardial necrosis. Methods Twenty-one patients undergoing alcohol septal ablation (ASA) for treatment of hypertrophic cardiomyopathy provided serum and unstimulated whole saliva at baseline and incremental time points post-ASA. Samples were analyzed for seven biomarkers related to myocardial damage, inflammation and tissue remodeling using immunosorbent assays. Levels were compared to baseline and levels observed in 97 healthy controls. Results Biomarkers of myocardial damage and inflammation (i.e., troponin I, creatine kinase-MB, myoglobin, C-reactive protein) rose in serum 2 to 812-fold after ASA (p<0.01). Significant elevations of 2 to 3.5-fold were observed with C-reactive protein and troponin I in saliva (p<0.02). Significant correlations between levels in serum and saliva were observed for C-reactive protein, matrix metalloproteinase-9, and myeloperoxidase (p < 0.001). Conclusions Select salivary biomarkers reflect changes that occur during, and subsequent to, myocardial necrosis caused by ASA. PMID:23021916

  11. Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

    NASA Technical Reports Server (NTRS)

    Pizza, F. X.; Hernandez, I. J.; Tidball, J. G.

    1998-01-01

    The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1+ and ED2+ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1+ and ED2+ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with water-treated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.

  12. Major histocompatibility complex loci are associated with susceptibility of Atlantic salmon to infectious hematopoietic necrosis virus

    USGS Publications Warehouse

    Miller, Kristina M.; Winton, James R.; Schulze, Angela D.; Purcell, Maureen K.; Ming, Tobi J.

    2004-01-01

    Infectious hematopoietic necrosis virus (IHNV) is one of the most significant viral pathogens of salmonids and is a leading cause of death among cultured juvenile fish. Although several vaccine strategies have been developed, some of which are highly protective, the delivery systems are still too costly for general use by the aquaculture industry. More cost effective methods could come from the identification of genes associated with IHNV resistance for use in selective breeding. Further, identification of susceptibility genes may lead to an improved understanding of viral pathogenesis and may therefore aid in the development of preventive and therapeutic measures. Genes of the major histocompatibility complex (MHC), involved in the primary recognition of foreign pathogens in the acquired immune response, are associated with resistance to a variety of diseases in vertebrate organisms. We conducted a preliminary analysis of MHC disease association in which an aquaculture strain of Atlantic salmon was challenged with IHNV at three different doses and individual fish were genotyped at three MHC loci using denaturing gradient gel electrophoresis (PCR-DGGE), followed by sequencing of all differentiated alleles. Nine to fourteen alleles per exon-locus were resolved, and alleles potentially associated with resistance or susceptibility were identified. One allele (Sasa-B-04) from a potentially non-classical class I locus was highly associated with resistance to infectious hematopoietic necrosis (p < 0.01). This information can be used to design crosses of specific haplotypes for family analysis of disease associations.

  13. RhoA GTPase controls cytokinesis and programmed necrosis of hematopoietic progenitors

    PubMed Central

    Zhou, Xuan; Florian, Maria Carolina; Arumugam, Paritha; Chen, Xiaoyi; Cancelas, Jose A.; Lang, Richard; Malik, Punam; Geiger, Hartmut

    2013-01-01

    Hematopoietic progenitor cells (HPCs) are central to hematopoiesis as they provide large numbers of lineage-defined blood cells necessary to sustain blood homeostasis. They are one of the most actively cycling somatic cells, and their precise control is critical for hematopoietic homeostasis. The small GTPase RhoA is an intracellular molecular switch that integrates cytokine, chemokine, and adhesion signals to coordinate multiple context-dependent cellular processes. By using a RhoA conditional knockout mouse model, we show that RhoA deficiency causes a multilineage hematopoietic failure that is associated with defective multipotent HPCs. Interestingly, RhoA−/− hematopoietic stem cells retained long-term engraftment potential but failed to produce multipotent HPCs and lineage-defined blood cells. This multilineage hematopoietic failure was rescued by reconstituting wild-type RhoA into the RhoA−/− Lin−Sca-1+c-Kit+ compartment. Mechanistically, RhoA regulates actomyosin signaling, cytokinesis, and programmed necrosis of the HPCs, and loss of RhoA results in a cytokinesis failure of HPCs manifested by an accumulation of multinucleated cells caused by failed abscission of the cleavage furrow after telophase. Concomitantly, the HPCs show a drastically increased death associated with increased TNF–RIP-mediated necrosis. These results show that RhoA is a critical and specific regulator of multipotent HPCs during cytokinesis and thus essential for multilineage hematopoiesis. PMID:24101377

  14. Production of interferon and tumour necrosis factor by cloned human natural cytotoxic lymphocytes and T cells.

    PubMed

    Christmas, S E; Meager, A; Moore, M

    1987-08-01

    Cell lines and clones, derived from natural killer (NK) cell-enriched (B73.1+) peripheral blood lymphocytes (PBL) from several human donors, that expressed distinct surface phenotypes and were cytolytically active against K562 target cells were tested for their capacity to produce interferon (IFN) and tumour necrosis factor (TNF), IFN and TNF were measured firstly in biological assays and secondly in specific immunoassays for alpha-IFN, gamma-IFN and tumour necrosis factor (TNF alpha). It was found that the majority of NK-derived lines and clones were highly cytotoxic towards K562, but generally produced relatively low or undetectable levels of gamma-IFN and TNF alpha following stimulation with phytohaemagglutinin. No alpha-IFN was detected in supernatants from these cells. In comparison, cell lines and clones, derived from T lymphocyte (B73.1-) enriched PBL from the same donors were poorly cytotoxic towards K562, but generally produced higher levels of gamma-IFN and TNF than NK-derived cells. Thus, neither gamma-IFN nor TNF production were shown to correlate well with the capacity of NK-derived or T cell clones to effect cytotoxic action towards K562 in vitro. These results suggest that the co-production of gamma-IFN and TNF is not indicative of cytotoxic potential.

  15. Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation.

    PubMed

    Ou, Sai-Hong Ignatius; Weitz, Michael; Jalas, John R; Kelly, Daniel F; Wong, Vanessa; Azada, Michele C; Quines, Oliver; Klempner, Samuel J

    2016-06-01

    Alectinib is a second generation ALK inhibitor that has significant clinical activity in central nervous system (CNS) metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Pseudoprogression (PsP) due to radiation necrosis during alecitnib treatment of central nervous system (CNS) metastases from ALK-rearranged NSCLC as been reported. Hence, distinguishing radiation-related PsP from alectinib-induced radiographic changes is important to avoid erroneous early trial discontinuation and abandonment of an effective treatment. However, it remains difficult to assess casuality of radiation necrosis is related to recent direct radiation or induced by alectinib treatment or both. It is also unknown how long from previous radiation can alectinib still induce radiation necrosis. Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib. His most recent radiation to his CNS metastases was 7 years prior to the start of alectinib. This case illustrates that in the setting of pror CNS radiation, given the significant clinical activity of alectinib in CNS metastases in ALK-positive NSCLC patients the risk of CNS radiation necrosis remains long after previous radiation to the CNS metastases has been completed and can occur after durable response of treatment. PMID:27133743

  16. Factors responsible for the development of avascular necrosis secondary to the treatment of congenital dislocation of the hip.

    PubMed

    Burgos-Flores, J; Ocete-Guzman, G; Gonzalez-Herranz, P; Hevia-Sierra, E; Amaya-Alarcon, S

    1993-11-01

    We present 104 cases of unilateral congenital dislocation of the hip treated with the same regime between 1977 and 1988. The patients had an average age of 12 months (range 4-24). The average age at follow-up was 6 years (range 3-13). The incidence of avascular necrosis was 37%. Avascular necrosis presented most frequently in babies of 7 months at the start of treatment, in Tonnis type IV when an adductor tenotomy was not performed, and after open reductions. The most influential factor was the absence of the femoral head descent at the end of the period of traction. The "effective" prereduction traction and the performance of an adductor tenotomy when necessary were the principle factors in avoiding avascular necrosis.

  17. Multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2

    PubMed Central

    Oz, Helieh S

    2016-01-01

    AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues. METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with Sirius Red staining. RESULTS: Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls (P < 0.0001). These pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 ± 0.2 (severe) in DBTC-treated animals vs score 0 (normal) in sham-treated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with Sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma, infiltration of

  18. The effects of treatment the avascular necrosis of the femoral head with extracorporeal focused shockwave therapy.

    PubMed

    Kusz, Damian; Franek, Andrzej; Wilk, Robert; Dolibog, Paweł; Błaszczak, Edward; Wojciechowski, Piotr; Król, Piotr; Dolibog, Patrycja; Kusz, Błażej

    2012-01-01

    Background.Avascular necrosis of the femoral head continues to represent a major challenge for the orthopaedist and trauma surgeon. A fully effective method of treatment is yet to be introduced. After femoral head collapse, only total hip replacement can help the patient. Our study aims to assess the effects of treatment of avascular necrosis of the femoral head with extra corporeal focused shockwave therapy.Material and methods. A prospective study was carried out in patients with avascular necrosis of the femoral head, ARCO stage I-III, diagnosed by MRI imaging. Shock waves are applied under x-ray guidance. Four points are marked on the skin above the lesion. Each spot receives a dose of 1500 pulses at an energy flux density of 0.4 mJ/mm2 and a frequency of 4 Hz. Each patient undergoes 5 therapy sessions. A posturometric and stabilometric assessment is carried out before and after the therapy. Other examinations include a tensometric evaluation of the strength of the treated limb, and an assessment of pain intensity (VAS scale)and hip function (Harris hip score). Follow-up visits are scheduled at 6 weeks and 3, 6 and 12 months post-treatment.Results. Nine patients were treated with shockwave therapy at the Department of Orthopaedics and Musculoskeletal Traumatology, Medical Faculty, Medical University of Silesia, between 5 May 2011 and 1 June 2012. The patients demonstrated pain reduction and improved mobility of the treated joint (VAS score decreasing from 6.75 +/- 0.71 to 2.5 +/- 1.7; Harris hip score increasing from 55.21 +/- 15.45 to 89.21 +/- 8.26). Tensometric platform testing carried out after the treatment revealed a statistically significant difference between mean velocity of the centre of pressure (CoP) movement when walking with eyes open and closed (p<0.05) and mean CoP movement along the x (walking with eyes closed) and y (free standing with eyes closed) axes.Conclusions. 1. Extracorporeal focused shockwave therapy resulted in considerable

  19. Trophoblastic cell lines generated from tumour necrosis factor receptor-deficient mice reveal specific functions for the two tumour necrosis factor receptors.

    PubMed

    Rasmussen, C A; Pace, J L; Banerjee, S; Phillips, T A; Hunt, J S

    1999-01-01

    In mice and humans, expression of the tumour necrosis factor receptor-1 (TNF-R1) gene in placental trophoblast cells is constitutive whereas expression of the TNF-R2 gene is developmentally programmed. In order to study the individual functions of TNF-R1 and -R2 in this lineage, cell lines were generated from placental explants of homozygous matings of gestation day 10 outbred mice (Swiss-Webster), TNF-R1-deficient (TNF-R1-/-) and TNF-R2-/- transgenic mice as well as the background strain for the TNF-R2-/- mice (WT, C57BL/6x129). All of the cells exhibited trophoblast markers; they contained cytokeratin intermediate filaments, expressed alkaline phosphatase activity and displayed transferrin receptors, but were negative for vimentin filaments and the macrophage marker, F4/80. Analysis of DNA by polymerase chain reaction demonstrated the expected TNF-R genotype in each line. In experiments testing the effects of recombinant mouse TNF-alpha (rmTNF-alpha) on viability and proliferation of the cell lines, rmTNF-alpha modestly but dose-dependently inhibited the growth of WT and TNF-R2-/- cells while having no effect on TNF-R1-/- cells. Actinomycin D-treated WT and, to a lesser extent, TNF-R2-/- cells, were more sensitive to growth inhibition than untreated cells whereas TNF-R1-/- cell responses remained unchanged. These data indicated that rmTNF-alpha inhibits growth of trophoblastic cells through TNF-R1 and that newly synthesized protein(s) provide partial protection against toxicity. In contrast to the receptor species-specific effects on cell growth exerted by rmTNF-alpha, both TNF-R mediated inhibition of alkaline phosphatase activity. Collectively, the observations support the postulate that receptor expression is the key factor which determines the nature and extent of TNF-alpha effects on trophoblast cell growth and function.

  20. Improvement of solubility and targetability of radioiodinated hypericin by using sodium cholate based solvent in rat models of necrosis.

    PubMed

    Ji, Yun; Zhan, Ying; Jiang, Cuihua; Jiang, Xiao; Gao, Meng; Liu, Wei; Li, Yue; Wang, Junhu; Wang, Qingqing; Cona, Marlein Miranda; Yao, Nan; Wang, Xiaoning; Fang, Zhijun; Yin, Zhiqi; Zhang, Jian; Sun, Ziping; Ni, Yicheng

    2014-05-01

    Hypericin (Hyp) is newly recognized as a necrosis avid agent, but its poor solubility imposes a great hindrance in clinical application. The aim of this paper was to explore sodium cholate (NaCh) as a potential solvent for Hyp and assess the targetability of (131)I-Hyp in rat necrosis models. Hyp solubility in NaCh solutions was evaluated by equilibrium solubility measurement. Biodistribution of (131)I-Hyp in NaCh solutions and mixed organic solvents was investigated in rat models of liver and muscle necrosis examined with MRI and SPECT/CT in vivo. In addition, pharmacokinetics of (131)I-Hyp in NaCh solutions was studied in healthy rats. Results showed NaCh could improve Hyp solubility and (131)I-Hyp incubated in NaCh solutions/rat plasma was stable up to 120 h. On SPECT/CT images at 24 h post injection, liver infarction location appeared as hot spots. Liver necrosis-to-liver ratios were 12.2, 10.0, 9.6 and 8.2 in 60, 15, 2 mmol/L of NaCh solutions and organic solvents, and muscle necrosis-to-liver ratios were 11.1, 10.1, 7.7 and 7.4, respectively. Pharmacokinetics study revealed t(1/2)z (11.93, 8.96 h, p > 0.05) and AUC (0-∞) (421.21, 553.34 MBq/L h, p < 0.05) of (131)I-Hyp in 2, 60 mmol/L of NaCh solutions, respectively. In conclusion, NaCh was an effective cosolvent, and the necrosis avidity of NaCh-dissolved (131)I-Hyp/Hyp was demonstrated.

  1. Correlation between liver cell necrosis and circulating alanine aminotransferase after ischaemia/reperfusion injuries in the rat liver.

    PubMed

    Knudsen, Anders R; Andersen, Kasper J; Hamilton-Dutoit, Stephen; Nyengaard, Jens R; Mortensen, Frank V

    2016-04-01

    Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design-unbiased stereological methods. Forty-seven male Wistar rats were subjected to 1 h of partial liver ischaemia, followed by either 4 or 24 h of reperfusion. Within each group, one-third of animals were subjected to ischaemic preconditioning and one-third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4 h of reperfusion; however, at this time-point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P = 0.001). After 24 h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R = 0.836 (P = 0.000). Furthermore, alkaline phosphatase (R = 0.806) and α-2-macroglobulin (R = 0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24 h of reperfusion. Similarly, increased levels of alkaline phosphatase and α-2-macroglobulin are correlated to the volume of liver necrosis. PMID:27292534

  2. Tumor necrosis is associated with increased alphavbeta3 integrin expression and poor prognosis in nodular cutaneous melanomas

    PubMed Central

    Bachmann, Ingeborg M; Ladstein, Rita G; Straume, Oddbjørn; Naumov, George N; Akslen, Lars A

    2008-01-01

    Background Tumor necrosis and apoptotic activity are considered important in cancer progression, but these features have not been much studied in melanomas. Our hypothesis was that rapid growth in cutaneous melanomas of the vertical growth phase might lead to tissue hypoxia, alterations in apoptotic activity and tumor necrosis. We proposed that these tumor characteristics might be associated with changes in expression of cell adhesion proteins leading to increased invasive capacity and reduced patient survival. Methods A well characterized series of nodular melanoma (originally 202 cases) and other benign and malignant melanocytic tumors (109 cases) were examined for the presence of necrosis, apoptotic activity (TUNEL assay), immunohistochemical expression of hypoxia markers (HIF-1 α, CAIX, TNF-α, Apaf-1) and cell adhesion proteins (αvβ3 integrin, CD44/HCAM and osteopontin). We hypothesized that tumor hypoxia and necrosis might be associated with increased invasiveness in melanoma through alterations of tumor cell adhesion proteins. Results Necrosis was present in 29% of nodular melanomas and was associated with increased tumor thickness, tumor ulceration, vascular invasion, higher tumor proliferation and apoptotic index, increased expression of αvβ3 integrin and poor patient outcome by multivariate analysis. Tumor cell apoptosis did also correlate with reduced patient survival. Expression of TNF-α and Apaf-1 was significantly associated with tumor thickness, and osteopontin expression correlated with increased tumor cell proliferation (Ki-67). Conclusion Tumor necrosis and apoptotic activity are important features of melanoma progression and prognosis, at least partly through alterations in cell adhesion molecules such as increased αvβ3 integrin expression, revealing potentially important targets for new therapeutic approaches to be further explored. PMID:19061491

  3. Severe Radiation Necrosis Successfully Treated With Bevacizumab in an Infant with Low-Grade Glioma and Tumor-Associated Intractable Trigeminal Neuralgia.

    PubMed

    Pillay Smiley, Natasha; Alden, Tord; Hartsell, William; Fangusaro, Jason

    2016-09-01

    We present a unique case of radiation necrosis in a child with brain stem low-grade glioma (LGG) presenting with trigeminal neuralgia. Despite extensive therapies, severe pain persisted. She received proton beam radiation with significant improvement. However, she developed radiation necrosis and hydrocephalus. Despite surgical correction of hydrocephalus, the patient remained critically ill. She was treated with dexamethasone and bevacizumab with rapid clinical improvement. Subsequent MRIs revealed almost complete resolution of the necrosis. This case illustrates the successful treatment of trigeminal neuralgia with radiation and a rare case of radiation necrosis in an LGG successfully treated with bevacizumab and dexamethasone. PMID:27187113

  4. Effect of the anti-oestrogen tamoxifen on the development of renal cortical necrosis induced by oestrone + vasopressin administration in rats.

    PubMed Central

    Kocsis, J.; Karácsony, G.; Karcsú, S.; László, F. A.

    1988-01-01

    Bilateral renal cortical necrosis was observed after vasopressin administration in rats pretreated with oestrone acetate. Histochemical (succinic dehydrogenase, trichrome, periodic acid Schiff) and electronmicroscopic methods were used to examine how the anti-oestrogen, Tamoxifen, influences the development of this renal cortical necrosis. The experiments revealed that in most rats vasopressin did not induce renal tubular necrosis if the anti-oestrogen was administered simultaneously, even during oestrogen pretreatment. The results suggest that oestrogen receptors in the kidney are involved in the induction of renal cortical necrosis by vasopressin. Images Fig. 5 Fig. 5 Fig. 3 Fig. 4 Fig. 1 Fig. 2 PMID:3377960

  5. A Case of Intestinal Necrosis after Bilateral Internal Iliac Artery-Preserving Endovascular Repair for Abdominal Aortic Aneurysm

    PubMed Central

    Sato, Masataka; Imai, Akito; Watanabe, Yasunori

    2016-01-01

    A 79-year-old man underwent endovascular repair for abdominal aortic aneurysm (AAA), and both internal iliac arteries (IIAs) were preserved. Postoperatively, loss of appetite developed. On the fifth day, computerized tomography (CT) showed inferior mesenteric artery thrombus formation, necrosis of the descending colon and rectum, and generalized peritonitis. The endovascular devices had not migrated. A colonic resection was performed. Histological analysis confirmed intestinal necrosis associated with mesenteric thrombus. The colon can become necrotic even if both IIAs are patent. Ischemic changes in the colon should be detected if it occurs and subsequent laparotomy should be done if it is necessary.

  6. Mitophagy switches cell death from apoptosis to necrosis in NSCLC cells treated with oncolytic measles virus.

    PubMed

    Xia, Mao; Meng, Gang; Jiang, Aiqin; Chen, Aiping; Dahlhaus, Meike; Gonzalez, Patrick; Beltinger, Christian; Wei, Jiwu

    2014-06-15

    Although apoptotic phenomena have been observed in malignant cells infected by measles virus vaccine strain Edmonston B (MV-Edm), the precise oncolytic mechanisms are poorly defined. In this study we found that MV-Edm induced autophagy and sequestosome 1-mediated mitophagy leading to decreased cytochrome c release, which blocked the pro-apoptotic cascade in non-small cell lung cancer cells (NSCLCs). The decrease of apoptosis by mitophagy favored viral replication. Persistent viral replication sustained by autophagy ultimately resulted in necrotic cell death due to ATP depletion. Importantly, when autophagy was impaired in NSCLCs MV-Edm-induced cell death was significantly abrogated despite of increased apoptosis. Taken together, our results define a novel oncolytic mechanism by which mitophagy switches cell death from apoptosis to more efficient necrosis in NSCLCs following MV-Edm infection. This provides a foundation for future improvement of oncolytic virotherapy or antiviral therapy.

  7. The Possible Role of Tumor Necrosis Factor-α in Diabetic Polyneuropathy

    PubMed Central

    Yagihashi, Soroku; Toyota, Takayoshi

    2003-01-01

    In this review, the authors provide evidences that imply the role of tumor necrosis factor-α (TNF-α) in the pathogenesis of diabetic complications, especially diabetic polyneuropathy. Under chronic hyperglycemia, endogenous TNF-α production is accelerated in microvascular and neural tissues, which may undergo an increased microvascular permeability, hypercoagulability, and nerve damage, thus initiating and promoting the development of characteristic lesions of diabetic microangiopathy and polyneuropathy. Enhanced TNF-α production may also promote atherosclerosis due to increased insulin resistance and the expression of adhesion molecules. Clinical application of specific agents that suppress production and/or activity of TNF-α may inhibit the development and exacerbation of chronic diabetic complications. PMID:14630568

  8. Viral fitness does not correlate with three genotype displacement events involving infectious hematopoietic necrosis virus

    USGS Publications Warehouse

    Kell, Alison M.; Wargo, Andrew R.; Kurath, Gael

    2014-01-01

    Viral genotype displacement events are characterized by the replacement of a previously dominant virus genotype by a novel genotype of the same virus species in a given geographic region. We examine here the fitness of three pairs of infectious hematopoietic necrosis virus (IHNV) genotypes involved in three major genotype displacement events in Washington state over the last 30 years to determine whether increased virus fitness correlates with displacement. Fitness was assessed using in vivo assays to measure viral replication in single infection, simultaneous co-infection, and sequential superinfection in the natural host, steelhead trout. In addition, virion stability of each genotype was measured in freshwater and seawater environments at various temperatures. By these methods, we found no correlation between increased viral fitness and displacement in the field. These results suggest that other pressures likely exist in the field with important consequences for IHNV evolution.

  9. Herpes Zoster Induced Alveolar Bone Necrosis in Immunocompromised Patients; Two Case Reports

    PubMed Central

    Gholami, Mahdi; Shahakbari, Reza; Abdolahpour, Somayeh; Hatami, Masoud; Roshanmir, Azam

    2016-01-01

    Introduction: Herpes zoster Infection (HZI) is a viral disease with painful skin rashes and blisters in a limited area on one side of the body, often in a strip. Osteonecrosis with spontaneous exfoliation of teeth in association with HZI of the mandibular nerve is a rare phenomenon. In this report, such an unusual complication of HZI is presented. Case Report: The clinical course of a 53-year-old woman and a 54-year-old man with HZI associated with alveolar bone necrosis and tooth exfoliation were reviewed in order to develop a patient profile for this rare combination of physical findings. Conclusion: In immunocompromised patients, the clinicians should consider HZI as a possible cause of tooth mobility, exfoliation, and alveolar osteonecrosis, which needs early intervention to prevent secondary complications. PMID:27738615

  10. An approach to avascular necrosis by Saghṛta kṣīrabasti

    PubMed Central

    Chaganti, Sreelaksmi; Sanipeti, Rajashekhar V.; Joshi, Suma S. S.

    2013-01-01

    A 62-year-old, male patient radiologically diagnosed as a case of avascular necrosis of femur head with grade 4, presented the following chief complaints. Pain in the left hip joint radiating to thigh (anterior part), of grade ‘9’ on “visual analog scale (VAS)” associated with swelling in bilateral feet and decreased range of movements in the hip joint. This presentation was correlated with Asthi-majjagata vāta (musculo-skeletal disorder) and treated accordingly. Initially, patient had been administered dīpana and pācana followed by nityavirecana (therapeutic purgation). Further Saghrita kṣīrabasti (medicated enema prepared with milk and ghee) was administered in kalābasti schedule (16 in number). This resulted with relief of pain to grade “3” on “VAS” and complete resolution of pedal edema and improvement in range of movement of hip joint. PMID:25161330

  11. The role of tumor necrosis factor receptor superfamily members in mammalian brain development, function and homeostasis

    PubMed Central

    Twohig, Jason P.; Cuff, Simone M.; Yong, Audrey A.; Wang, Eddie C.Y.

    2012-01-01

    Tumor necrosis factor receptor superfamily (TNFRSF) members were initially identified as immunological mediators, and are still commonly perceived as immunological molecules. However, our understanding of the diversity of TNFRSF members’ roles in mammalian physiology has grown significantly since the first discovery of TNFRp55 (TNFRSF1) in 1975. In particular, the last decade has provided evidence for important roles in brain development, function and the emergent field of neuronal homeostasis. Recent evidence suggests that TNFRSF members are expressed in an overlapping regulated pattern during neuronal development, participating in the regulation of neuronal expansion, growth, differentiation and regional pattern development. This review examines evidence for non-immunological roles of TNFRSF members in brain development, function and maintenance under normal physiological conditions. In addition, several aspects of brain function during inflammation will also be described, when illuminating and relevant to the non-immunological role of TNFRSF members. Finally, key questions in the field will be outlined. PMID:21861782

  12. Viral fitness does not correlate with three genotype displacement events involving infectious hematopoietic necrosis virus.

    PubMed

    Kell, Alison M; Wargo, Andrew R; Kurath, Gael

    2014-09-01

    Viral genotype displacement events are characterized by the replacement of a previously dominant virus genotype by a novel genotype of the same virus species in a given geographic region. We examine here the fitness of three pairs of infectious hematopoietic necrosis virus (IHNV) genotypes involved in three major genotype displacement events in Washington state over the last 30 years to determine whether increased virus fitness correlates with displacement. Fitness was assessed using in vivo assays to measure viral replication in single infection, simultaneous co-infection, and sequential superinfection in the natural host, steelhead trout. In addition, virion stability of each genotype was measured in freshwater and seawater environments at various temperatures. By these methods, we found no correlation between increased viral fitness and displacement in the field. These results suggest that other pressures likely exist in the field with important consequences for IHNV evolution. PMID:25068402

  13. Production of tumor necrosis factor alpha, interleukin-1 alpha, and interleukin-6 during murine coccidioidomycosis.

    PubMed Central

    Cox, R A; Magee, D M

    1995-01-01

    The proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and interleukin-6 (IL-6) were induced in mice infected with Coccidioides immitis. Analyses of the cytokine profiles of two inbred mouse strains which differ in their susceptibility to pulmonary challenge with C. immitis revealed higher levels of IL-6 in lungs from DBA/2 mice (resistant strain) than in those from BALB/c mice (susceptible strain) beginning at day 6 and continuing through day 15 postinfection. Spleen cells from both mouse strains secreted TNF-alpha, IL-1 alpha, and IL-6 in vitro in response to stimulation with killed spherules but differed in that spleen cells from the resistant strain produced increased levels of these cytokines earlier after pulmonary challenge and at increased levels throughout the course of the disease. PMID:7558338

  14. Tumor Necrosis Factor-α -and Interleukin-1-Induced Cellular Responses: Coupling Proteomic and Genomic Information

    PubMed Central

    Ott, Lee W.; Resing, Katheryn A.; Sizemore, Alecia W.; Heyen, Joshua W.; Cocklin, Ross R.; Pedrick, Nathan M.; Woods, H. Cary; Chen, Jake Y.; Goebl, Mark G.; Witzmann, Frank A.; Harrington, Maureen A.

    2010-01-01

    The pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNFα) and Interleukin-1 (IL-1) mediate the innate immune response. Dysregulation of the innate immune response contributes to the pathogenesis of cancer, arthritis, and congestive heart failure. TNFα- and IL-1-induced changes in gene expression are mediated by similar transcription factors; however, TNFα and IL-1 receptor knock-out mice differ in their sensitivities to a known initiator (lipopolysaccharide, LPS) of the innate immune response. The contrasting responses to LPS indicate that TNFα and IL-1 regulate different processes. A large-scale proteomic analysis of TNFα- and IL-1-induced responses was undertaken to identify processes uniquely regulated by TNFα and IL-1. When combined with genomic studies, our results indicate that TNFα, but not IL-1, mediates cell cycle arrest. PMID:17503796

  15. Theiler's murine encephalomyelitis virus induces tumour necrosis factor-alpha in murine astrocyte cell cultures.

    PubMed Central

    Sierra, A; Rubio, N

    1993-01-01

    Cytokines have been postulated to exert an important modulatory and recruiting role in demyelination induced by Theiler's murine encephalomyelitis virus (TMEV) in SJL/J mice. Using a cytolytic bioassay and ELISA, we have detected and quantified a cytokine, tumour necrosis factor-alpha (TNF-alpha), in supernatants from astrocyte cultures infected in vitro with TMEV. TNF was detected only after TMEV-specific infection of astrocyte cultures (approximately 200-400 U/ml). In vitro TNF synthesis appeared in a dose- and time-dependent manner and was produced by both SJL/J (a strain susceptible to TMEV-induced demyelination) and BALB/c (a resistant strain) astrocytes. The precise nature of TNF activity was further assessed by fast protein liquid chromatography (FPLC) and antibody neutralization. These results indicate an active role for astrocytes as accessory immune cells in our experimental model for multiple sclerosis. PMID:8478023

  16. Tumor necrosis factor antagonists in the treatment of multicentric reticulohistiocytosis: Current clinical evidence

    PubMed Central

    ZHAO, HONGJUN; WU, CHUNMEI; WU, MENGYUN; ZHOU, YAOU; ZHU, HONGLIN; LI, YISHA; YOU, YUNHUI; LUO, HUI; WANG, LIJING; ZUO, XIAOXIA

    2016-01-01

    Multicentric reticulohistiocytosis (MRH) is a rare and debilitating systemic disorder characterized by cutaneous nodules and destructive polyarthritis. Due to its unknown etiology, the treatment of MRH varies with different rates of success, which causes treatment options to be rather independent and empirical. In the present study, a case of a 48-year-old woman with a 12-month history of polyarthralgia and skin nodules was reported. Biopsy samples, which were obtained from her skin eruption exhibited dermal infiltration with histiocytes and multinucleated giant cells. Immunohistochemical staining indicated positivity for CD68. The patient was diagnosed with MRH and treated with a combination therapy of infliximab, prednisolone and methotrexate. Her symptoms improved markedly within 2 weeks. Following the results of this case study, a systematic review of 17 cases of MRH treated with tumor necrosis factor (TNF) antagonists was performed, and the efficacy of anti-TNF treatment in MRH was analyzed. PMID:27175854

  17. Italian experience on use of E.S.W. therapy for avascular necrosis of femoral head.

    PubMed

    Russo, Sergio; Sadile, Francesco; Esposito, Roberto; Mosillo, Giuseppe; Aitanti, Emanuele; Busco, Gennaro; Wang, Ching-Jen

    2015-12-01

    Osteonecrosis (avascular necrosis) of the femoral head is a clinical disease due to a severe bone vascular alteration associated with intense pain and loss of joint function, with an incidence of 0.1% and unknown aetiology. Many classifications exist to describe it and in the final stages the patient will need a total hip arthroplasty. In the early stages, ESWT has given excellent responses.
 The Neapolitan school studied more than 600 patients who had very good results in I and II stages of Ficat and Arlet Classification, with an improve of outcomes in VAS and HSS scores. Moreover it has shown a complete restoration of the signal intensity of the femoral head in MRI.

  18. Endotoxin and tumor necrosis factor-alpha-induced interleukin-8 release in humans.

    PubMed

    van Deventer, S J; Hart, M; van der Poll, T; Hack, C E; Aarden, L A

    1993-02-01

    Neutrophil recruitment and activation are thought to play an important role in tissue damage observed in septicemia. Interleukin-8 (IL-8) is a small cytokine with important neutrophil-activating and chemoattractant properties. IL-8 release was studied after injection of human volunteers with low doses of either endotoxin (2 ng/kg of body weight) or tumor necrosis factor-alpha (TNF alpha) (50 micrograms/m2). After TNF-alpha injection, IL-8 appeared at 30 min, whereas increased levels were first observed after 90 min in endotoxin-challenged volunteers. Peak levels were measured at 120 min after both endotoxin (192 +/- 193 ng/L) and TNF alpha (500 +/- 236 ng/L) injection. These data indicate that IL-8 is released in humans after injection of endotoxin and TNF alpha and suggest that endotoxin-induced IL-8 release is mediated by TNF alpha.

  19. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients. PMID:15255240

  20. Aseptic tissue necrosis and chronic inflammation after irrigation of penetrating hand wounds using Octenisept®.

    PubMed

    Franz, T; Vögelin, E

    2012-01-01

    Penetrating hand wounds are common and these are managed by thorough debridement. However, stab wounds without evidence of divided structures are often treated with irrigation using antiseptic substances, antibiotic therapy, and immobilization. Octenisept® (Schülke & Mayr Ltd) is a widely used antiseptic agent for disinfection of acute or chronic wounds. It has a broad spectrum of antiseptic efficacy and has become an antiseptic of first choice in many hospitals. Within a few months, four patients presented to us with chronic inflammation and severe tissue necrosis after irrigation of penetrating hand wounds with Octenisept®. Repeated surgery and debridement was required in all patients. Wound healing was prolonged and patients had persisting oedema. Penetrating hand wounds must not be irrigated with Octenisept®.

  1. Association of progressive outer retinal necrosis and varicella zoster encephalitis in a patient with AIDS.

    PubMed Central

    van den Horn, G J; Meenken, C; Troost, D

    1996-01-01

    BACKGROUND: A patient with AIDS who developed the clinical picture of bilateral progressive outer retinal necrosis (PORN) in combination with varicella zoster encephalitis is described. The picture developed more than 2 years after an episode of ophthalmic zoster infection, and following intermittent exposure to oral acyclovir because of recurrent episodes of cutaneous herpes simplex infection. METHODS: Aqueous humour, obtained by paracentesis of the anterior chamber, was analysed using immunofluorescence and polymerase chain reaction (PCR). Postmortem analysis of eye and brain tissue was performed by using conventional techniques and in situ hybridisation. RESULTS: While conventional techniques all failed to detect a causative agent, analysis of the aqueous humour using PCR, and histological examination of necropsy specimens from eyes and brain using in situ hybridisation were conclusive for the diagnosis varicella zoster virus (VZV) infection. CONCLUSION: This case documents the presumed association of PORN and VZV encephalitis in a severely immunocompromised AIDS patient. Images PMID:8976726

  2. Trapped without a diagnosis: Tumour necrosis factor receptor-associated periodic syndrome (TRAPS).

    PubMed

    Kirresh, Ali; Everitt, Alex; Kon, Onn Min; DasGupta, Ranan; Pickering, Matthew C; Lachmann, Helen J

    2016-08-01

    Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant condition caused by mutations in the TNFRSF1A gene. It is characterised by recurrent episodes of myalgia, followed by prolonged fever, migratory rashes, headache, serositis, arthralgia, abdominal pain and periorbital oedema. We describe a 49-year-old man with a self-limiting episode of paraparesis who reported recurrent bouts of abdominal symptoms and headaches since childhood. He had a persistent inflammatory response with night sweats and weight loss. We diagnosed TRAPS 2 years after having identified a TNFRSF1A gene mutation. His symptoms and inflammatory response resolved dramatically with the interleukin-1 receptor antagonist anakinra. PMID:26965498

  3. Rapid simultaneous detection and quantitation of infectious pancreatic necrosis virus (IPNV).

    PubMed

    Espinoza, Juan Carlos; Kuznar, Juan

    2002-08-01

    Infectious pancreatic necrosis virus (IPNV) is a pathogen of great concern in the salmon industry as well as in the environment. Taking advantage of the early immunofluorescent visualization of viral proteins in infected cells, a titration method was developed. At 16 h p.i., fluorescent foci were visualized with a monoclonal antibody against VP3-structural protein of the virus. The counting of each fluorescent cell allows the quantitation of infection foci; titres expressed in fluorescent foci/ml were equivalent to plaque forming units (PFU)/ml. With slight modifications, the same method used to detect the virus in field samples, can be applied to estimate virus contents. Some of the samples used during the assays were obtained from routine screening procedures. The titres recorded from positive samples correlated well with the clinical condition of the fish. With this method, rapid diagnosis and quantitation may simultaneously be performed with the same tissue extract.

  4. Allorecognition Triggers Autophagy and Subsequent Necrosis in the Cnidarian Hydractinia symbiolongicarpus

    PubMed Central

    Buss, Leo W.; Anderson, Christopher; Westerman, Erica; Kritzberger, Chad; Poudyal, Monita; Moreno, Maria A.; Lakkis, Fadi G.

    2012-01-01

    Transitory fusion is an allorecognition phenotype displayed by the colonial hydroid Hydractinia symbiolongicarpus when interacting colonies share some, but not all, loci within the allorecognition gene complex (ARC). The phenotype is characterized by an initial fusion followed by subsequent cell death resulting in separation of the two incompatible colonies. We here characterize this cell death process using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and continuous in vivo digital microscopy. These techniques reveal widespread autophagy and subsequent necrosis in both colony and grafted polyp assays. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays and ultrastructural observations revealed no evidence of apoptosis. Pharmacological inhibition of autophagy using 3-methyladenine (3-MA) completely suppressed transitory fusion in vivo in colony assays. Rapamycin did not have a significant effect in the same assays. These results establish the hydroid allorecognition system as a novel model for the study of cell death. PMID:23145018

  5. Tailor-made designer helical peptides that induce mitochondrion-mediated cell death without necrosis.

    PubMed

    Nogami, Kagayaki; Takahama, Kentaro; Okushima, Ayako; Oyoshi, Takanori; Fujimoto, Kazuhisa; Inouye, Masahiko

    2014-11-24

    Managing protein-protein interactions is essential for resolving unknown biological events at the molecular level and developing drugs. We have designed and synthesized a side-chain-crosslinked helical peptides based on the binding domain of a pro-apoptotic protein (Bad) that induces programmed cell death. The peptide showed high helical content and bound to its target, Bcl-XL, more strongly than its non-crosslinked counterparts. When HeLa cells were incubated with the crosslinked peptide, the peptide entered the cytosol across the plasma membrane. The peptide formed a stable complex with Bcl-XL localized at the outer mitochondrial membrane, and this binding event caused the release of cytochrome c from the intermembrane space of mitochondria into the cytosol. This activated the caspase cascade: 70% of HeLa cells died by the apoptosis pathway (without evidence of necrosis).

  6. [Endoscopic treatment of chemical burns to the stomach with mucosa ulceration and necrosis].

    PubMed

    Nalbandova, D A; Sogreshilin, S S; Pinchuk, T P; Klokova, T V; Il'iashenko, K K

    2013-01-01

    The prevalence of acute poisoning with caustic substances in Russia is higher than in other countries and is reported by different authors as accounting for 10-32% cases among the patients admitted to acute poisoning treatment centres. Especially unfavorable prognosis is considered for necrotizing burns to the stomach that increase the risk of severe complications leading to disability of patients. The study aimed at improving the treatment of necrotizing chemical burn to the stomach by the infusion of a 5% Mexidole solution into the edges of a burn lesion at different stages of the treatment course. The paper presents the outcomes of patients who sustained chemical burns to the stomach with mucosa ulceration and necrosis, and provides an assessment of early endoscopic treatment effect.

  7. Epitope mapping of the infectious hematopoietic necrosis virus glycoprotein by flow cytometry.

    PubMed

    Xu, Li-Ming; Liu, Miao; Zhao, Jing-Zhuang; Cao, Yong-Sheng; Yin, Jia-Sheng; Liu, Hong-Bai; Lu, Tongyan

    2014-10-01

    The glycoprotein of infectious hematopoietic necrosis virus was truncated to ten overlapping fragments. All fragments were displayed on the inner membrane of the Escherichia coli periplasm. After disruption of the outer membrane, spheroplasts that had anchored with the glycoprotein fragment were incubated with an anti-glycoprotein polyclonal antibody. Prey pairs were detected and quantitated by flow cytometry with all fragments but one, G2, reacting with the polyclonal antibody. The antigenicity of all ten fragments was analyzed using conventional methods, and epitopes were localized in all fragments, except for G2 and were consistent with FCM analysis. Antigenicity of purified glycoprotein fusion proteins was confirmed by western blotting and ELISA. This method provides a rapid, quantitative and simple strategy for identifying linear B cell epitopes of a given protein.

  8. Detection and transmission of infectious hematopoietic necrosis virus in rainbow trout

    USGS Publications Warehouse

    Amend, Donald F.

    1975-01-01

    Detection and transmission of Infectious Hematopoietic Necrosis Virus in rainbow trout (Salmo gairdneri) was studied at a commercial trout hatchery. Transmission of virus was demonstrated via water, feed and contaminated eggs. If eggs from carrier females were incubated several weeks in virus-free water, the resulting fry did not become infected. However, if fry subsequently became infected they were lifetime carriers. Infectious virus was readily detectable in most tissues of moribund fish; in carriers it was detected in sex products of spawning fish, and in samples from the intestine of post-spawning fish, but not in samples from blood, feces, kidney, or liver. The carrier rate was not significantly different between sexes. It was concluded that adult carriers are the reservoir of infection and that transmission occurs primarily when carriers shed virus and expose susceptible fish or eggs.

  9. Inherited variability of tumor necrosis factor production and susceptibility to infectious disease.

    PubMed

    Knight, J C; Kwiatkowski, D

    1999-01-01

    Tumor necrosis factor (TNF) is a critical mediator of host defense against infection but may cause severe pathology when produced in excess. Individuals vary in the amount of TNF produced when their peripheral blood mononuclear cells are stimulated in vitro, and family studies indicate that much of this variability is genetically determined. Since the TNF response to infection is partly regulated at the transcriptional level, TNF promoter polymorphisms have been the subject of intense interest as potential determinants of disease susceptibility. A single nucleotide polymorphism at nucleotide -308 relative to the transcriptional start site has been associated with susceptibility to severe malaria, leishmaniasis, scarring trachoma, and lepromatous leprosy. Some experimental data indicate that this polymorphism acts to upregulate TNF transcription, but this remains controversial. Detailed analysis of multiple genetic markers at this locus and more sophisticated investigations of TNF transcriptional regulation, in different cell types and with a wide range of stimuli, are required to understand the molecular basis of these disease associations.

  10. Infectious hematopoietic necrosis virus detected by separation and incubation of cells from salmonid cavity fluid.

    USGS Publications Warehouse

    Mulcahy, D.; Batts, W.N.

    1987-01-01

    Infectious hematopoietic necrosis (IHN) virus is usually detected by inoculating susceptible cell cultures with cavity ("ovarian") fluid (CF) from spawning females. We identified additional adult carriers of virus in spawning populations of steelhead trout (Salmo gairdneri) and sockeye salmon (Oncorhynchus nerka) by collecting nonerythrocytic cells from CF samples by low-speed centrifugation, culturing the cells for at least 7 d at 15 °C, and then testing the culture medium for virus. Virus appeared in the cultured cells from some samples of CF that remained negative during incubation. In additional samples of CF from these species, the virus titer increased in cultured cells compared with the titer in the original CF sample. With chinook salmon (O.tshawytscha), no negative samples converted to positive during incubation, but the virus titer was retained in incubated CF cells, but not in cell-free CF.

  11. Detection of infectious haematopoietic necrosis virus in river water and demonstration of waterborne transmission

    USGS Publications Warehouse

    Mulcahy, D.; Pascho, R.J.; Jenes, C.K.

    1983-01-01

    In a study of the possible role of waterborne infectious haematopoietic necrosis virus in transmission of the disease among spawning sockeye salmon, Oncorhynchus nerka (Walbaum), both infection rates and virus titres were higher in fish held at high density in a side channel than in fish in the adjacent river. Virus was never isolated from river water, but was found in water from the side channel at levels ranging from 32.5 to 1600 plaque-forming units (p.f.u.)/ml. Uninfected yearling sockeye salmon held in a box in the side channel developed localized gill infections with IHN virus. The disease did not progress to the viscera until a threshold titre of about 105 p.f.u./g was reached in the gill. The effectiveness of the gill as a barrier limiting development of systemic infections means that waterborne IHN virus probably does not greatly increase the infection rate in a sockeye salmon population during spawning.

  12. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

  13. A simple assay for tumor necrosis factor using HEp-2 target cells.

    PubMed

    Müzes, G; Vien, C V; Gonzalez-Cabello, R; Gergely, P; Feher, J

    1989-09-01

    We developed a sensitive bioassay system for the determination of tumor necrosis factor-alpha (TNF) using HEp-2 adherent human epipharynx carcinoma cells as targets. TNF from separated human monocytes was triggered by lipopolysaccharide (LPS). In a 24 hr 3H-thymidine incorporation assay, TNF-like activity was seen to reproducibly destroy radiolabeled target cells, i.e., inhibits thymidine incorporation and causes detachment of adherent HEp-2 cells. HEp-2 cells were insensitive to human interleukin-1 (IL-1) and interleukin-2 (IL-2). In contrast, human interferon-alpha and gamma were also cytotoxic for target cells. Monocyte supernatants stimulated by LPS, however, failed to contain detectable amounts of interferons. PMID:2484315

  14. Tungsten treatment prevents tumor necrosis factor-induced injury of brain endothelial cells.

    PubMed

    Terada, L S; Willingham, I R; Guidot, D M; Shibao, G N; Kindt, G W; Repine, J E

    1992-02-01

    Exposure to recombinant human tumor necrosis factor-alpha (TNF-alpha) or calcium ionophore (A23187) for 4 h increased (P less than 0.05) lactate dehydrogenase (LDH) release from cultured bovine brain endothelial cells (EC). In contrast, treatment with endotoxin or interleukin-1 did not increase (P greater than 0.05). LDH release from brain EC. Pretreatment with tungsten decreased (P less than 0.05) xanthine oxidase activity in brain EC and decreased (P less than 0.05) LDH release from brain EC following exposure to TNF. Our results suggest that TNF-alpha injures brain microvascular EC and that this effect may be mediated by xanthine oxidase.

  15. Hard metal pneumoconiosis and the association of tumor necrosis factor-alpha.

    PubMed

    Rolfe, M W; Paine, R; Davenport, R B; Strieter, R M

    1992-12-01

    Hard metal pneumoconiosis is a recently recognized occupational lung disease associated with the exposure to cobalt fumes in the workplace. Chronic exposure in susceptible individuals results in interstitial lung disease histopathologically manifested as interstitial fibrosis with an associated mononuclear cell infiltrate and the presence of "cannibalistic" multinucleated giant cells in the alveolar airspaces. The majority of patients present with symptoms of chronic cough and dyspnea. Interestingly, in addition, patients uniformly report significant weight loss out of proportion to their degree of respiratory impairment. In this case report we demonstrate the association of tumor necrosis factor-alpha (TNF) and hard metal (cobalt) pneumoconiosis and suggest that TNF may have a potential role in the etiology of the constitutional symptoms and the pathogenesis of interstitial lung disease.

  16. Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes

    SciTech Connect

    Carroll, M.C.; Katzman, P.; Alicot, E.M.; Koller, B.H.; Geraghty, D.E.; Orr, H.T.; Strominger, J.L.; Spies, T.

    1987-12-01

    The tumor necrosis factor (TNF) ..cap alpha.. and ..beta.. gene pair has been linked in the human major histocompatibility complex to HLA-B, HLA-C, and, tentatively, HLA-E and HLA-A on one side and to the class III complement/steroid 21-hydroxylase gene cluster on the other by pulsed-field gel electrophoresis. The TNF genes are located 200 kilobases (kb) centromeric of HLA-B and about 350 kb telomeric of the class III cluster. Together with previous data on the linkage and structures of the class II and class III regions, a restriction map of the entire human major histocompatibility complex of about 3500 kb has been prepared.

  17. Warfarin skin necrosis mimicking calciphylaxis in a patient with secondary hyperparathyroidism undergoing peritoneal dialysis.

    PubMed

    Park, Jee Eun; Byeon, Seonggyu; Kim, Hee Kyung; Moon, Seong Mi; Moon, Ji Hoon; Jang, Kee-Taek; Lee, Byung-Jae; Jang, Hye Ryoun; Huh, Wooseong; Kim, Dae Joong; Kim, Yoon-Goo; Oh, Ha Young; Lee, Jung Eun

    2016-03-01

    Warfarin skin necrosis (WSN) is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions. PMID:27069859

  18. Production of tumour necrosis factor and interleukin 1 by monocytes of patients with previous Yersinia arthritis.

    PubMed Central

    Repo, H; Jäättelä, M; Leirisalo-Repo, M; Hurme, M

    1988-01-01

    We studied production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by using purified peripheral blood monocytes of patients with previous yersinia arthritis (YA) and of healthy HLA-B27 positive and negative controls. Lipopolysaccharide-exposed cells of HLA-B27 positive and negative patients, and those of HLA-B27 positive controls, generated significantly more TNF than did HLA-B27 negative control cells. There was a positive correlation between the levels of TNF and IL-1. Our results give credence to the view that augmented production of phlogistic mediators may contribute to inflammatory symptoms in patients with HLA-B27 associated disease. PMID:3262459

  19. CD45 negatively regulates tumour necrosis factor and interleukin-6 production in dendritic cells.

    PubMed

    Piercy, Jenny; Petrova, Svetla; Tchilian, Elma Z; Beverley, Peter C L

    2006-06-01

    CD45 is known to regulate signalling through many different surface receptors in diverse haemopoietic cell types. Here we report for the first time that CD45-/- bone marrow dendritic cells (BMDC) are more activated than CD45+/+ cells and that tumour necrosis factor (TNF) and interleukin-6 (IL-6) production by BMDC and splenic dendritic cells (sDC), is increased following stimulation via Toll-like receptor (TLR)3 and TLR9. Nuclear factor-kappaB activation, an important downstream consequence of TLR3 and TLR9 signalling, is also increased in CD45-/- BMDC. BMDC of CD45-/- mice also produce more TNF and IL-6 following stimulation with the cytokines TNF and interferon-alpha. These results show that TLR signalling is increased in CD45-/- dendritic cells and imply that CD45 is a negative regulator of TLR and cytokine receptor signalling in dendritic cells. PMID:16771860

  20. Micropapillary carcinoma of the breast with necrosis-like cell death: a case report.

    PubMed

    Caruso, Rosario Alberto; Cicciarello, Rocco; Gagliardi, Maria Ester; Albiero, Francesca; Costa, Gregorio; Fedele, Francesco; Cavaliere, Renato; Finocchiaro, Giuseppe; Mesiti, Mario; Cavallari, Vittorio

    2008-01-01

    A primary invasive micropapillary carcinoma of the breast in a 46-year-old woman is reported. Histologically, it was composed predominantly of papillary tumor cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells were positive for cytokeratin (CK) 7, estrogen receptor (ER), and progesterone receptor (PR), but negative for p53, CK 20, CD34, c-Erb-B2, CK5, epidermal growth factor receptor (EGFR), vimentin, and c-kit. MUC1 expression was found at the reversed apical membrane of neoplastic cell clusters. Accordingly, electron microscopy showed the lack of basement membrane and presence of microvilli at the basal surface of the tumor cells. Moreover, ultrastructural examination revealed single tumor cell death characterized by patchy condensations of chromatin throughout the nucleus. These nuclear alterations were associated with the occurrence of empty cytoplasmic vacuoles, conferring a necrosis-like phenotype to this cell death. Alternative programmed cell deaths are reviewed and their morphologic distinction is discussed.