Revision Stapedectomy with Necrosis of the Long Process of the Incus: Does the Degree of Necrosis Matter? A Retrospective Clinical Study.

PubMed

Ghonim, Mohamed; Shabana, Yousef; Ashraf, Bassem; Salem, Mohamed

2017-04-01

To discuss the different modalities for managing necrosis of the long process of the incus in revision stapedectomy on the basis of the degree of necrosis and compare the results with those reported in the literature. Thirty-six patients underwent revision stapedectomy with the necrosis of the long process of the incus from 2009 to 2016. The patients were divided into three groups on the basis of the degree of necrosis. For group A (minimal necrosis), augmentation technique with bone cement was performed. For group B (partial necrosis), the cement plug technique was performed. For group C (sever necrosis), malleus relocation with malleovestibulopexy was performed using reshaped necrosed incus. Air and bone conduction thresholds at frequencies of 500-3000 Hz were reviewed pre- and postoperatively using conventional audiometry. The air-bone gap (ABG) and bone conduction thresholds were measured. Postoperative ABG was reduced to <10 dB in 28 cases (77.8%) and <20 dB in all cases (100%). There was no significant change in postoperative bone conduction thresholds. The mean patient follow-up duration was 23 (range, 18-36) months. The cement plug technique was used in 75% of cases. Managing necrosis of the long process of the incus in revision stapedectomy should be considered according to the degree of necrosis. The cement plug technique is considered to be a reasonable option in most cases. Malleus relocation with malleovestibulopexy is an effective alternative to prosthesis.

Recommendations from the INHAND Apoptosis/Necrosis Working Group.

PubMed

Elmore, Susan A; Dixon, Darlene; Hailey, James R; Harada, Takanori; Herbert, Ronald A; Maronpot, Robert R; Nolte, Thomas; Rehg, Jerold E; Rittinghausen, Susanne; Rosol, Thomas J; Satoh, Hiroshi; Vidal, Justin D; Willard-Mack, Cynthia L; Creasy, Dianne M

2016-02-01

Historically, there has been confusion relating to the diagnostic nomenclature for individual cell death. Toxicologic pathologists have generally used the terms "single cell necrosis" and "apoptosis" interchangeably. Increased research on the mechanisms of cell death in recent years has led to the understanding that apoptosis and necrosis involve different cellular pathways and that these differences can have important implications when considering overall mechanisms of toxicity, and, for these reasons, the separate terms of apoptosis and necrosis should be used whenever differentiation is possible. However, it is also recognized that differentiation of the precise pathway of cell death may not be important, necessary, or possible in routine toxicity studies and so a more general term to indicate cell death is warranted in these situations. Morphological distinction between these two forms of cell death can sometimes be straightforward but can also be challenging. This article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This document is intended to serve as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community at large. The specific recommendations are:Use necrosis and apoptosis as separate diagnostic terms.Use modifiers to denote the distribution of necrosis (e.g., necrosis, single cell; necrosis, focal; necrosis, diffuse; etc.).Use the combined term apoptosis/single cell necrosis whenThere is no requirement or need to split the processes, orWhen the nature of cell death cannot be determined with certainty, orWhen both

Comparison between nonspecific and necrosis-avid gadolinium contrast agents in vascular disrupting agent-induced necrosis of rodent tumors at 3.0T.

PubMed

Wang, Huaijun; Miranda Cona, Marlein; Chen, Feng; Li, Junjie; Yu, Jie; Feng, Yuanbo; Peeters, Ronald; De Keyzer, Frederik; Marchal, Guy; Ni, Yicheng

2011-09-01

: To compare a commercial contrast agent (CA) Dotarem and a necrosis-avid CA (NACA) for their ability to evaluate the therapeutic necrosis with a vascular disrupting agent (VDA) on magnetic resonance imaging in rodent liver tumors to determine which could better correlate with the histopathologic outcome. : After the VDA treatment, 16 rats with 32 liver rhabdomyosarcomas were randomized into Dotarem and NACA groups (n = 8 per group) for both interindividual and intraindividual comparisons. T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1-weighted imaging (CE-T1WI), and diffusion-weighted imaging were performed at baseline, after VDA treatment and CA injections. The enhancing efficacy of CAs at immediate and delayed enhancement on CE-T1WI in viable tumor and necrosis was compared. Tumor necrosis ratios calculated from NACA and Dotarem were compared and correlated with gold-standard histopathology. : On the immediate CE-T1WI, viable tumor was enhanced by either CA. On the delayed CE-T1WI at 30 minutes, both CAs failed to demarcate viable tumor from necrosis. At 24 hours post-NACA, the necrosis was clearly distinguished from viable tumor and thus derived necrosis ratio matched that from histopathology (P = 0.99); necrosis ratio from Dotarem was significantly lower than that from NACA and histopathology (P < 0.05, both), with a higher correlation of NACA than that of Dotarem with histopathology (r = 0.99 vs. r = 0.82). : NACA better evaluated VDA-induced tumor necrosis than nonspecific CA on T1WI in tumor models of rat liver. NACA showed a closer correlation with histopathology than nonspecific CA for the delineation of true necrosis. Delayed enhancement on T1WI with nonspecific CA is not suitable for the assessment of VDA-induced tumor necrosis.

Indomethacin induced avascular necrosis of head of femur

PubMed Central

Prathapkumar, K; Smith, I; Attara, G

2000-01-01

Chemically induced avascular necrosis of bone is a well documented entity. Indomethacin is one of the causes of this condition but is often difficult to recognise. Review of the literature shows that only one case of indomethacin induced avascular necrosis has been reported in the English language between 1966 and the present.
The case of a young healthy man, who developed avascular necrosis of head of femur after prolonged administration of indomethacin, is reported here.


Keywords: indomethacin; avascular necrosis PMID:10964124

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.

Using Feily's method prevented scalp necrosis in three patients incline to the scalp recipient necrosis; what is new in prevention of scalp necrosis?

PubMed

Feily, Amir; Feily, Ahmad

2017-01-01

Serious complications arising from surgical hair restoration are relatively uncommon following well-performed and well-planned surgery by skillful surgical techniques, good communication, and postoperative follow-up. Surgical complications often categorized as those which occur in the donor site and the recipient site. In this paper among recipient area complication we focused on recipient area necrosis that arises when an increased number of recipient grafts are utilized and de-vascularization of the scalp occurs as a result of the large wound area due to the dense packing splitting of recipient skin. Recently, Feily et al. explained an interesting method to prevent development of recipient area necrosis following a hair transplant procedure. Herein we reported three cases of dense hair transplantation using the Feilys method that after slitting they troubled by unusual long lasting dark areas on the scalp and they need more than 24 hr's patience for prevention of scalp necrosis. © 2016 Wiley Periodicals, Inc.

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.

Generation of small molecules to interfere with regulated necrosis.

PubMed

Degterev, Alexei; Linkermann, Andreas

2016-06-01

Interference with regulated necrosis for clinical purposes carries broad therapeutic relevance and, if successfully achieved, has a potential to revolutionize everyday clinical routine. Necrosis was interpreted as something that no clinician might ever be able to prevent due to the unregulated nature of this form of cell death. However, given our growing understanding of the existence of regulated forms of necrosis and the roles of key enzymes of these pathways, e.g., kinases, peroxidases, etc., the possibility emerges to identify efficient and selective small molecule inhibitors of pathologic necrosis. Here, we review the published literature on small molecule inhibition of regulated necrosis and provide an outlook on how combination therapy may be most effective in treatment of necrosis-associated clinical situations like stroke, myocardial infarction, sepsis, cancer and solid organ transplantation.

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.

PubMed

Napoletano, Francesco; Gibert, Benjamin; Yacobi-Sharon, Keren; Vincent, Stéphane; Favrot, Clémentine; Mehlen, Patrick; Girard, Victor; Teil, Margaux; Chatelain, Gilles; Walter, Ludivine; Arama, Eli; Mollereau, Bertrand

2017-09-01

The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical function of the initiator caspase Dronc/Caspase 9, independent of its catalytic activity. Prevention of p53-dependent necrosis resulted in testicular hyperplasia, which was reversed by restoring necrosis in spermatogonia. In mouse testes, p53 was required for heat-induced germ cell necrosis, indicating that regulation of necrosis is a primordial function of p53 conserved from invertebrates to vertebrates. Drosophila and mouse spermatogenesis will thus be useful models to identify inducers of necrosis to treat cancers that are refractory to apoptosis.

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis

PubMed Central

Napoletano, Francesco; Vincent, Stéphane; Favrot, Clémentine; Mehlen, Patrick; Girard, Victor; Chatelain, Gilles; Walter, Ludivine; Arama, Eli

2017-01-01

The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical function of the initiator caspase Dronc/Caspase 9, independent of its catalytic activity. Prevention of p53-dependent necrosis resulted in testicular hyperplasia, which was reversed by restoring necrosis in spermatogonia. In mouse testes, p53 was required for heat-induced germ cell necrosis, indicating that regulation of necrosis is a primordial function of p53 conserved from invertebrates to vertebrates. Drosophila and mouse spermatogenesis will thus be useful models to identify inducers of necrosis to treat cancers that are refractory to apoptosis. PMID:28945745

Infected Peri-Pancreatic Necrosis Causing Gallbladder Necrosis by Direct Extension

PubMed Central

Assalia, Ahmad; Schmulevski, Pavel; Meislin, Vladimir; Hashmonai, Moshe

1993-01-01

Acute acalculous cholecystitis may develop in patients suffering from necrotizing pancreatitis. Conversely, acute pancreatitis may complicate acute gallbladder disease. We present a case that lends support to the existence of another possibility: gallbladder necrosis caused by direct extension of the necrotizing pancreatitic process. PMID:8260438

Experimental study of electrolysis-induced hepatic necrosis.

PubMed

Robertson, G S; Wemyss-Holden, S A; Dennison, A R; Hall, P M; Baxter, P; Maddern, G J

1998-09-01

One of the most promising but unexplored methods for treating patients with irresectable liver tumours is electrolysis. This study examined the effect of increasing 'current dose' on the volume of the lesion induced in normal rat liver. A direct current generator, connected to platinum electrodes implanted in the rat liver, was used to examine the effect of (1) varying current doses from 1 to 5 coulombs and (2) electrode separation (2 or 20 mm), on the volume of liver necrosis. There was a significant correlation (P < 0.001) between the current dose and the volume of necrosis produced for each electrode separation. Placing the electrodes 2 mm apart resulted in smaller total volumes of necrosis than placing them 20 mm apart when anode lesions were significantly larger than cathode lesions (P< 0.05). Liver enzymes (aspartate aminotransferase, alanine aminotransferase) were significantly raised 1 day after treatment (P < 0.001) and predicted the total volume of hepatic necrosis (P < 0.001). Predictable and reproducible areas of liver necrosis are produced with electrolysis. If these results extrapolate to larger animal models, this technique has potential for patients with irresectable primary and secondary liver tumours.

Clozapine-induced acute gastrointestinal necrosis: a case report.

PubMed

Osterman, Mark T; Foley, Caitlin; Matthias, Isaac

2017-09-23

Clozapine is known to cause fecal impaction and ileus with resultant colonic necrosis due to compression of colonic mucosa. There are rare reports of clozapine causing necrosis of other portions of the gastrointestinal tract unrelated to constipation. We describe a case of acute necrosis of the upper gastrointestinal tract and small bowel to due to clozapine and quetiapine. A 66-year-old white man with a past medical history of schizophrenia, maintained on clozapine and quetiapine, presented with hypoxic respiratory failure caused by aspiration of feculent emesis due to impacted stool throughout his colon. His constipation resolved with discontinuation of clozapine and quetiapine, and his clinical condition improved. These medicines were restarted after 2 weeks, resulting in acute gastrointestinal necrosis from the mid esophagus through his entire small bowel. He died due to septic shock with Gram-negative rod bacteremia. Clozapine may cause acute gastrointestinal necrosis.

The interplay between regulated necrosis and bacterial infection.

PubMed

Blériot, Camille; Lecuit, Marc

2016-06-01

Necrosis has long been considered as a passive event resulting from a cell extrinsic stimulus, such as pathogen infection. Recent advances have refined this view and it is now well established that necrosis is tightly regulated at the cell level. Regulated necrosis can occur in the context of host-pathogen interactions, and can either participate in the control of infection or favor it. Here, we review the two main pathways implicated so far in bacteria-associated regulated necrosis: caspase 1-dependent pyroptosis and RIPK1/RIPK3-dependent necroptosis. We present how these pathways are modulated in the context of infection by a series of model bacterial pathogens.

Management of Mastectomy Skin Necrosis in Implant Based Breast Reconstruction.

PubMed

Sue, Gloria R; Long, Chao; Lee, Gordon K

2017-05-01

Mastectomy skin necrosis is a significant problem after breast reconstruction. This complication may lead to poor wound healing and need for implant removal, which may delay subsequent oncologic treatment. We sought to characterize factors associated with mastectomy skin necrosis and propose a management algorithm. A retrospective review was performed on consecutive patients undergoing implant-based breast reconstruction by the senior author from 2006 through 2015. Patient-level factors including age, race, body mass index, history of hypertension, history of diabetes, history of smoking, and history of radiation were collected. Surgical factors including type of mastectomy, location of implant placement, and immediate versus delayed reconstruction were collected. The incidence and treatment of mastectomy skin necrosis were analyzed. A total of 293 patients underwent either unilateral or bilateral implant-based breast reconstructions after mastectomy with a total of 471 reconstructed breasts. Mastectomy skin necrosis was observed in 8.1% of reconstructed breasts. Skin necrosis was not associated with age, hypertension, diabetes, prior radiation, or type of mastectomy. The incidence of skin necrosis was higher among smokers (17.9% vs 5.0%, P < 0.001), among patients with higher body mass index (11.4% vs 6.1%, P = 0.05), patients who underwent immediate reconstruction compared to delayed (9.6% vs 0%, P = 0.004), placement of expander under acellular dermal matrix compared with submuscular placement (12.0% vs 5.2%, P = 0.02), and use of higher initial expander fill volume compared with lower fill volume (11.4% vs 5.4%, P = 0.02).The median necrosis size was 8 cm. The median time to treatment was 15 days postoperatively. In 55% of patients minor necrosis was treated with clinic debridement, whereas 43% had larger areas of necrosis requiring operative debridement. The median size treated with clinic debridement was 5.5 cm, compared to 15 cm for operative debridement

Acute Esophageal Necrosis: A Case Series

PubMed Central

Mavilia, Marianna G; Gurvits, Grigoriy E

2018-01-01

Acute esophageal necrosis (AEN) is a particularly rare syndrome with an incidence of only 0.1-0.28%, whose appearance is notable for proximal extensions of black, necrotic appearing mucosa extending proximally in the esophagus and abruptly interrupted at the gastroesophageal junction. In this case series, we explore the cases of two males: one middle-aged and one elderly, who after presenting with emesis, were found to have acute esophageal necrosis on esophagogastroduodenoscopy. PMID:29850386

Papillary Necrosis in Experimental Analgesic Nephropathy

PubMed Central

Saker, B. M.; Kincaid-Smith, Priscilla

1969-01-01

A proprietary aspirin, phenacetin, and caffeine preparation given to rats in a dose equivalent to that taken by patients with analgesic nephropathy produced papillary necrosis in 55%. There was a higher incidence in rats deprived of fluids overnight. Papillary necrosis was not noted in rats receiving twice as much phenacetin. These findings support the argument that phenacetin should not be singled out as the substance responsible for analgesic nephropathy in man. PMID:5762278

Virus inhibition of RIP3-dependent necrosis.

PubMed

Upton, Jason W; Kaiser, William J; Mocarski, Edward S

2010-04-22

Viral infection activates cytokine expression and triggers cell death, the modulation of which is important for successful pathogenesis. Necroptosis is a form of programmed necrosis dependent on two related RIP homotypic interaction motif (RHIM)-containing signaling adaptors, receptor-interacting protein kinases (RIP) 1 and 3. We find that murine cytomegalovirus infection induces RIP3-dependent necrosis. Whereas RIP3 kinase activity and RHIM-dependent interactions control virus-associated necrosis, virus-induced death proceeds independently of RIP1 and is therefore distinct from TNFalpha-dependent necroptosis. Viral M45-encoded inhibitor of RIP activation (vIRA) targets RIP3 during infection and disrupts RIP3-RIP1 interactions characteristic of TNFalpha-induced necroptosis, thereby suppressing both death pathways. Importantly, attenuation of vIRA mutant virus in wild-type mice is normalized in RIP3-deficient mice. Thus, vIRA function validates necrosis as central to host defense against viral infections and highlights the benefit of multiple virus-encoded cell-death suppressors that inhibit not only apoptotic, but also necrotic mechanisms of virus clearance. Copyright 2010 Elsevier Inc. All rights reserved.

Acute Necrotizing Esophagitis Followed by Duodenal Necrosis

PubMed Central

del Hierro, Piedad Magdalena

2011-01-01

Acute Necrotizing Esophagitis is an uncommon pathology, characterized by endoscopic finding of diffuse black coloration in esophageal mucosa and histological presence of necrosis in patients with upper gastrointestinal bleeding. The first case of acute necrotizing esophagitis followed by duodenal necrosis, in 81 years old woman with a positive history of Type 2 Diabetes Mellitus, Hypertension, and usual intake of Nonsteroidal Anti-inflammatory drugs, is reported. Although its etiology remains unknown, the duodenal necrosis suggests that ischemia could be the main cause given that the branches off the celiac axis provide common blood supply to the distal esophageal and duodenal tissue. The massive gastroesophagic reflux and NSAID intake could be involved. PMID:27957030

Cardiolipin plays a role in KCN-induced necrosis.

PubMed

Tsesin, Natalia; Khalfin, Boris; Nathan, Ilana; Parola, Abraham H

2014-10-01

Cardiolipin (CL) is a unique anionic, dimeric phospholipid found almost exclusively in the inner mitochondrial membrane and is essential for the function of numerous enzymes that are involved in mitochondrial energy metabolism. While the role of cardiolipin in apoptosis is well established, its involvement in necrosis is enigmatic. In the present study, KCN-induced necrosis in U937 cells was used as an experimental model to assess the role of CL in necrosis. KCN addition to U937 cells induced reactive oxygen species (ROS) formation, while the antioxidants inhibited necrosis, indicating that ROS play a role in KCN-induced cell death. Further, CL oxidation was confirmed by the monomer green fluorescence of 10-N-nonyl acridine orange (NAO) and by TLC. Utilizing the red fluorescence of the dimeric NAO, redistribution of CL in mitochondrial membrane during necrosis was revealed. We also showed that the catalytic activity of purified adenosine triphosphate (ATP) synthase complex, known to be modulated by cardiolipin, decreased following KCN treatment. All these events occurred at an early phase of the necrotic process prior to rupture of the cell membrane. Furthermore, CL-deficient HeLa cells were found to be resistant to KCN-induced necrosis as compared with the wild type cells. We suggest that KCN, an effective reversible inhibitor of cytochrome oxidase and thereby of the respiratory chain leads to ROS increase, which in turn oxidizes CL (amongst other membrane phospholipids) and leads to mitochondrial membrane lipid reorganization and loss of CL symmetry. Finally, the resistance of CL-deficient cells to necrosis further supports the notion that CL, which undergoes oxidation during necrotic cell death, is an integral part of the milieu of events taking place in mitochondria leading to membrane disorganization and mitochondrial dysfunction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Exploration of the recurrence in radiation brain necrosis after bevacizumab discontinuation

PubMed Central

Zhuang, Hongqing; Yuan, Xiangkun; Chang, Joe Y.; Song, Yongchun; Wang, Junjie; Yuan, Zhiyong; Wang, Xiaoguang; Wang, Ping

2016-01-01

Objective: The aim of the paper was to investigate the recurrence and its causes of radiation brain necrosis following bevacizumab discontinuation. Methods: This study included 14 patients with radiation brain necrosis (confirmed through imaging) after stereotactic radiotherapy for a primary or metastatic brain tumor and who received bevacizumab treatment from June 2011 through December 2014. The patients received bevacizumab at 5 mg/kg, q3-4w, for at least 3 cycles. The T1 signal intensity from enhanced MRI images was used as the evaluation criteria for the brain necrosis treatment efficacy. Results: brain necrosis improved in 13 of the 14 cases (92.9%). However, during follow-up, 10 of the 13 responsive patients (76.9%) exhibited a recurrence in brain necrosis, and a multiple linear regression analysis shows that brain necrosis recurrence was related to the follow-up time after the initial bevacizumab treatment discontinuation. Conclusion: bevacizumab produced good short-term effects for radiation brain necrosis; however, most of the patients would recurrence after bevacizumab is discontinued. Thus, brain necrosis was irreversible. PMID:26934327

Exploration of the recurrence in radiation brain necrosis after bevacizumab discontinuation.

PubMed

Zhuang, Hongqing; Yuan, Xiangkun; Chang, Joe Y; Song, Yongchun; Wang, Junjie; Yuan, Zhiyong; Wang, Xiaoguang; Wang, Ping

2016-07-26

The aim of the paper was to investigate the recurrence and its causes of radiation brain necrosis following bevacizumab discontinuation. This study included 14 patients with radiation brain necrosis (confirmed through imaging) after stereotactic radiotherapy for a primary or metastatic brain tumor and who received bevacizumab treatment from June 2011 through December 2014. The patients received bevacizumab at 5 mg/kg, q3-4w, for at least 3 cycles. The T1 signal intensity from enhanced MRI images was used as the evaluation criteria for the brain necrosis treatment efficacy. brain necrosis improved in 13 of the 14 cases (92.9%). However, during follow-up, 10 of the 13 responsive patients (76.9%) exhibited a recurrence in brain necrosis, and a multiple linear regression analysis shows that brain necrosis recurrence was related to the follow-up time after the initial bevacizumab treatment discontinuation. bevacizumab produced good short-term effects for radiation brain necrosis; however, most of the patients would recurrence after bevacizumab is discontinued. Thus, brain necrosis was irreversible.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment.

PubMed

Karimi, Karen; Odhav, Ashika; Kollipara, Ramya; Fike, Jesse; Stanford, Carol; Hall, John C

Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician's guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.

Biomechanical comparisons between a new avascular necrosis of femaral head stem based on Chinese patients with avascular necrosis and two other designs.

PubMed

Zhang, Qiang; Cheng, Cheng-Kung; Wei, Hung-Wen; Dong, Xiang; Chen, Yi-Ting; Lai, Yu-Shu; Wang, Yan

2013-01-01

There is a relatively high failure rate of the femoral component in patients with avascular necrosis at the intermediate-term follow-up. Improving the geometrical fit of the femoral stem against the medullary canal may help to provide long-term survivorship of the hip replacement for patients with avascular necrosis. We designed a specific stem, based on morphometric studies of proximal femoral canals in Chinese avascular necrosis patients and evaluated the stem by finite element analyses, comparing the novel stem with two commercially available and commonly used stems. The morphometric data from avascular necrosis patients showed specific geometric differences in the proximal femoral canal, including profile curves in both the sagittal and coronary planes than the patients with femoral neck fracture. The shorter stemmed prostheses (Fitmore(®) and our stem) performed better than the longer stemmed prosthesis (VerSys(®)). This is the first study to investigate the femoral geometries of Chinese avascular necrosis patients. Our stem provides better stability and is theoretically beneficial to bone ingrowth, which may increase the long-term stability and fixation of the implant.

Subcutaneous fat necrosis of the newborn.

PubMed

Oswalt, G C; Montes, L F; Cassady, G

1978-08-01

Subcutaneous fat necrosis of the newborn (SFNN) developed in a 1-week-old black boy. His mother had received numerous medications for eclampsia. Birth was by Caesarean section and complicated by meconium aspiration. There were numerous nodules over the back, buttocks and extremities that yielded a caseous-like material. Microscopically, these nodules showed crystallization and necrosis of the fat. Hypoglycemia, pneumonia, oliguria, thrombocytopenia, seizures and urinary infection were associated with the cutaneous problem and led to a fatal outcome 2 weeks after birth.

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

A Case of Trapezium Avascular Necrosis Treated Conservatively.

PubMed

Petsatodis, Evangelos; Ditsios, Konstantinos; Konstantinou, Panagiotis; Pinto, Iosafat; Kostretzis, Lazaros; Theodoroudis, Ioannis; Pilavaki, Mayia

2017-01-01

Avascular necrosis (AVN) of the bones of the wrist most commonly involves the lunate followed by the proximal pole of the scaphoid and the capitate. Trapezium avascular necrosis is extremely rare with only two cases reported in the literature, both of which were treated surgically. In this article, we report a unique case of trapezium avascular necrosis treated conservatively. A 38-year-old man complaining of a 4-month history of mild pain on the base of his right thumb. MRI scan was performed. The clinical presentation and the imaging findings indicated avascular osteonecrosis of the trapezium. The patient was treated with immobilization of the wrist joint for a period of six weeks. Three months later, the patient was free of symptoms and the MRI scan revealed a normal trapezium. AVN of trapezium is extremely rare. Our case shows that immobilization of an early stage avascular necrosis of the trapezium might be a treatment option.

Tumour necrosis factor α secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice.

PubMed

Sendler, Matthias; Dummer, Annegret; Weiss, Frank U; Krüger, Burkhard; Wartmann, Thomas; Scharffetter-Kochanek, Karin; van Rooijen, Nico; Malla, Sudarshan Ravi; Aghdassi, Ali; Halangk, Walter; Lerch, Markus M; Mayerle, Julia

2013-03-01

Acute pancreatitis has long been considered a disorder of pancreatic self-digestion, in which intracellular activation of digestive proteases induces tissue injury. Chemokines, released from damaged pancreatic cells then attract inflammatory cells, whose systemic action ultimately determines the disease severity. In the present work the opposite mechanism is investigated; that is, whether and how inflammatory cells can activate intracellular proteases. Using mice either deficient for the CD18-α subunit of the membrane attack complex-1 (MAC-1) complex or tumour necrosis factor (TNF)α, as well as after depletion of leucocyte subpopulations, pancreatitis was induced by 7-hourly caerulein injections (50 μg/kg, intraperitoneally). Pancreatic acini were coincubated in vitro from wild-type and cathepsin-B-deficient animals with phorbol-12-myristate-13-acetate (PMA)-activated neutrophils and macrophages, caerulein or TNFα, and activities of trypsin, cathepsin-B and caspase-3 were measured, as well as necrosis using fluorogenic substrates. TNFα was inhibited with monospecific antibodies. Deletion of CD18 prevented transmigration of leucocytes into the pancreas during pancreatitis, greatly reduced disease severity and abolished digestive protease activation. Depletion of neutrophils and macrophages equally reduced premature trypsinogen activation and disease severity. In vitro activated neutrophils and macrophages directly induced premature protease activation and cell death in pancreatic acini and stimulation of acini with TNFα induced caspase-3 activation and necrosis via a cathepsin-B and calcium-dependent mechanism. Neutralising antibodies against TNFα and genetic deletion of TNFα prevented leucocyte-induced trypsin activity and necrosis in isolated acini. The soluble inflammatory cell mediator TNFα directly induces premature protease activation and necrosis in pancreatic acinar cells. This activation depends on calcium and cathepsin-B activity. The findings

Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils.

PubMed

Zhu, Xiang; Hogan, Simon P; Molkentin, Jeffery D; Zimmermann, Nives

2016-04-15

Eosinophil degranulation and clusters of free extracellular granules are frequently observed in diverse diseases, including atopic dermatitis, nasal polyposis, and eosinophilic esophagitis. Whether these intact granules are released by necrosis or a biochemically mediated cytolysis remains unknown. Recently, a peptidyl-prolyl isomerase located within the mitochondrial matrix, cyclophilin D (PPIF), was shown to regulate necrotic, but not apoptotic, cell death in vitro in fibroblasts, hepatocytes, and cardiomyocytes. Whether cyclophilin D regulates necrosis in hematopoietic cells such as eosinophils remains unknown. We used PPIF-deficient (Ppif(-/-)) mice to test whether cyclophilin D is required for regulating eosinophil necrosis. PPIF deficiency did not affect eosinophil development or maturation at baseline. After in vitro ionomycin or H2O2 treatment, Ppif(-/-) eosinophils were significantly protected from Ca(2+) overload- or oxidative stress-induced necrosis. Additionally, Ppif(-/-) eosinophils demonstrated significantly decreased necrosis, but not apoptosis, in response to Siglec-F cross-linking, a stimulus associated with eosinophil-mediated processes in vitro and in vivo. When treated with apoptosis inducers, Ppif(+/+) and Ppif(-/-) eosinophils exhibited no significant difference in apoptosis or secondary necrosis. Finally, in a dextran sodium sulfate-induced colitis model, although levels of colitogenic cytokines and eosinophil-selective chemokines were comparable between Ppif(+/+) and Ppif(-/-) mice, the latter exhibited decreased clinical outcomes. This correlated with significantly reduced eosinophil cytolysis in the colon. Collectively, our present studies demonstrate that murine eosinophil necrosis is regulated in vitro and in vivo by cyclophilin D, at least in part, thus providing new insight into the mechanism of eosinophil necrosis and release of free extracellular granules in eosinophil-associated diseases. Copyright © 2016 the American

Avascular necrosis of the trapezoid bone following carpometacarpal arthroplasty.

PubMed

Kane, Patrick; Waryasz, Greg; Katarincic, Julie

2014-03-03

A 58-year-old female developed avascular necrosis of her trapezoid approximately 3 months after undergoing carpometacarpal arthroplasty. The patient was treated conservatively with immobilization and had complete resolution of her clinical symptoms during her year of follow-up. Additionally, radiographic examination showed complete restoration of the height of her trapezoid approximately 1 year after the index procedure. Avascular necrosis of the trapezoid is extremely rare with very few cases described in the literature. This is the first description of avascular necrosis following carpometacarpal arthroplasty.

Is it better to include necrosis in apparent diffusion coefficient (ADC) measurements? The necrosis/wall ADC ratio to differentiate malignant and benign necrotic lung lesions: Preliminary results.

PubMed

Karaman, Adem; Durur-Subasi, Irmak; Alper, Fatih; Durur-Karakaya, Afak; Subasi, Mahmut; Akgun, Metin

2017-10-01

To determine whether the use of necrosis/wall apparent diffusion coefficient (ADC) ratios in the differentiation of necrotic lung lesions is more reliable than measuring the wall alone. In this retrospective study, a total of 76 patients (54 males and 22 females, 71% vs. 29%, with a mean age of 53 ± 18 years, range, 18-84) were enrolled, 33 of whom had lung carcinoma and 43 had a benign necrotic lung lesion. A 3T scanner was used. The calculation of the necrosis/wall ADC ratio was based on ADC values measured from necrosis and the wall of the lesions by diffusion-weighted imaging (DWI). Statistical analyses were performed with the independent samples t-test and receiver operating characteristic analysis. Intraobserver and interobserver reliability were calculated for ADC values of wall and necrosis. The mean necrosis/wall ADC ratio was 1.67 ± 0.23 for malignant lesions and 0.75 ± 0.19 for benign lung lesions (P < 0.001). To estimate malignancy the area under the curve (AUC) values for necrosis ADC, wall ADC, and the necrosis/wall ADC ratio were 0.720, 0.073, and 0.997, respectively. A wall/necrosis ADC ratio cutoff value of 1.12 demonstrated a 100% sensitivity and 98% specificity in the estimation of malignancy. Positive predictive value was 100%, and negative predictive value 98% and diagnostic accuracy 99%. There was a good intraobserver and interobserver reliability for wall and necrosis. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating lung carcinoma from benign necrotic lung lesions than measuring the wall alone. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1001-1006. © 2017 International Society for Magnetic Resonance in Medicine.

Umbilical necrosis rates after abdominal-based microsurgical breast reconstruction.

PubMed

Ricci, Joseph A; Kamali, Parisa; Becherer, Babette E; Curiel, Daniel; Wu, Winona; Tobias, Adam M; Lin, Samuel J; Lee, Bernard T

2017-07-01

Umbilical stalk necrosis represents a rare, yet important complication after abdominal-based microsurgical breast reconstruction, which is both underrecognized and understudied in the literature. Once identified, umbilical reconstruction can be an extremely challenging problem. All consecutive breast free flaps at a single institution from February 2004 to February 2016 were reviewed, excluding non-abdominal-based flaps. Patients were divided based on the development of umbilical necrosis postoperatively. Demographics, surgical characteristics, and other complications were compared between the groups. A total of 918 patients met the inclusion criteria, with 29 developing umbilical necrosis identified (3.2%). Patients developing necrosis tended to be older (49.4 yrs versus 52.9 yrs; P < 0.01); have higher BMI (31.3 versus 27.8; P < 0.01); and were more likely to be smokers (27.5% versus 11.6%; P = 0.01). Umbilical necrosis was also associated with increased flap weight (830 g versus 656 g; P < 0.01), decreased time of perforator dissection (151 min versus 169 min; P = 0.02); bilateral cases (68.9% versus 44.7%; P < 0.01), and increased number of perforators per flap (2.5 versus 2.2; P = 0.03). There was no association with flap type (deep inferior epigastric perforator, superficial inferior epigastric artery, or free TRAM), diabetes, previous abdominal surgery, or use of preoperative imaging. Umbilical necrosis was not associated with any concomitant complications. Umbilical stalk necrosis was found to occur in 3.2% of patients and was associated with several preoperative comorbidities and intraoperative characteristics. This information should help influence intraoperative decision-making to prevent the development of this undesirable complication. Copyright © 2017 Elsevier Inc. All rights reserved.

Fat necrosis in autologous abdomen-based breast reconstruction: a systematic review.

PubMed

Khansa, Ibrahim; Momoh, Adeyiza O; Patel, Priti P; Nguyen, John T; Miller, Michael J; Lee, Bernard T

2013-03-01

Fat necrosis is a common and potentially exasperating complication of autologous breast reconstruction. The authors performed a systematic review of the English literature on autologous breast reconstruction to determine significant patient and surgical factors that are predictors of postoperative fat necrosis. A PubMed search using the terms "fat necrosis" and "breast reconstruction" was conducted. Articles were screened using predetermined inclusion and exclusion criteria. Data collected included patient characteristics, reconstructive techniques used, and the specific postoperative morbidity of interest. Patient cohorts were pooled, and the incidence of fat necrosis was calculated in the presence and absence of each risk factor. Chi-square analysis was applied, and p < 0.05 was considered statistically significant. Of 172 articles found, 70 met the inclusion criteria. The mean rate of fat necrosis was 11.3 percent. Deep inferior epigastric artery perforator flaps had the highest rate of fat necrosis (14.4 percent), followed by pedicled transverse rectus abdominis musculocutaneous (12.3 percent), superficial inferior epigastric artery (8.1 percent), and free transverse rectus abdominis musculocutaneous flaps (6.9 percent). Significant predictors of fat necrosis included obesity (p = 0.035), prereconstruction irradiation (p = 0.022), postreconstruction irradiation (p < 0.001), active smoking (p < 0.001), and abdominal scars (p = 0.05). Protective factors included supercharging (p < 0.001) and bilateral reconstruction (p = 0.01). Although there is little agreement in the literature regarding risk factors for fat necrosis, the authors were able to demonstrate several significant predictors by systematically analyzing 70 articles. Improved knowledge of the risk factors for fat necrosis can help surgeons provide improved preoperative counseling and take measures to minimize the risk of this complication.

Atraumatic Pantalar Avascular Necrosis in a Patient With Alcohol Dependence.

PubMed

Callachand, Fayaz; Milligan, David; Wilson, Alistair

2016-01-01

In the United States, an estimated 10,000 to 20,000 new cases of avascular necrosis are diagnosed each year. We present an unusual case of atraumatic avascular necrosis with widespread hindfoot and midfoot involvement. A 62-year-old female with a history of alcohol dependence and smoking, who had previously been treated for avascular necrosis of the knee, presented with right-sided foot pain and difficulty weightbearing. Imaging studies revealed extensive avascular necrosis of the hindfoot and midfoot, which precluded simple surgical intervention. The patient was followed up for 18 months. In the last 8 months of the 18-month period, the patient managed her symptoms using an ankle-foot orthosis. A diagnosis of avascular necrosis should be considered in patients with atraumatic foot and ankle pain, especially in the presence of risk factors such as alcohol excess and smoking. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

The recent progress of the mechanism and regulation of tumor necrosis in colorectal cancer.

PubMed

Zhang, Xi; Chen, Lirong

2016-02-01

In colorectal cancer (CRC), despite the complex inducing and regulating mechanism in necrosis progress, the prognostic value of tumor necrosis has been reported. It is generally recognized that necrosis is associated with many process involving severe hypoxia, inflammatory responses and angiogenesis, all of which contribute to promote tumor growth and poor prognosis. In addition to local hypoxia, regulation by RIP kinase and the conversion from apoptosis to necrosis can result in necrosis also. Recent studies showed necrosis can be a histopathologic characteristic for special molecular phenotype of CRC. A novel and attractive complementary treatment, tumor necrosis therapy, using radiolabelled compounds avid for necrosis has emerged. However, the complicated regulatory mechanisms of tumor necrosis were rarely reported in CRC, and we collected and reviewed these effect and relevance in CRC.

Endothelial necrosis at 1h post-burn predicts progression of tissue injury

PubMed Central

Hirth, Douglas; McClain, Steve A.; Singer, Adam J.; Clark, Richard A.F.

2013-01-01

Burn injury progression has not been well characterized at the cellular level. To define burn injury progression in terms of cell death, histopathologic spatiotemporal relationships of cellular necrosis and apoptosis were investigated in a validated porcine model of vertical burn injury progression. Cell necrosis was identified by High Mobility Group Box 1 protein and apoptosis by Caspase 3a staining of tissue samples taken 1h, 24h and 7 days post-burn. Level of endothelial cell necrosis at 1h was predictive of level of apoptosis at 24h (Pearson's r=0.87) and of level of tissue necrosis at 7 days (Pearson's r=0.87). Furthermore, endothelial cell necrosis was deeper than interstitial cell necrosis at 1h (p<0.001). Endothelial cell necrosis at 1h divided the zone of injury progression (Jackson's zone of stasis) into an upper subzone with necrotic endothelial cells and initially viable adnexal and interstitial cells at 1h that progressed to necrosis by 24h, and a lower zone with initially viable endothelial cells at 1h, but necrosis and apoptosis of all cell types by 24h. Importantly, this spatiotemporal series of events and rapid progression resembles myocardial infarction and stroke, and implicates mechanisms of these injuries, ischemia, ischemia reperfusion, and programmed cell death, in burn progression. PMID:23627744

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.

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. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

PubMed

Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

[Skin necrosis during long-term fluindione treatment revealing protein C deficiency].

PubMed

Merklen-Djafri, C; Mazurier, I; Samama, M-M; Alhenc-Gelas, M; Tortel, M-C; Cribier, B; Roth, B; Batard, M-L

2012-03-01

Cutaneous necrosis is a rare complication of vitamin K antagonist therapy. It presents as cutaneous hemorrhagic necrosis and usually occurs at the start of treatment. We describe an atypical case of recurrent skin necrosis after two years of treatment with fluindione. A 70-year old woman with a history of venous thromboembolism and obesity presented with a large haemorrhagic necrosis of the abdominal wall. She had been treated with fluindione for two years. Genetic protein C deficiency was discovered. Resumption of vitamin K antagonist therapy was followed by recurrence of skin necrosis despite concomitant administration of heparin. Treatment with vitamin K antagonists could not be continued. This observation is unusual due to the late onset of skin necrosis. The condition usually begins shortly after initiation of vitamin K antagonist therapy, generally between the third and the sixth day of treatment. It is due to a transient hypercoagulable state in patients with protein C deficiency or, in rare cases, protein S deficiency. This late-onset skin necrosis, occurring many years after initiation of anticoagulant therapy, may be explained by a sudden worsening of pre-existing protein C deficiency due to infectious and iatrogenic factors. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Fueling the Flames: Mammalian Programmed Necrosis in Inflammatory Diseases

PubMed Central

Chan, Francis Ka-Ming

2012-01-01

Programmed necrosis or necroptosis is an inflammatory form of cell death driven by TNF-like death cytokines, toll-like receptors, and antigen receptors. Unlike necrosis induced by physical trauma, a dedicated pathway is involved in programmed necrosis. In particular, a kinase complex composed of the receptor interacting protein kinase 1 (RIPK1) and RIPK3 is a central step in necrotic cell death. Assembly and activation of this RIPK1–RIPK3 “necrosome” is critically controlled by protein ubiquitination, phosphorylation, and caspase-mediated cleavage events. The molecular signals cumulate in formation of intracellular vacuoles, organelle swelling, internal membrane leakage, and eventually plasma membrane rupture. These morphological changes can result in spillage of intracellular adjuvants to promote inflammation and further exacerbate tissue injury. Because of the inflammatory nature of necrosis, it is an attractive pathway for therapeutic intervention in acute inflammatory diseases. PMID:23125016

Computed Tomography Evaluation of Esophagogastric Necrosis After Caustic Ingestion.

PubMed

Chirica, Mircea; Resche-Rigon, Matthieu; Zagdanski, Anne Marie; Bruzzi, Matthieu; Bouda, Damien; Roland, Eric; Sabatier, François; Bouhidel, Fatiha; Bonnet, Francine; Munoz-Bongrand, Nicolas; Marc Gornet, Jean; Sarfati, Emile; Cattan, Pierre

2016-07-01

Endoscopy is the standard of care for emergency patient evaluation after caustic ingestion. However, the inaccuracy of endoscopy in determining the depth of intramural necrosis may lead to inappropriate decision-making with devastating consequences. Our aim was to evaluate the use of computed tomography (CT) for the emergency diagnostic workup of patients with caustic injuries. In a prospective study, we used a combined endoscopy-CT decision-making algorithm. The primary outcome was pathology-confirmed digestive necrosis. The respective utility of CT and endoscopy in the decision-making process were compared. Transmural endoscopic necrosis was defined as grade 3b injuries; signs of transmural CT necrosis included absence of postcontrast gastric/ esophageal-wall enhancement, esophageal-wall blurring, and periesophageal-fat blurring. We included 120 patients (59 men, median age 44 years). Emergency surgery was performed in 24 patients (20%) and digestive resection was completed in 16. Three patients (3%) died and 28 patients (23%) experienced complications. Pathology revealed transmural necrosis in 9/11 esophagectomy and 16/16 gastrectomy specimens. Severe oropharyngeal injuries (P = 0.015), increased levels of blood lactate (P = 0.007), alanine aminotransferase (P = 0.027), bilirubin (P = 0.005), and low platelet counts (P > 0.0001) were predictive of digestive necrosis. Decision-making relying on CT alone or on a combined CT-endoscopy algorithm was similar and would have spared 19 unnecessary esophagectomies and 16 explorative laparotomies compared with an endoscopy-alone algorithm. Endoscopy did never rectify a wrong CT decision. Emergency decision-making after caustic injuries can rely on CT alone.

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Take my breath away: necrosis in kidney transplants kills the lungs!

PubMed

Vanden Berghe, Tom; Linkermann, Andreas

2015-04-01

Necrosis is not only a regulated process, it is an interconnected molecular network allowing different genetically encoded forms that are more or less immunogenic. Zhao et al. elegantly illustrate this concept, underscore the need for combination therapy to successfully interfere with regulated necrosis, and identify the role of regulated necrosis in the pathophysiology of remote lung injury.

RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma.

PubMed

Das, Arabinda; McDonald, Daniel G; Dixon-Mah, Yaenette N; Jacqmin, Dustin J; Samant, Vikram N; Vandergrift, William A; Lindhorst, Scott M; Cachia, David; Varma, Abhay K; Vanek, Kenneth N; Banik, Naren L; Jenrette, Joseph M; Raizer, Jeffery J; Giglio, Pierre; Patel, Sunil J

2016-06-01

Radiation-induced necrosis (RN) is a relatively common side effect of radiation therapy for glioblastoma. However, the molecular mechanisms involved and the ways RN mechanisms differ from regulated cell death (apoptosis) are not well understood. Here, we compare the molecular mechanism of cell death (apoptosis or necrosis) of C6 glioma cells in both in vitro and in vivo (C6 othotopically allograft) models in response to low and high doses of X-ray radiation. Lower radiation doses were used to induce apoptosis, while high-dose levels were chosen to induce radiation necrosis. Our results demonstrate that active caspase-8 in this complex I induces apoptosis in response to low-dose radiation and inhibits necrosis by cleaving RIP1 and RI. When activation of caspase-8 was reduced at high doses of X-ray radiation, the RIP1/RIP3 necrosome complex II is formed. These complexes induce necrosis through the caspase-3-independent pathway mediated by calpain, cathepsin B/D, and apoptosis-inducing factor (AIF). AIF has a dual role in apoptosis and necrosis. At high doses, AIF promotes chromatinolysis and necrosis by interacting with histone H2AX. In addition, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. Analysis of inflammatory markers in matched plasma and cerebrospinal fluid (CSF) isolated from in vivo specimens demonstrated the upregulation of chemokines and cytokines during the necrosis phase. Using RIP1/RIP3 kinase specific inhibitors (Nec-1, GSK'872), we also establish that the RIP1-RIP3 complex regulates programmed necrosis after either high-dose radiation or TNF-α-induced necrosis requires RIP1 and RIP3 kinases. Overall, our data shed new light on the relationship between RIP1/RIP3-mediated programmed necrosis and AIF-mediated caspase-independent programmed necrosis in glioblastoma.

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

MedlinePlus

... Email Facebook Twitter Home Health Conditions TRAPS Tumor necrosis factor receptor-associated periodic syndrome Printable PDF Open ... to view the expand/collapse boxes. Description Tumor necrosis factor receptor-associated periodic syndrome (commonly known as ...

Pancreatic Necrosis and Gas in the Retroperitoneum: Treatment with Antibiotics Alone.

PubMed

Rasslan, Roberto; da Costa Ferreira Novo, Fernando; Rocha, Marcelo Cristiano; Bitran, Alberto; de Souza Rocha, Manoel; de Oliveira Bernini, Celso; Rasslan, Samir; Utiyama, Edivaldo Massazo

2017-02-01

To present our experience in the management of patients with infected pancreatic necrosis without drainage. The records of patients with pancreatic necrosis admitted to our facility from 2011 to 2015 were retrospectively reviewed. We identified 61 patients with pancreatic necrosis. Six patients with pancreatic necrosis and gas in the retroperitoneum were treated exclusively with clinical support without any type of drainage. Only 2 patients had an APACHE II score >8. The first computed tomography scan revealed the presence of gas in 5 patients. The Balthazar computed tomography severity index score was >9 in 5 of the 6 patients. All patients were treated with antibiotics for at least 3 weeks. Blood cultures were positive in only 2 patients. Parenteral nutrition was not used in these patients. The length of hospital stay exceeded three weeks for 5 patients; 3 patients had to be readmitted. A cholecystectomy was performed after necrosis was completely resolved; pancreatitis recurred in 2 patients before the operation. No patients died. In selected patients, infected pancreatic necrosis (gas in the retroperitoneum) can be treated without percutaneous drainage or any additional surgical intervention. Intervention procedures should be performed for patients who exhibit clinical and laboratory deterioration.

Gastric Necrosis due to Acute Massive Gastric Dilatation.

PubMed

Aydin, Ibrahim; Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

2013-01-01

Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature.

Gastric Necrosis due to Acute Massive Gastric Dilatation

PubMed Central

Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

2013-01-01

Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature. PMID:23983714

Widespread Skin Necrosis Secondary to Gemcitabine Therapy.

PubMed

Zito, Patrick M; Gonzalez, Adrianna M; Fox, Joshua D; Cronin, Megan; Mackrides, Nicholas; Kirsner, Robert S; Nichols, Anna J

2018-05-01

Gemcitabine, a pyrimidine nucleoside analogue, is an oncologic agent used in the treatment of cutaneous T-cell lymphoma (CTCL). Common dermatologic reactions associated with gemcitabine include alopecia, mild skin rash, and mucositis but skin necrosis is exceptional. Herein we present an unusual case of widespread skin necrosis mimicking toxic epidermal necrolysis in a 45-year-old woman receiving gemcitabine therapy for stage IIIA cutaneous T-cell lymphoma. This is the first reported case of a TEN-like reaction subsequent to gemcitabine treatment. J Drugs Dermatol. 2018;17(5):582-585.

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.

Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

PubMed

Bahia, Malkeet S; Silakari, Om

2010-05-01

Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

Pancreatic necrosis in New World camelids: 11 cases (1990-1998).

PubMed

Pearson, E G; Snyder, S P

2000-07-15

To determine clinical, clinicopathologic, and postmortem abnormalities in New World camelids with pancreatic necrosis. Retrospective study. 10 llamas and 1 alpaca. Medical records of animals in which a diagnosis of pancreatic necrosis had been made on the basis of histologic examination of necropsy specimens or on the basis of clinical signs and results of clinicopathologic testing were reviewed. The initial owner complaint varied, and various other conditions were diagnosed. Clinical and clinicopathologic abnormalities were vague. Amylase activity was higher in abdominal fluid than in serum in 5 of 7 animals, and lipase activity was higher in abdominal fluid than in serum in all 7. Four animals survived, and 7 died or were euthanatized. Only 1 of the animals that died had marked inflammation of the pancreatic parenchyma. All 7 had necrosis and saponification of fat in and surrounding the pancreas. Results suggest that pancreatic necrosis may develop in New World camelids, but clinical signs are vague, and the condition may easily be confused with other diseases. The only laboratory test that appeared to be helpful in the antemortem diagnosis of pancreatic necrosis was comparison of amylase and lipase activities in abdominal fluid and serum.

Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.

PubMed

Ma, Yifang; Zheng, Chutian; Feng, Yiping; Xu, Qingsheng

2017-09-01

Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.

An Overview of Pathways of Regulated Necrosis in Acute Kidney Injury.

PubMed

Kers, Jesper; Leemans, Jaklien C; Linkermann, Andreas

2016-05-01

Necrosis is the predominant form of regulated cell death in acute kidney injury (AKI) and represents results in the formation of casts that appear in the urine sedimentation, referred to as muddy brown casts, which are part of the diagnosis of AKI. Pathologists referred to this typical feature as acute tubular necrosis. We are only beginning to understand the dynamics and the molecular pathways that underlie such typical necrotic morphology. In this review, we provide an overview of candidate pathways and summarize the emerging evidence for the relative contribution of these pathways of regulated necrosis, such as necroptosis, ferroptosis, mitochondrial permeability transition-mediated regulated necrosis, parthanatos, and pyroptosis. Inhibitors of each of these pathways are available, and clinical trials may be started after the detection of the most promising drug targets, which will be discussed here. With the global burden of AKI in mind, inhibitiors of regulated necrosis represent promising means to prevent this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

PubMed

Nuttall, T J; Burrow, R; Fraser, I; Kipar, A

2005-05-01

An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.

Bacteria-induced phagocyte secondary necrosis as a pathogenicity mechanism.

PubMed

Silva, Manuel T

2010-11-01

Triggering of phagocyte apoptosis is a major virulence mechanism used by some successful bacterial pathogens. A central issue in the apoptotic death context is that fully developed apoptosis results in necrotic cell autolysis (secondary necrosis) with release of harmful cell components. In multicellular animals, this occurs when apoptosing cells are not removed by scavengers, mainly macrophages. Secondary necrotic lysis of neutrophils and macrophages may occur in infection when extensive phagocyte apoptosis is induced by bacterial cytotoxins and removal of apoptosing phagocytes is defective because the apoptotic process exceeds the available scavenging capacity or targets macrophages directly. Induction of phagocyte secondary necrosis is an important pathogenic mechanism, as it combines the pathogen evasion from phagocyte antimicrobial activities and the release of highly cytotoxic molecules, particularly of neutrophil origin, such as neutrophil elastase. This pathogenicity mechanism therefore promotes the unrestricted multiplication of the pathogen and contributes directly to the pathology of several necrotizing infections, where extensive apoptosis and necrosis of macrophages and neutrophils are present. Here, examples of necrotizing infectious diseases, where phagocyte secondary necrosis is implicated, are reviewed.

Gastric volvulus with partial and complete gastric necrosis

PubMed Central

Shukla, Ram Mohan; Mandal, Kartik Chandra; Maitra, Sujay; Ray, Amit; Sarkar, Ruchirendu; Mukhopadhyay, Biswanath; Bhattacharya, Malay

2014-01-01

Here, we report two interesting cases of gastric necrosis in acute gastric volvulus due to eventration of the diaphragm. Both the cases presented with a significant challenge and were managed successfully. The management of the cases is presented and relevant literature is discussed. To the best of our knowledge, this is the first case report of gastric volvulus with gastric necrosis requiring complete and partial gastrectomy in the available English literature. PMID:24604987

Bladder necrosis: 'A man without a bladder'.

PubMed

Bosschieter, Judith; Oudshoorn, Frederik H K; Meuleman, Eric J H; Nieuwenhuijzen, Jakko A

2018-02-17

Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical impact and network of determinants of tumour necrosis in colorectal cancer

PubMed Central

Väyrynen, Sara A; Väyrynen, Juha P; Klintrup, Kai; Mäkelä, Jyrki; Karttunen, Tuomo J; Tuomisto, Anne; Mäkinen, Markus J

2016-01-01

Background: The disease outcome in colorectal cancer (CRC) can vary in a wide range within the same tumour stage. The aim of this study was to clarify the prognostic value and the determinants of tumour necrosis in CRC. Methods: The areal proportion (%) of tumour tissue showing coagulative necrosis was evaluated in a cohort of 147 CRC patients and correlated with basic clinicopathological characteristics, microvascular density (MVD), cell proliferation rate, KRAS and BRAF mutations, and survival. To validate the prognostic significance of tumour necrosis, an independent cohort of 418 CRC patients was analysed. Results: Tumour necrosis positively correlated with tumour stage (P=8.5E−4)—especially with T class (4.0E−6)—and inversely correlated with serrated histology (P=0.014), but did not significantly associate with cell proliferation rate, MVD, and KRAS or BRAF mutation. Abundant (10% or more) tumour necrosis associated with worse disease-free survival independent of stage and other biological or clinicopathological characteristics in both cohorts, and the adverse effect was directly related to its extent. High CD105 MVD was also a stage independent marker for worse disease-free survival. Conclusions: Tumour necrosis percentage is a relevant histomorphological prognostic indicator in CRC. More studies are needed to disclose the mechanisms of tumour necrosis. PMID:27195424

Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

PubMed

Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko

2015-12-01

Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

Mucoperiosteal Flap Necrosis after Primary Palatoplasty in Patients with Cleft Palate

PubMed Central

Cotrina-Rabanal, Omar; Barrenechea-Tarazona, Luis; Vargas-Chanduvi, Roberto; Paredes-Aponte, Luis; Romero-Narvaez, Carolina

2017-01-01

Background The prevalence of flap necrosis after palatoplasty in patients with cleft palate. The prevalence of mucoperiosteal flap necrosis after palatoplasty remains unknown, and this complication is rare. This event is highly undesirable for both the patient and the surgeon. We present here a new scale to evaluate the degree of hypoplasia of the palate and identify patients with cleft palate at high risk for the development of this complication. Methods In this case series, a 20-year retrospective analysis (1994–2014) identified patients from our records (medical records and screening day registries) with nonsyndromic cleft palate who underwent operations at 3 centers. All of these patients underwent operations using 2-flap palatoplasty and also underwent a physical examination with photographs and documentation of the presence of palatal flap necrosis after primary palatoplasty. Results Palatal flap necrosis was observed in 4 cases out of 1,174 palatoplasties performed at these centers. The observed prevalence of palatal flap necrosis in these groups was 0.34%. Conclusions The prevalence of flap necrosis can be reduced by careful preoperative planning, and prevention is possible. The scale proposed here may help to prevent this complication; however, further studies are necessary to validate its utility. PMID:28573096

Histopathological changes in the pancreas of cattle with abdominal fat necrosis

PubMed Central

TANI, Chikako; PRATAKPIRIYA, Watanyoo; TANI, Mineto; YAMAUCHI, Takenori; HIRAI, Takuya; YAMAGUCHI, Ryoji; ANO, Hitoshi; KATAMOTO, Hiromu

2016-01-01

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process. PMID:27795463

Histopathological changes in the pancreas of cattle with abdominal fat necrosis.

PubMed

Tani, Chikako; Pratakpiriya, Watanyoo; Tani, Mineto; Yamauchi, Takenori; Hirai, Takuya; Yamaguchi, Ryoji; Ano, Hitoshi; Katamoto, Hiromu

2017-01-20

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process.

[Effect of vascular endothelial growth factor and tumor necrosis factor receptor for treatment of avascular necrosis of the femoral head in rabbits].

PubMed

Hu, Zhi-ming; Zhou, Ming-qian; Gao, Ji-min

2008-12-01

To evaluate the therapeutic effect of vascular endothelial growth factor (VEGF) and tumor necrosis factor receptor (TNFR) on avascular necrosis of the femoral head in rabbits. Avascular necrosis of the femoral head was induced in 26 New Zealand white rabbits by injections of horse serum and prednisolone. The rabbits were then divided into VEGF/TNFR treatment group, VEGF treatment group, and untreated model group, with another 4 normal rabbits as the normal control group. In the two treatment groups, the therapeutic agents were injected percutaneously into the femoral head. Enzyme-linked immunosorbent assay was performed to determine the concentration of TNF-alpha in rabbit serum followed by pathological examination of the changes in the bone tissues, bone marrow hematopoietic tissue and the blood vessels in the femoral head. Compared with the model group, the rabbits with both VEGF and TNFR treatment showed decreased serum concentration of TNF-alpha with obvious new vessel formation, decreased empty bone lacunae in the femoral head and hematopoietic tissue proliferation in the bone marrow cavity. Percutaneous injection of VEGF and TNFR into the femoral head can significantly enhance bone tissue angiogenesis and ameliorate osteonecrosis in rabbits with experimental femoral head necrosis.

United Kingdom nationwide study of avascular necrosis of the jaws including bisphosphonate-related necrosis.

PubMed

Rogers, S N; Palmer, N O A; Lowe, D; Randall, C

2015-02-01

We aimed to record all new patients who presented to departments of oral surgery, oral medicine, and oral and maxillofacial surgery, and to dental hospitals in the UK, with avascular necrosis of the jaws including bisphosphonate-related necrosis (BRONJ) over a 2-year period (1 June 2009-31 May 2011). They were eligible irrespective of age, cause, or coexisting conditions. Data on incidence, clinical characteristics, risk factors, and coexisting conditions were collected. A total of 383 cases were registered: 369 were described as BRONJ, 5 as avascular necrosis, and 9 were unknown. Bisphosphonates had been given orally in 207 (56%), intravenously in 125 (34%), both orally and intravenously in 27 (7%), and was unknown in 9 (2%); one had been given denosumab. The main risk factor was dental extraction, and the mandible was commonly affected. The median duration of administration until onset of BRONJ was 3 years in those treated intravenously and 4 years in those treated orally. Levels of engagement with the study varied between regions, and extrapolation from the 2 most involved (Merseyside and Northern Ireland) found around 8.2-12.8 cases/million/year, which is 508-793 patients/year across the UK. To our knowledge this is one of the first studies to estimate national rates of BRONJ. It confirms that the risk and incidence are low. With changes in trends for antiresorptive bone medication, and increasing numbers of elderly people, it would be useful to repeat the registration in the future. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Effect of bevacizumab on radiation necrosis of the brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.

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 radiationmore » 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.« less

Uterine necrosis following pelvic arterial embolization for post-partum hemorrhage: review of the literature.

PubMed

Poujade, Olivier; Ceccaldi, Pierre François; Davitian, Carine; Amate, Pascale; Chatel, Paul; Khater, Carine; Aflak, Nizar; Vilgrain, Valérie; Luton, Dominique

2013-10-01

Uterine necrosis is one of the rarest complications following pelvic arterial embolization for postpartum hemorrhage (PPH). With the increasing incidence of cesarean section and abnormal placental localization (placenta previa) or placental invasion (placenta accreta/increta/percreta), more and more cases of uterine necrosis after embolization are being diagnosed and reported. Pelvic computed tomography or magnetic resonance imaging provides high diagnostic accuracy, and surgical management includes hysterectomy. We performed a Medline database query following the first description of uterine necrosis after pelvic embolization (between January 1985 and January 2013). Medical subheading search words were the following: "uterine necrosis"; "embolization"; "postpartum hemorrhage". Seventeen citations reporting at least one case of uterine necrosis after pelvic embolization for PPH were included, with a total of 19 cases. This literature review discusses the etiopathogenesis, clinical and therapeutic aspects of uterine necrosis following pelvic arterial embolization, and guidelines are detailed. The mean time interval between pelvic embolization and diagnosis of uterine necrosis was 21 days (range 9-730). The main symptoms of uterine necrosis were fever, abdominal pain, menorrhagia and leukorrhea. Surgical management included total hysterectomy (n=15, 78%) or subtotal hysterectomy (n=2, 10%) and partial cystectomy with excision of the necrotic portion in three cases of associated bladder necrosis (15%). Uterine necrosis was partial in four cases (21%). Regarding the pathophysiology, four factors may be involved in uterine necrosis: the size and nature of the embolizing agent, the presence of the anastomotic vascular system and the embolization technique itself with the use of free flow embolization. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

miR-874 regulates myocardial necrosis by targeting caspase-8

PubMed Central

Wang, K; Liu, F; Zhou, L-Y; Ding, S-L; Long, B; Liu, C-Y; Sun, T; Fan, Y-Y; Sun, L; Li, P-F

2013-01-01

Cardiomyocyte death is an important reason for the cardiac syndromes, such as heart failure (HF) and myocardial infarction (MI). In the heart diseases, necrosis is one of the main forms of cell death. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. Hitherto, it is not yet clear whether miRNA can regulate necrosis in cardiomyocyte. In this work, we performed a microarray to detect miRNAs in response to H2O2 treatment, and the results showed that miR-874 was substantially increased. We further studied the function of miR-874, and observed that knockdown of miR-874 attenuated necrosis in the cellular model and also MI in the animal model. We searched for the downstream mediator of miR-874 and identified that caspase-8 was a target of miR-874. Caspase-8 was able to antagonize necrosis. When suppressed by miR-874, caspase-8 lost the ability to repress necrotic program. In exploring the molecular mechanism by which miR-874 expression is regulated, we identified that Foxo3a could transcriptionally repress miR-874 expression. Foxo3a transgenic or knockout mice exhibited a low or high expression level of miR-874, and a reduced or enhanced necrosis and MI. Our present study reveals a novel myocardial necrotic regulating model, which is composed of Foxo3a, miR-874 and caspase-8. Modulation of their levels may provide a new approach for tackling myocardial necrosis. PMID:23828572

Acute Esophageal Necrosis: “Black Esophagus”

PubMed Central

Weigel, Tracey L.

2007-01-01

Acute esophageal necrosis (AEN) is an uncommon event. We report a case of an 84-year-old female with a giant paraesophageal hernia who presented with coffee ground emesis and on esophagogastroduodenoscopy (EGD) demonstrated findings consistent with acute esophageal necrosis and a giant paraesophageal hernia with normal-appearing gastric mucosa. She was managed conservatively with bowel rest, parenteral nutrition, and continuous intravenous proton pump inhibitor (PPI). After significant improvement in the gross appearance of her esophageal mucosa, surgery was performed to reduce her giant paraesophageal hernia. The patient's postoperative course was uneventful, and she was discharged home on postoperative day 6, tolerating a normal diet. The percutaneous endoscopic gastrostomy (PEG) tube was removed in clinic 2 months postoperatively. PMID:17651583

Lysosome-dependent necrosis specifically evoked in cancer cells by gold nanorods.

PubMed

Zhang, Fulei; Chen, Di; Wang, Ying; Zhang, Li; Dong, Wei; Dai, Jianxin; Jin, Chong; Dong, Xia; Sun, Yun; Zhao, He; Fan, Kexin; Liu, Hui; Chen, Bingdi; Zou, Hao; Li, Wei

2017-07-01

This article aims to explain the necrosis mechanisms of cancer cells specifically induced by gold nanorods (GNRs). The intracellular route and location of GNRs, the interaction between GNRs and lysosome, lysosome damage, cathepsin B release, necrosis complex formation, receptor-interacting protein 1 and TNF-α expression were systematically investigated. The GNRs with serum corona were internalized quickly by cancer cells and finally taken up by lysosomes. The GNRs damaged the lysosomal membrane, resulting in the leakage of cathepsin B, which promoted the activation of receptor-interacting protein 1 and necrosomes formation. Necrotic cells and their debris or ill cellular contents were engulfed by macrophages resulting in high-level release of TNF-α, which further confirmed necrosis. GNRs can specifically trigger lysosome-dependent necrosis in cancer cells.

Linking surface-fire behavior, stem heating, and tissue necrosis

Treesearch

A.S. Bova; M.B. Dickinson; M.B. Dickinson

2005-01-01

Data from 69 experimental, small-plot fires are used to describe relationships among fire intensity, barksurface heat flux, and depth of necrosis in stem tissue for red maple (Acer rubrum L.) and chestnut oak (Quercus prinus L.j. A tetrazolium staining technique was used to determine the depth of necrosis in tree boles subjected to fires with intensities of 20 to 2000...

(18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors.

PubMed

Toyonaga, Takuya; Hirata, Kenji; Yamaguchi, Shigeru; Hatanaka, Kanako C; Yuzawa, Sayaka; Manabe, Osamu; Kobayashi, Kentaro; Watanabe, Shiro; Shiga, Tohru; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Kuge, Yuji; Tamaki, Nagara

2016-07-01

Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Arthur K., E-mail: arthur.liu@ucdenver.ed; Macy, Margaret E.; Foreman, Nicholas K.

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 therapymore » 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.« less

Cirrhosis is a risk factor for total hip arthroplasty for avascular necrosis.

PubMed

Deleuran, Thomas; Overgaard, Søren; Vilstrup, Hendrik; Jepsen, Peter

2016-06-01

Background and purpose - There are limited data on risk factors for avascular necrosis of the hip, but cirrhosis has been proposed as a risk factor. We examined the association between cirrhosis and incidence of total hip arthroplasty for avascular necrosis. Methods - We used nationwide healthcare data to identify all Danish residents diagnosed with cirrhosis in 1994-2011, and matched them 1:5 by age and sex to non-cirrhotic reference individuals from the general population. We excluded people with a previous total hip arthroplasty, a previous hip fracture, or a previous diagnosis of avascular necrosis. We used stratified Cox regression to estimate the hazard ratio (HR) for cirrhosis patients relative to reference individuals, adjusting for potential confounders. We used the cumulative incidence function to compute 5-year risks. Results - We included 25,421 cirrhosis patients and 114,052 reference individuals. Their median age was 57 years, and 65% were men. 45 cirrhosis patients and 44 reference individuals underwent total hip arthroplasty for avascular necrosis. Cirrhosis patients' HR for a total hip arthroplasty for avascular necrosis was 10 (95% CI: 6-17), yet their 5-year risk of avascular necrosis was only 0.2%. For the reference individuals, the 5-year risk was 0.02%. Interpretation - Cirrhosis is a strong risk factor for avascular necrosis of the hip, but it is rare even in cirrhosis patients.

Cirrhosis is a risk factor for total hip arthroplasty for avascular necrosis

PubMed Central

Deleuran, Thomas; Overgaard, Søren; Vilstrup, Hendrik; Jepsen, Peter

2016-01-01

Background and purpose There are limited data on risk factors for avascular necrosis of the hip, but cirrhosis has been proposed as a risk factor. We examined the association between cirrhosis and incidence of total hip arthroplasty for avascular necrosis. Methods We used nationwide healthcare data to identify all Danish residents diagnosed with cirrhosis in 1994–2011, and matched them 1:5 by age and sex to non-cirrhotic reference individuals from the general population. We excluded people with a previous total hip arthroplasty, a previous hip fracture, or a previous diagnosis of avascular necrosis. We used stratified Cox regression to estimate the hazard ratio (HR) for cirrhosis patients relative to reference individuals, adjusting for potential confounders. We used the cumulative incidence function to compute 5-year risks. Results We included 25,421 cirrhosis patients and 114,052 reference individuals. Their median age was 57 years, and 65% were men. 45 cirrhosis patients and 44 reference individuals underwent total hip arthroplasty for avascular necrosis. Cirrhosis patients’ HR for a total hip arthroplasty for avascular necrosis was 10 (95% CI: 6–17), yet their 5-year risk of avascular necrosis was only 0.2%. For the reference individuals, the 5-year risk was 0.02%. Interpretation Cirrhosis is a strong risk factor for avascular necrosis of the hip, but it is rare even in cirrhosis patients. PMID:26900635

Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent.

PubMed

Zhang, Dongjian; Huang, Dejian; Ji, Yun; Jiang, Cuihua; Li, Yue; Gao, Meng; Yao, Nan; Liu, Xuejiao; Shao, Haibo; Jing, Su; Ni, Yicheng; Yin, Zhiqi; Zhang, Jian

2015-02-01

Necrosis-avid agents are a class of compounds that selectively accumulate in the necrotic tissues after systemic administration, which can be used for in vivo necrosis imaging and targeted therapies. In order to search for a necrosis-avid tracer agent with improved drugability, we labelled iodine-131 on sennoside B (SB) as a naturally occurring median dianthrone compound. The necrosis targetability and clearance properties of (131)I-SB were evaluated in model rats with liver and muscle necrosis. On SPECT/CT images, a "hot spot" in the infarcted liver lobe and necrotic muscle was persistently observed at 24 h and 72 h post-injection (p.i.). Gamma counting of the tissues of interest revealed a radioactivity ratio of necrotic to viable liver at 4.6 and 3.4 and of necrotic to viable muscle at 7.0 and 8.8 at 24 h and 72 h p.i., respectively. The good match of autoradiographs and fluoromicroscopic images with corresponding histochemical staining suggested preferential uptake of (131)I-SB in necrotic tissue. Pharmacokinetic study revealed that (131)I-SB has an elimination half-life of 8.6 h. This study indicates that (131)I-SB shows not only prominent necrosis avidity but also favourable pharmacokinetics, which may serve as a potential necrosis-avid diagnostic agent for assessment of tissue viability.

Fast Neutron Induced Autophagy Leads To Necrosis In Glioblastoma Multiforme Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yasui, Linda; Gladden, Samantha; Andorf, Christine

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 samplesmore » 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.« less

[Methods for evaluating diagnostic tests in Enfermedades Infecciosas y Microbiología Clínica].

PubMed

Ramos, J M; Hernández, I

1998-04-01

In the field of infectious diseases and clinical microbiology, the evaluation of diagnostic tests (DT) is an important research area. The specific difficulties of this type of research has motivated that have not caught the severity methodological of others areas of clinical research. This article try to asses and characterize the methodology of articles about DT published in Enfermedades Infecciosas y Microbiología Clínica (EIMC) journal. Forty-five articles was selected in the EIMC journal during the 1990-1996 period, because of determinate the sensitivity and specificity of different DT. Methodological standards, extensively accepted was used. In all of articles, except one (98%) the gold standard was specified yours use, however in 4 studies (9%) include the DT in the gold standard (incorporation bias). The correct description of DT was reported in 75% of cases, but only in 11% cases the reproducibility of test was evaluated. The description of source of reference population, standard of inclusion and spectrum of composition was described in 58, 33 and 40% of articles, respectively. In 33% of studies presented workup bias, only 6% commented blind-analysis of results, and 11% presented indeterminate test results. Half of the studies reported test indexes for clinical subgroups, only one article (2%) provided numerical precision for test indexes, and only 7% reported receiver operating characteristics curves. The methodological quality of DT research in the EIMC journal may improve in different aspects of design and presentation of results.

Preoperative imaging and prediction of oesophageal conduit necrosis after oesophagectomy for cancer.

PubMed

Lainas, P; Fuks, D; Gaujoux, S; Machroub, Z; Fregeville, A; Perniceni, T; Mal, F; Dousset, B; Gayet, B

2017-09-01

Oesophageal conduit necrosis following oesophagectomy is a rare but life-threatening complication. The present study aimed to assess the impact of coeliac axis stenosis on outcomes after oesophagectomy for cancer. The study included consecutive patients who had an Ivor Lewis procedure with curative intent for middle- and lower-third oesophageal cancer at two tertiary referral centres. All patients underwent preoperative multidetector CT with arterial phase to detect coeliac axis stenosis. The coeliac artery was classified as normal, with extrinsic stenosis due to a median arcuate ligament or with intrinsic stenosis caused by atherosclerosis. Some 481 patients underwent an Ivor Lewis procedure. Of these, ten (2·1 per cent) developed oesophageal conduit necrosis after surgery. Coeliac artery evaluation revealed a completely normal artery in 431 patients (91·5 per cent) in the group without conduit necrosis and in one (10 per cent) with necrosis (P < 0·001). Extrinsic stenosis of the coeliac artery due to a median arcuate ligament was found in two patients (0·4 per cent) without conduit necrosis and five (50 per cent) with necrosis (P < 0·001). Intrinsic stenosis of the coeliac artery was found in 11 (2·3 per cent) and eight (80 per cent) patients respectively (P < 0·001). Eight patients without (1·7 per cent) and five (50 per cent) with conduit necrosis had a single and thin left gastric artery (P < 0·001). This study suggests that oesophageal conduit necrosis after oesophagectomy for cancer may be due to pre-existing coeliac axis stenosis. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Focal necrosis mimicking breast cancer following coronary bypass grafting.

PubMed

Coufal, Oldřich; Ostřížek, Tomáš; Krsička, Petr; Lžičařová, Eva; Nenutil, Rudolf; Procházková, Monika; Bencsiková, Beatrix; Grell, Peter; Šefr, Roman

2017-05-30

Breast cancer can be diagnosed easily in most cases. However, occasionally, we are faced with some conditions that can mimic it. These may include inflammations, benign tumors, cysts, hematomas, or, more rarely, focal necrosis. This report presents a case of focal breast necrosis following myocardial revascularization with the left internal mammary artery, which is a very rare condition, with only few cases described in the literature. The necrosis becomes usually apparent a few days or weeks after the surgery and is often coincidental with the dehiscence of sternotomy with necrosis of wound edges. As it mostly affects the skin, it can be easily recognized. Also, our patient developed a dehisced sternotomy shortly after the surgery but there were no obvious objective changes on the breast. The condition was first dominated only by non-specific subjective symptom-pain. Later, a lump in the breast occurred, when the sternotomy had already healed. Moreover, an enlarged lymph node was palpable in the axilla. Because of non-typical symptoms, the condition was suggestive of breast cancer for a relatively long time. The patient had suffered from a very strong pain until she was treated by mastectomy with a good clinical result. Mammary necrosis following the coronary artery bypass is rare. In most cases, it manifests on the skin shortly after the surgery concurrently with dehisced sternotomy, so it can be easily diagnosed. However, in sporadic cases, the symptoms may occur later and may mimic breast cancer. Our objective is to raise awareness of this rare condition.

Morphometric findings in avascular necrosis of the femoral head.

PubMed

Kamal, Diana; Trăistaru, Rodica; Alexandru, D O; Kamal, C K; Pirici, D; Pop, O T; Mălăescu, D Gh

2012-01-01

Avascular necrosis of the femoral head is an illness with a controversial etiology, the trigger event being the suppression of blood flow to the femoral head. The disease affects mostly young adults within their third and fifth decade, the majority of the patients being men. The main risk factors are trauma, chronic alcohol consumption, smoking, corticotherapy. The main goal of our study is to describe the morphometric changes found in the bone tissue of patients diagnosed with avascular necrosis of the femoral head, with different risk factors, by comparing the area of bone trabeculae inside the area of necrosis with that from the adjacent viable tissue. The morphometric study used biological material from 16 patients with ages between 29 and 57 years, who underwent surgery for avascular necrosis of the femoral head. They were admitted in the Orthopedics Department at the Emergency County Hospital in Craiova between 2010 and 2011 and were split into four groups. Group I presented trauma as the main risk factor, Group II had corticotherapy as the defining risk factor, Group III presented chronic alcohol consumption and Group IV was represented by the patients who smoked and exhibited chronic alcohol consumption. There was not a significant statistical difference between the areas of bone trabeculae of the four groups when we compared viable bone tissue to the necrotized one. Knowing the risk factors of the avascular necrosis of the femoral head is critical to the management of the disease, because diagnosing it in an early stage is a necessity for obtaining a good result for conservative treatment.

Bcl-xL mediates RIPK3-dependent necrosis in M. tuberculosis-infected macrophages

PubMed Central

Zhao, Xiaomin; Khan, Nargis; Gan, Huixian; Tzelepis, Fanny; Nishimura, Tomoyasu; Park, Seung-Yeol; Divangahi, Maziar; Remold, Heinz G.

2017-01-01

Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mφ, which is essential for successful pathogenesis. Here we demonstrate that necrosis of Mtb-infected Mφ is dependent on the action of the cytosolic kinase Receptor Interacting Protein 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma - extra large (Bcl-xL). RIPK3-deficient Mφ are able to better control bacterial growth in vitro and in vivo. Cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-xL. Furthermore, necrosis is associated with stabilization of hexokinase II on the mitochondria as well as cyclophilin D-dependent mitochondrial permeability transition (MPT). These events up-regulate the level of reactive oxygen species (ROS) to induce necrosis. Thus, in Mtb-infected Mφ mitochondria are an essential platform for induction of necrosis by activating RIPK3 function and preventing caspase 8 - activation. PMID:28401933

Bcl-xL mediates RIPK3-dependent necrosis in M. tuberculosis-infected macrophages.

PubMed

Zhao, X; Khan, N; Gan, H; Tzelepis, F; Nishimura, T; Park, S-Y; Divangahi, M; Remold, H G

2017-11-01

Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mϕ, which is essential for successful pathogenesis in tuberculosis. Here we demonstrate that necrosis of Mtb-infected Mϕ is dependent on the action of the cytosolic Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma-extra large (Bcl-x L ). RIPK3-deficient Mϕ are able to better control bacterial growth in vitro and in vivo. Mechanistically, cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-x L . Furthermore, necrosis is associated with stabilization of hexokinase II on the mitochondria as well as cyclophilin D-dependent mitochondrial permeability transition. Collectively, these events upregulate the level of reactive oxygen species to induce necrosis. Thus, in Mtb-infected Mϕ, mitochondria are an essential platform for induction of necrosis by activating RIPK3 function and preventing caspase 8-activation.

Risk factors associated with intestinal necrosis in children with failed non-surgical reduction for intussusception.

PubMed

Huang, Hui-Ya; Huang, Xiao-Zhong; Han, Yi-Jiang; Zhu, Li-Bin; Huang, Kai-Yu; Lin, Jing; Li, Zhong-Rong

2017-05-01

Intestinal necrosis is the most serious complication of intussusception. The risk factors associated with intestinal necrosis in pediatric patients with intussusception have not been well characterized. This study aimed to investigate the risk factors associated with intestinal necrosis in pediatric patients with failed non-surgical reduction for intussusception. Hospitalized patients who failed the air-enema reduction for intussusception in the outpatient department and subsequently underwent surgery were retrospectively reviewed. All cases were categorized into two groups: intestinal necrosis group and non-intestinal necrosis group based on the surgical findings. Demographic and clinical features including the findings from the surgery were recorded and analyzed. Factors associated with intestinal necrosis were analyzed using univariate and multivariate unconditional logistic regression analyses. A total of 728 cases were included. Among them, 171 had intestinal necrosis at the time of surgery. The group with intestinal necrosis had a longer duration of symptom or length of illness (P = 0.000), and younger (P = 0.000) than the non-intestinal necrosis group. Complex/compound type of intussusceptions is more likely to have intestinal necrosis. Multivariate analysis showed that the presence of grossly bloody stool (OR = 2.12; 95% CI 1.19-3.76, P = 0.010) and duration of symptom (OR = 1.07; 95% CI 1.06-1.08, P = 0.000) were independent risk factors for intestinal necrosis in patients hospitalized for surgical reduction for intussusceptions. At time of admission, the presence of bloody stools and duration of symptom are the important risk factors for developing intestinal necrosis for those patients who failed non-surgical reduction. The length of illness has the highest sensitivity and specificity to correlate with intestinal necrosis. This finding may suggest that we should take the intussusception cases that have the longer duration of

Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, Samuel T., E-mail: chaos@ccf.org; Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, Ohio; Ahluwalia, Manmeet S.

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 diagnosismore » and treatment of radiation necrosis.« less

Avascular necrosis of the femoral head presenting as trochanteric bursitis.

PubMed Central

Mandell, B F

1990-01-01

Five patients are described with avascular necrosis of the femoral head who presented with ipsilateral trochanteric bursitis, in the absence of clearcut hip joint disease. Avascular necrosis was indicated by magnetic resonance imaging. It is suggested that clinical trochanteric bursitis, especially when refractory to local corticosteroid treatment, may be the initial sign of hip disease. In the patient with risk factor(s) for avascular necrosis that diagnosis should be considered and evaluated with appropriate studies, such as magnetic resonance imaging, to prevent weight bearing at an early stage and permit possible surgical decompression in the hope of postponing or obviating the need for total hip replacement. PMID:2241294

Previously reported sonographic appearances of regional melanoma metastases are not likely due to necrosis.

PubMed

Catalano, Orlando; Voit, Christiane; Sandomenico, Fabio; Mandato, Ylenia; Petrillo, Mario; Franco, Renato; Botti, Gerardo; Caracò, Corrado; Mozzillo, Nicola; D'Errico, Adolfo Gallipoli

2011-08-01

Sonography has proven to be a reliable tool in early detection of lymph node and in-transit cutaneous-subcutaneous metastases. Those metastases normally appear as hypoechoic or even anechoic lesions on sonography. It has been assumed that this appearance is due to necrosis of the lesions, but so far, that assumption has never been proven. The purpose of this retrospective study was to evaluate whether the hypoechoic appearance of melanoma metastasis is really due to tumor necrosis. From a radiographic database, we retrieved 212 melanoma cases imaged with sonography over a 2-year period for disease staging or follow-up. We selected 37 positive cases with 84 nodal and extranodal (satellite and in-transit) metastatic lesions and reviewed the sonograms and pathologic slides (slides available for 40 of 84 lesions). We retrospectively assessed the vascularization pattern (color Doppler images available for 78 of 84 lesions), categorizing it as poor, intermediate, or consistent. We also looked for necrosis on the histopathologic material, categorizing it into scores of 0, 1, 2, and 3 for absence of necrosis, less than 20% necrosis, 20% to 40% necrosis, and greater than 40% necrosis, respectively. Despite their gray scale appearance, most melanoma lesions were vascularized on color Doppler imaging and showed limited necrosis at histopathologic analysis. Consistent vascularization on Doppler imaging, excluding substantial necrosis, was found in 44 of 78 lesions (56.4%). Poor vascularization on Doppler imaging, suggesting necrosis, was present in only 14% of the lesions. Substantial necrosis (scores of 2 and 3) was found pathologically in only 10% of the lesions. Necrosis seems to be an uncommon event in melanoma metastasis and is probably not the basis for its low-level echo pattern on sonography. The hypoechoic appearance is very typical of melanoma metastasis and is likely due to massive melanomatous infiltration (with the poor echo reflectivity of melanin). However

Avascular necrosis of the femoral head after osteosynthesis of femoral neck fracture.

PubMed

Min, Byung-Woo; Kim, Sung-Jin

2011-05-18

The reported incidence of avascular necrosis after femoral neck fracture fixation varies widely, and there is no consensus regarding its risk factors. We evaluated the incidence of avascular necrosis of the femoral head with the use of contemporary techniques for femoral neck fracture fixation. We then sought to determine what potential risk factors influenced the development of avascular necrosis.Between 1990 and 2005, one hundred sixty-three intracapsular femoral neck fractures in 163 patients were treated with internal fixation at our level-I trauma center. All patients were monitored until conversion to total hip arthroplasty or for a minimum of 2 years postoperatively. Ten patients (10 hips) died and 7 patients (7 hips) were lost to follow-up. The remaining 146 patients (146 hips) had a mean 5.2 years of follow-up (range, 3 months to 17 years). The incidence of avascular necrosis was 25.3% (37 hips). The average time to diagnosis of avascular necrosis was 18.8 months (range, 3-47 months). Patient sex, age, interval from injury to surgery, and mechanism of injury were statistically not associated with the development of avascular necrosis. The quality of fracture reduction, adequacy of fixation, degree of displacement, and comminution of the posterior cortex were significantly associated. After we controlled for patient and radiographic characteristics, multivariate analyses indicated that the important predictors for avascular necrosis are poor reduction (odds ratio=13.889) and initial displacement of the fracture (odds ratio=4.693). Copyright 2011, SLACK Incorporated.

Conservative management of distal leg necrosis in lung transplant recipients.

PubMed

Aigner, F; Husmann, M; Huber, L C; Benden, C; Schuurmans, M M

2017-05-01

Critical limb ischemia (CLI) with distal leg necrosis in lung transplant recipients (LTR) is associated with a high risk for systemic infection and sepsis. Optimal management of CLI has not been defined so far in LTR. In immunocompetent individuals with leg necrosis, surgical amputation would be indicated and standard care. We report on the outcome of four conservatively managed LTR with distal leg necrosis due to peripheral arterial disease (PAD) with medial calcification of the distal limb vessels. Time interval from lung transplantation to CLI ranged from four years (n = 1) to more than a decade (n = 3). In all cases a multimodal therapy with heparin, acetylsalicylic acid, iloprost and antibiotic therapy was performed, in addition to a trial of catheter-based revascularization. Surgical amputation of necrosis was not undertaken due to fear of wound healing difficulties under long-term immunosuppression and impaired tissue perfusion. Intensive wound care and selective debridement were performed. Two patients developed progressive gangrene followed by auto-amputation during a follow-up of 43 and 49 months with continued ambulation and two patients died of unrelated causes 9 and 12 months after diagnosis of CLI. In conclusion, we report a conservative treatment strategy for distal leg necrosis in LTR without surgical amputation and recommend this approach based on our experience. Copyright © 2017 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Femoral Head Avascular Necrosis Is Not Caused by Arthroscopic Posterolateral Femoroplasty.

PubMed

Rupp, Robert E; Rupp, Sasha N

2016-05-01

This study was conducted to identify the risk of avascular necrosis of the femoral head after arthroscopic femoroplasty extending to the posterolateral femoral neck, the source of the primary blood supply to the femoral head. Cam lesions of femoroacetabular impingement are typically anterior along the junction of the femoral head and neck. However, anatomic variations can involve the posterolateral vascular region of the femoral head and neck. Femoroplasty involving this vascular region can lead to injury to the blood supply to the femoral head, with subsequent avascular necrosis. If the posterolateral portion of the cam lesion is preserved, persistent femoroacetabular impingement may occur. A retrospective review identified 112 patients who underwent arthroscopic femoroplasty for femoroacetabular impingement over a 2-year period. Of these patients, 14 had femoroplasty that extended to the posterolateral femoral head. Of this group, 5 had undergone magnetic resonance imaging (MRI) after femoroplasty and the other 9 were contacted to undergo MRI of the hip to evaluate for avascular necrosis. A radiologist and the senior author evaluated all MRI scans specifically for avascular necrosis of the femoral head. All procedures were performed by the senior author. Mean age of the 14 patients (8 women and 6 men) with femoroplasty that extended into the posterolateral vascular region of the femoral head was 44 years (range, 23-69 years). All 14 patients underwent MRI evaluation of the affected hip a mean of 25 months (range, 7-44 months) after femoroplasty. No MRI scans showed evidence of avascular necrosis of the femoral head. Femoroplasty of the posterolateral vascular region of the femoral head is not associated with avascular necrosis. Patients with femoroacetabular impingement and a cam lesion extending to the posterolateral femoral head can undergo femoroplasty of this region without the development of avascular necrosis. [Orthopedics. 2016; 39(3):177-180.]. Copyright

Dose-dependent effects of alpha-naphthylisothiocyanate disconnect biliary fibrosis from hepatocellular necrosis.

PubMed

Joshi, Nikita; Ray, Jessica L; Kopec, Anna K; Luyendyk, James P

2017-01-01

Exposure of rodents to the xenobiotic α-naphthylisothiocyanate (ANIT) is an established model of experimental intrahepatic bile duct injury. Administration of ANIT to mice causes neutrophil-mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT-induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0.05%, 0.1%), on the severity of various liver pathologies in a model of chronic ANIT exposure. ANIT-elicited increases in liver inflammation and hepatocellular necrosis increased with dose. Remarkably, there was no connection between increased hepatocellular necrosis and bile duct hyperplasia and peribiliary fibrosis, as these pathologies increased similarly in mice exposed to either dose of ANIT. The results indicate that the severity of hepatocellular necrosis does not dictate the extent of bile duct hyperplasia/fibrosis in ANIT-exposed mice. © 2016 Wiley Periodicals, Inc.

Dose-Dependent Effects of Alpha-Naphthylisothiocyanate Disconnect Biliary Fibrosis from Hepatocellular Necrosis

PubMed Central

Joshi, Nikita; Ray, Jessica L.; Kopec, Anna K.; Luyendyk, James P.

2017-01-01

Exposure of rodents to the xenobiotic α-naphthylisothiocyanate (ANIT) is an established model of experimental intrahepatic bile duct injury. Administration of ANIT to mice causes neutrophil-mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT-induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well-characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0.05%, 0.1%), on the severity of various liver pathologies in a model of chronic ANIT exposure. ANIT-elicited increases in liver inflammation and hepatocellular necrosis increased with dose. Remarkably, there was no connection between increased hepatocellular necrosis and bile duct hyperplasia and peribiliary fibrosis, as these pathologies increased similarly in mice exposed to either dose of ANIT. The results indicate that the severity of hepatocellular necrosis does not dictate the extent of bile duct hyperplasia/fibrosis in ANIT-exposed mice. PMID:27605088

Inhibition of Prostaglandin D Synthase Suppresses Muscular Necrosis

PubMed Central

Mohri, Ikuko; Aritake, Kosuke; Taniguchi, Hidetoshi; Sato, Yo; Kamauchi, Shinya; Nagata, Nanae; Maruyama, Toshihiko; Taniike, Masako; Urade, Yoshihiro

2009-01-01

Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor β1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy. PMID:19359520

[Uterine necrosis after arterial embolization for postpartum hemorrhage].

PubMed

Belghiti, J; Tassin, M; Raiffort, C; Zappa, M; Poujade, O; Bout, H; Mandelbrot, L

2014-02-01

Radiologic embolization of the uterine arteries is increasingly used to treat severe postpartum hemorrhage, as an alternative to surgical procedures. Guidelines have been published in order to standardize the indications as well as the technique. An important objective was to limit severe complications such as uterine necrosis. We report a case of a uterine necrosis after arterial embolization for severe postpartum hemorrhage due to uterine atony on a uterus with fibroids. This complication occurred despite the use of the recommended technique. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Phencyclidine-induced malignant hyperthermia causing submassive liver necrosis.

PubMed

Armen, R; Kanel, G; Reynolds, T

1984-07-01

This report describes three male patients arrested for aggressive and combative behavior, characteristic of phencyclidine intoxication, in whom severe hyperthermia, respiratory failure, and coma developed. Two days after the malignant hyperthermic event, serum transaminase levels rose acutely to extremely high levels with concomitant elevations in bilirubin levels and a fall in prothrombin activity. Liver biopsy specimens in two patients showed marked perivenular necrosis and collapse. No specific treatment was directed at the phencyclidine intoxication. Two of the three patients survived. Submassive liver necrosis caused by malignant hyperthermia is an unusual complication of phencyclidine abuse.

Gastric necrosis and perforation in a patient with Asperger's syndrome.

PubMed

Hicks, Georgina; D'Souza, Nigel; Thomas, Rhys; Brar, Ranjeet

2017-09-27

Acute gastric necrosis is a very rare but potentially fatal condition which has been reported in patients with abnormal eating behaviours.We describe the case of a 24-year-old female with a background of Asperger's syndrome, who presented with abdominal pain and gross distension. She underwent an emergency exploratory laparotomy and was found to have a massively distended, necrotic stomach. A total gastrectomy was performed with interval reconstruction planned. This case reports the surgical management of a rarely seen condition and highlights the importance of recognising gastric necrosis and its causes, which include patients with abnormal eating behaviours, the majority of whom are young females. This is the first report highlighting gastric necrosis in a patient with Asperger's syndrome and coincides with a growing recognition of the association between eating disorders and the autistic spectrum. It is also a rare example of patient survival following total gastric necrosis with perforation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

TAK1 kinase switches cell fate from apoptosis to necrosis following TNF stimulation.

PubMed

Morioka, Sho; Broglie, Peter; Omori, Emily; Ikeda, Yuka; Takaesu, Giichi; Matsumoto, Kunihiro; Ninomiya-Tsuji, Jun

2014-02-17

TNF activates three distinct intracellular signaling cascades leading to cell survival, caspase-8-mediated apoptosis, or receptor interacting protein kinase 3 (RIPK3)-dependent necrosis, also called necroptosis. Depending on the cellular context, one of these pathways is activated upon TNF challenge. When caspase-8 is activated, it drives the apoptosis cascade and blocks RIPK3-dependent necrosis. Here we report the biological event switching to activate necrosis over apoptosis. TAK1 kinase is normally transiently activated upon TNF stimulation. We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation. In addition, we also demonstrated that activation of RIPK1 and RIPK3 promoted TAK1 activation, suggesting a positive feedforward loop of RIPK1, RIPK3, and TAK1. Conversely, ablation of TAK1 caused caspase-dependent apoptosis, in which Ripk3 deletion did not block cell death either in vivo or in vitro. Our results reveal that TAK1 activation drives RIPK3-dependent necrosis and inhibits apoptosis. TAK1 acts as a switch between apoptosis and necrosis.

[Bilateral acute retinal necrosis in a patient with acquired immunodeficiency syndrome].

PubMed

Menerath, J M; Gerard, M; Laurichesse, H; Goldschmidt, P; Peigue-Lafeuille, H; Rozenberg, F; Beytout, J

1995-01-01

A case of bilateral progressive outer retinal necrosis occurred after herpes zoster ophthalmicus in a patient with acquired immunodeficiency syndrome. This case does not correspond to the classical picture of progressive outer retinal necrosis. The disease led to blindness despite intravenous therapy with acyclovir and foscarnet. PCR could not identify any virus in the aqueous humour, but VZV is evidenced in cerebrospinal fluid. Acute retinal necrosis is now clearly defined by the American Uveitis Society, which should allow to determine its incidence and risk factors. Herpes zoster usually precedes the acute outer retinal necrosis. The infectious theory (VZV, HSV, CMV) widely prevails over the immune theory. We prefer the virus genome identification in the aqueous humor or in the vitreous by PCR to confirm diagnosis rather than the specific antibody titration. Therapy consists in acyclovir, foscarnet and ganciclovir. But whatever the treatment, the visual prognosis is poor.

Computed tomography predictors of hepatocellular carcinoma tumour necrosis after chemoembolization

PubMed Central

Bryant, Mary K; Dorn, David P; Zarzour, Jessica; Smith, J Kevin; Redden, David T; Saddekni, Souheil; Aal, Ahmed Kamel Abdel; Gray, Stephen H; Eckhoff, Devin E; DuBay, Derek A

2014-01-01

Background Radiographical features associated with a favourable response to trans-arterial chemoembolization (TACE) are poorly defined for patients with hepatocellular carcinoma (HCC). Methods From 2008 to 2012, all first TACE interventions for HCC performed at the University of Alabama at Birmingham (UAB) were retrospectively reviewed. Only patients with a pre-TACE and a post-TACE computed tomography (CT) scan were included in the analyses (n = 115). HCC tumour response to TACE was quantified via the the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Univariate and multivariable analyses were constructed. Results The index HCC tumours experienced a > 90% or complete tumour necrosis in 59/115 (51%) of patients after the first TACE intervention. On univariate analysis, smaller tumour size, peripheral tumour location and arterial enhancement were associated with a > 90% or complete tumour necrosis, whereas, only smaller tumour size [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.48, 0.81] and peripheral location (OR 6.91; 95% CI 1.75, 27.29) were significant on multivariable analysis. There was a trend towards improved survival in the patients that experienced a > 90% or complete tumour necrosis (P = 0.08). Conclusions Peripherally located smaller HCC tumours are most likely to experience a > 90% or complete tumour necrosis after TACE. Surprisingly, arterial-phase enhancement and portal venous-phase washout were not significantly predictive of TACE-induced tumour necrosis. The TACE response was not statistically associated with improved survival. PMID:23980917

Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging.

PubMed

Stammes, Marieke A; Knol-Blankevoort, Vicky T; Cruz, Luis J; Feitsma, Hans R I J; Mezzanotte, Laura; Cordfunke, Robert A; Sinisi, Riccardo; Dubikovskaya, Elena A; Maeda, Azusa; DaCosta, Ralph S; Bierau, Katja; Chan, Alan; Kaijzel, Eric L; Snoeks, Thomas J A; van Beek, Ermond R; Löwik, Clemens W G M

2016-12-01

Recently we showed that a number of carboxylated near-infrared fluorescent (NIRF) cyanine dyes possess strong necrosis avid properties in vitro as well as in different mouse models of spontaneous and therapy-induced tumor necrosis, indicating their potential use for cancer diagnostic- and prognostic purposes. In the previous study, the detection of the cyanines was achieved by whole body optical imaging, a technique that, due to the limited penetration of near-infrared light, is not suitable for investigations deeper than 1 cm within the human body. Therefore, in order to facilitate clinical translation, the purpose of the present study was to generate a necrosis avid cyanine-based NIRF probe that could also be used for single photon emission computed tomography (SPECT). For this, the necrosis avid NIRF cyanine HQ4 was radiolabeled with 111 indium, via the chelate diethylene triamine pentaacetic acid (DTPA). The necrosis avid properties of the radiotracer [ 111 In]DTPA-HQ4 were examined in vitro and in vivo in different breast tumor models in mice using SPECT and optical imaging. Moreover, biodistribution studies were performed to examine the pharmacokinetics of the probe in vivo. Using optical imaging and radioactivity measurements, in vitro, we showed selective accumulation of [ 111 In]DTPA-HQ4 in dead cells. Using SPECT and in biodistribution studies, the necrosis avidity of the radiotracer was confirmed in a 4T1 mouse breast cancer model of spontaneous tumor necrosis and in a MCF-7 human breast cancer model of chemotherapy-induced tumor necrosis. The radiotracer [ 111 In]DTPA-HQ4 possessed strong and selective necrosis avidity in vitro and in various mouse models of tumor necrosis in vivo, indicating its potential to be clinically applied for diagnostic purposes and to monitor anti-cancer treatment efficacy.

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn; National Institute of Biological Sciences, Beijing 102206; Jin, Wei

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. Inhibitionmore » of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.« less

Macroscopic and microscopic findings in avascular necrosis of the femoral head.

PubMed

Kamal, Diana; Alexandru, D O; Kamal, C K; Streba, C T; Grecu, D; Mogoantă, L

2012-01-01

The avascular necrosis of the femoral head is an illness induced by the cutoff of blood flow to the femoral head and it affects mostly young adults between the ages of 30 and 50 years, raising therapeutic and diagnostic issues. Many risk factors are incriminated in the development of avascular necrosis of the femoral head like: trauma, chronic alcohol consumption, smoking, administration of corticosteroid drugs, most of the cases are considered to be idiopathic. The main goal of our paper is to describe the macroscopic and microscopic variations of the bone structure, which occur in patients with avascular necrosis of the femoral head. The biological material needed for our study was obtained following hip arthroplasty surgery in 26 patients between the ages of 29 and 59 years, which previously were diagnosed with avascular necrosis of the femoral head and admitted in the Orthopedics Department of the Emergency County Hospital of Craiova (Romania) between 2010 and 2011. From a macroscopic point of view, we found well defined areas of necrosis, most of which were neatly demarcated of the adjacent viable tissue by hyperemic areas, loss of shape and contour of the femoral head and transformations of the articular cartilage above the area of necrosis. When examined under the microscope, we found vast areas of fibrosis, narrow bone trabeculae, obstructed blood vessels or blood vessels with clots inside, hypertrophic fat cells, bone sequestration but also small cells and pyknotic nuclei. The microscopic and macroscopic findings on the femoral head sections varied with the patients and the stage of the disease.

Tumor necrosis factor-alpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter.

PubMed

Shinohara, Mayuka; Sumino, Yasuhiro; Sato, Fuminori; Kiyono, Tohru; Hashimoto, Naohiro; Mimata, Hiromitsu

2017-06-01

To examine the inhibitory effects of tumor necrosis factor-α on myogenic differentiation of human urethral rhabdosphincter cells. A rhabdosphincter sample was obtained from a patient who underwent total cystectomy. To expand the lifespan of the primary cultured cells, rhabdosphincter myogenic cells were immortalized with mutated cyclin-dependent kinase 4, cyclin D1 and telomerase. The differential potential of the cells was investigated. The transfected human rhabdosphincter cells were induced for myogenic differentiation with recombinant human tumor necrosis factor-α and/or the tumor necrosis factor-α antagonist etanercept at different concentrations, and activation of signaling pathways was monitored. Human rhabdosphincter cells were selectively cultured for at least 40 passages. Molecular analysis confirmed the expression of myosin heavy chain, which is a specific marker of differentiated muscle cells, significantly increased after differentiation induction. Although tumor necrosis factor-α treatment reduced the myosin heavy chain expression in a concentration-dependent manner, etanercept inhibited this suppression. Tumor necrosis factor-α suppressed phosphorylation of protein kinase B and p38, whereas etanercept pretreatment promoted phosphorylation and myosin heavy chain expression in a concentration-dependent manner. Tumor necrosis factor-α inhibits differentiation of urethral rhabdosphincter cells in part through the p38 mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. Inhibition of tumor necrosis factor-α might be a useful strategy to treat stress urinary incontinence. © 2017 The Japanese Urological Association.

Novel drug discovery strategies for atherosclerosis that target necrosis and necroptosis.

PubMed

Coornaert, Isabelle; Hofmans, Sam; Devisscher, Lars; Augustyns, Koen; Van Der Veken, Pieter; De Meyer, Guido R Y; Martinet, Wim

2018-06-01

Formation and enlargement of a necrotic core play a pivotal role in atherogenesis. Since the discovery of necroptosis, which is a regulated form of necrosis, prevention of necrotic cell death has become an attractive therapeutic goal to reduce plaque formation. Areas covered: This review highlights the triggers and consequences of (unregulated) necrosis and necroptosis in atherosclerosis. The authors discuss different pharmacological strategies to inhibit necrotic cell death in advanced atherosclerotic plaques. Expert opinion: Addition of a necrosis or necroptosis inhibitor to standard statin therapy could be a promising strategy for primary prevention of cardiovascular disease. However, a necrosis inhibitor cannot block all necrosis stimuli in atherosclerotic plaques. A necroptosis inhibitor could be more effective, because necroptosis is mediated by specific proteins, termed receptor-interacting serine/threonine-protein kinases (RIPK) and mixed lineage kinase domain-like pseudokinase (MLKL). Currently, only RIPK1 inhibitors have been successfully used in atherosclerotic mouse models to inhibit necroptosis. However, because RIPK1 is involved in both necroptosis and apoptosis, and also RIPK1-independent necroptosis can occur, we feel that targeting RIPK3 and MLKL could be a more attractive therapeutic approach to inhibit necroptosis. Therefore, future challenges will consist of developing RIPK3 and MLKL inhibitors applicable in both preclinical and clinical settings.

A novel role for the apoptosis inhibitor ARC in suppressing TNFα-induced regulated necrosis

PubMed Central

Kung, G; Dai, P; Deng, L; Kitsis, R N

2014-01-01

TNFα signaling can promote apoptosis or a regulated form of necrosis. ARC (apoptosis repressor with CARD (caspase recruitment domain)) is an endogenous inhibitor of apoptosis that antagonizes both the extrinsic (death receptor) and intrinsic (mitochondrial/ER) apoptosis pathways. We discovered that ARC blocks not only apoptosis but also necrosis. TNFα-induced necrosis was abrogated by overexpression of wild-type ARC but not by a CARD mutant that is also defective for inhibition of apoptosis. Conversely, knockdown of ARC exacerbated TNFα-induced necrosis, an effect that was rescued by reconstitution with wild-type, but not CARD-defective, ARC. Similarly, depletion of ARC in vivo exacerbated necrosis caused by infection with vaccinia virus, which elicits severe tissue damage through this pathway, and sensitized mice to TNFα-induced systemic inflammatory response syndrome. The mechanism underlying these effects is an interaction of ARC with TNF receptor 1 that interferes with recruitment of RIP1, a critical mediator of TNFα-induced regulated necrosis. These findings extend the role of ARC from an apoptosis inhibitor to a regulator of the TNFα pathway and an inhibitor of TNFα-mediated regulated necrosis. PMID:24440909

Fulminant bilateral acute retinal necrosis after chickenpox - a case report.

PubMed

Dascalu, Ana Maria; Stana, Daniela; Popa-Cherecheanu, Alina; Popa-Cherecheanu, Matei; Serban, Dragos

2016-01-01

We present the case of a 34-year-old male, admitted for progressive bilateral loss of vision after a recent episode of chickenpox. Ophthalmological exam revealed bilateral acute retinal necrosis. As the patient was following a drug detoxification program, he was tested for HIV, HVB, HVC, and results highly positive. Immediate intravenous therapy with high doses of acyclovir and methylprednisolone was initiated, but the evolution was extremely severe resulting in necrotic retinal detachment. Surgery was performed in right eye, but no improvement of visual acuity was observed. The fulminant evolution of bilateral acute retinal necrosis and the lack of response to maximal intravenous therapy were clinical elements indicating coexistent immunosuppressive disease. Very severe acute retinal necrosis may occur in immunosuppressed patients, leading to blindness.

Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis.

PubMed

Garip, Gokhan; Sarandöl, Emre; Kaya, Ekrem

2013-11-28

To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP). One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated. There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P < 0.05 and 0.001 respectively) and in patients having pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P < 0.001). All of the patients in the necrosectomy group had endocrine dysfunction. Patients with SAP, NAP, pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

Diagnostic imaging in uterine incisional necrosis/dehiscence complicating cesarean section.

PubMed

Rivlin, Michel E; Patel, Rameshkumar B; Carroll, C Shannon; Morrison, John C

2005-12-01

To review the diagnostic imaging studies in patients with surgically proven uterine incisional necrosis/dehiscence complicating cesarean section and to compare these studies with the findings at surgery. Over a 6-year period, the records of 7 patients with imaging studies prior to surgery for uterine incisional necrosis/dehiscence complicating cesarean delivery were reviewed and compared with the findings at surgery. Four cases underwent computed tomography (CT) and sonography, 1 underwent CT only, and 2 underwent sonography only. Abnormal findings included abdominal free fluid in 4, pleural effusions in 3, dilated bowel in 3, possible bladder flap hematoma in 2 and single instances of liver abscess and retained products of conception. In no cases were all the studies normal, and necrosis/dehiscence was not demonstrated in any patient. Abdominal free fluid, bowel distension, pleural effusion and bladder flap hematoma seen on CT or sonogram in the postcesarean context suggest the possibility of uterine incisional necrosis/dehiscence. Magnetic resonance imaging (MRI) might then be indicated since MRI may be superior to CT in evaluating complications at the incisional site because of its multiplanar capability and greater degree of soft tissue contrast.

Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients.

PubMed

Senturk Ciftci, Hayriye; Demir, Erol; Savran Karadeniz, Meltem; Tefik, Tzevat; Yazici, Halil; Nane, Ismet; Savran Oguz, Fatma; Aydin, Filiz; Turkmen, Aydin

2017-12-18

Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P < .001) and at months 1 (8.0 ± 1.7 vs 11.8 ± 2.4; P < .001), 3 (7.7 ± 1.6 vs 9.6 ± 1.7; P = .002), and 6 (7.4 ± 1.6 vs 8.9 ± 0.9; P = .005). Our preliminary findings suggest that tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.

Apoptosis and Necrosis in the Liver

PubMed Central

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

2013-01-01

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

Apoptosis and necrosis in the liver.

PubMed

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L; Gores, Gregory J

2013-04-01

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of "programmed" necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article.

Human-Specific Bacterial Pore-Forming Toxins Induce Programmed Necrosis in Erythrocytes

PubMed Central

LaRocca, Timothy J.; Stivison, Elizabeth A.; Hod, Eldad A.; Spitalnik, Steven L.; Cowan, Peter J.; Randis, Tara M.

2014-01-01

ABSTRACT A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis. PMID:25161188

Predictors of Postoperative Wound Necrosis Following Primary Wound Closure of Open Ankle Fractures.

PubMed

Ovaska, Mikko T; Madanat, Rami; Mäkinen, Tatu J

2016-04-01

Most open malleolar ankle fracture wounds can be closed primarily after meticulous debridement. However, the development of wound necrosis following operative treatment of open malleolar ankle fractures can have catastrophic consequences. The aim of this study was to identify risk factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures. A total of 137 patients with open malleolar ankle fractures were identified. The open fracture wound was primarily closed in 110 of 137 (80%) patients, and postoperative wound necrosis occurred in 18 (16%) of these patients. These patients were compared to the open fracture patients without wound necrosis. Twenty possible risk factors for the development of wound necrosis were studied with logistic regression analysis. The variables that were independently associated with an increased risk for postoperative wound necrosis included ASA class ≥2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery. Our study showed that ASA class ≥2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery were the most important factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures. The findings warrant a further study specifically comparing primary and delayed wound closure in patients with Gustilo grade III open malleolar ankle fractures and different ASA classes. Also, the role of pulsatile lavage should be re-evaluated. Level III, retrospective comparative series. © The Author(s) 2016.

Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma.

PubMed

Adams, Hugo J A; de Klerk, John M H; Fijnheer, Rob; Dubois, Stefan V; Nievelstein, Rutger A J; Kwee, Thomas C

2015-03-01

To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ=-0.042, P=0.765), categorized lactate dehydrogenase (LDH) ratio (ρ=0.201, P=0.156), extranodal disease in major organs (φ=-0.245, P=0.083), Ann Arbor stage III/IV disease (φ=-0.208, P=0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ=0.015, P=0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P=0.003) and overall survival (P=0.004). The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Using computed tomography to assist with diagnosis of avascular necrosis complicating chronic scaphoid nonunion.

PubMed

Smith, Michael L; Bain, Gregory I; Chabrel, Nick; Turner, Perry; Carter, Chris; Field, John

2009-01-01

The primary aim of our study was to investigate use of long axis computed tomography (CT) in predicting avascular necrosis of the proximal pole of the scaphoid and subsequent fracture nonunion after internal fixation. In addition, we describe a new technique of measuring the position of a scaphoid fracture and provide data on its reproducibility. Thirty-one patients operated on by the senior author for delayed union or nonunion of scaphoid fracture were included. Preoperative CT scans were independently assessed for increased radiodensity of the proximal pole, converging trabeculae, degree of deformity, comminution, and fracture position. Intraoperative biopsies of the proximal pole were obtained and histologically assessed for evidence of avascular necrosis. The radiologic variables were statistically compared with the histologic findings. The presence of avascular necrosis was also compared with postoperative union status, identified on longitudinal CT scans. Preoperative CT features that statistically correlated with histologic evidence of avascular necrosis were increased radiodensity of the proximal pole and the absence of any converging trabeculae between the fracture fragments. The radiologic changes of avascular necrosis and the histologic confirmation of avascular necrosis were associated with persistent nonunion. Preoperative longitudinal CT of scaphoid nonunion is of great value in identifying avascular necrosis and predicting subsequent fracture union. If avascular necrosis is suspected based on preoperative CT, management options include vascularized bone grafts and bone morphogenic protein for younger patients and limited wrist arthrodesis for older patients. Diagnostic II.

Pravastatin Protects Against Avascular Necrosis of Femoral Head via Autophagy.

PubMed

Liao, Yun; Zhang, Ping; Yuan, Bo; Li, Ling; Bao, Shisan

2018-01-01

Autophagy serves as a stress response and may contribute to the pathogenesis of avascular necrosis of the femoral head induced by steroids. Statins promote angiogenesis and ameliorate endothelial functions through apoptosis inhibition and necrosis of endothelial progenitor cells, however the process used by statins to modulate autophagy in avascular necrosis of the femoral head remains unclear. This manuscript determines whether pravastatin protects against dexamethasone-induced avascular necrosis of the femoral head by activating endothelial progenitor cell autophagy. Pravastatin was observed to enhance the autophagy activity in endothelial progenitor cells, specifically by upregulating LC3-II/Beclin-1 (autophagy related proteins), and autophagosome formation in vivo and in vitro . An autophagy inhibitor, 3-MA, reduced pravastatin protection in endothelial progenitor cells exposed to dexamethasone by attenuating pravastatin-induced autophagy. Adenosine monophosphate-activated protein kinase (AMPK) is a key autophagy regulator by sensing cellular energy changes, and indirectly suppressing activation of the mammalian target of rapamycin (mTOR). We found that phosphorylation of AMPK was upregulated however phosphorylation of mTOR was downregulated in pravastatin-treated endothelial progenitor cells, which was attenuated by AMPK inhibitor compound C. Furthermore, liver kinase B1 (a phosphorylase of AMPK) knockdown eliminated pravastatin regulated autophagy protein LC3-II in endothelial progenitor cells in vitro . We therefore demonstrated pravastatin rescued endothelial progenitor cells from dexamethasone-induced autophagy dysfunction through the AMPK-mTOR signaling pathway in a liver kinase B1-dependent manner. Our results provide useful information for the development of novel therapeutics for management of glucocorticoids-induced avascular necrosis of the femoral head.

Gastric Volvulus with Segmental Necrosis Treated with Wedge Resection and Gastrogastrostomy.

PubMed

Merz, Alexa Elizabeth; Preston, Jennifer Francis

2017-12-01

Ischemic necrosis is a feared complication of acute gastric volvulus, occurring in 11% of patients presenting with the condition and responsible for mortality in 30%. In such cases, there are few well-validated options for surgical reconstruction. We present the case of a 77-year-old woman with intraabdominal mesenteroaxial gastric volvulus with segmental ischemic gastric necrosis who underwent wedge gastrectomy and hand-sewn gastrogastrostomy. She did well postoperatively and experienced no significant gastrointestinal complications. Gastric wedge resection with gastrogastrostomy presents a novel surgical intervention for a rare and highly morbid entity. We hope to add it to the repertoire of surgeons facing acute gastric volvulus complicated by segmental necrosis.

A case of systemic lupus erythematosus presenting as bilateral avascular necrosis of femur.

PubMed

Adikari, Madura; Gunawardane, Aloka; Illangantilaka, Sachithra; Atukorale, Himantha; Rubasinghe, Jeevanie

2016-08-05

Avascular necrosis occur as a result of diverse etiology. Chronic inflammatory conditions such as systemic lupus erythematosus considered as a recognize cause. Many cases were reported in systemic lupus erythematosus after treating with corticosteroids. We report a case of a corticosteroid naïve patient presented as bilateral avascular necrosis of femoral head and later progressed to a case of systemic lupus erythematosus. A 26 year old lady presented with right sided hip pain and diagnosed as avascular necrosis of the femoral head. After 6 months she presented a similar pain in left hip, which revealed avascular necrosis of left femoral head as well. A probable cause for her clinical presentation could not be found after extensive clinical and laboratory evaluation. Patient reported high erythrocyte sedimentation rate persistently, and over the next few years progressed as a case of systemic lupus erythematosus. Above case illustrated avascular necrosis could be an early musculoskeletal manifestation of systemic lupus erythematosus even in the absence of corticosteroid administration.

Atypical incus necrosis: a case report and literature review.

PubMed

Choudhury, N; Kumar, G; Krishnan, M; Gatland, D J

2008-10-01

We report an atypical case of ossicular necrosis affecting the incus, in the absence of any history of chronic serous otitis media. We also discuss the current theories of incus necrosis. A male patient presented with a history of right unilateral hearing loss and tinnitus. Audiometry confirmed right conductive deafness; tympanometry was normal bilaterally. He underwent a right exploratory tympanotomy, which revealed atypical erosion of the proximal long process of the incus. Middle-ear examination was otherwise normal, with a mobile stapes footplate. The redundant long process of the incus was excised and a partial ossicular replacement prosthesis was inserted, resulting in improved hearing. Ossicular pathologies most commonly affect the incus. The commonest defect is an absent lenticular and distal long process of the incus, which is most commonly associated with chronic otitis media. This is the first reported case of ossicular necrosis, particularly of the proximal long process of the incus, in the absence of chronic middle-ear pathology.

PARP1-mediated necrosis is dependent on parallel JNK and Ca2+/calpain pathways

PubMed Central

Douglas, Diana L.; Baines, Christopher P.

2014-01-01

ABSTRACT Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme that can trigger caspase-independent necrosis. Two main mechanisms for this have been proposed: one involving RIP1 and JNK kinases and mitochondrial permeability transition (MPT), the other involving calpain-mediated activation of Bax and mitochondrial release of apoptosis-inducing factor (AIF). However, whether these two mechanisms represent distinct pathways for PARP1-induced necrosis, or whether they are simply different components of the same pathway has yet to be tested. Mouse embryonic fibroblasts (MEFs) were treated with either N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) or β-Lapachone, resulting in PARP1-dependent necrosis. This was associated with increases in calpain activity, JNK activation and AIF translocation. JNK inhibition significantly reduced MNNG- and β-Lapachone-induced JNK activation, AIF translocation, and necrosis, but not calpain activation. In contrast, inhibition of calpain either by Ca2+ chelation or knockdown attenuated necrosis, but did not affect JNK activation or AIF translocation. To our surprise, genetic and/or pharmacological inhibition of RIP1, AIF, Bax and the MPT pore failed to abrogate MNNG- and β-Lapachone-induced necrosis. In conclusion, although JNK and calpain both contribute to PARP1-induced necrosis, they do so via parallel mechanisms. PMID:25052090

Ischemic necrosis of the tongue in surgical patients with septic shock: a case report.

PubMed

Cho, Jinbeom; Sung, Kiyoung; Lee, Dosang

2016-07-19

As the tongue is a well-vascularized organ, ischemic necrosis of the tongue is a rare disease entity. Critically ill patients with profound shock may experience end-organ hypoperfusion, which might result in tongue necrosis. However, to our best knowledge, there are no reports regarding ischemic necrosis of the tongue in surgical patients with septic shock. Two patients recently developed ischemic necrosis of the tongue in our surgical intensive care unit. Both patients had undergone emergent surgery for ischemic enteritis and developed postoperative septic shock. The first patient responded to critical treatment with a short period of circulatory shock, and the delivered dose of the vasopressor seemed to be acceptable. In contrast, the second patient developed postoperative refractory shock, and high-dose vasopressor treatment was required to maintain adequate tissue perfusion. Both patients developed ischemic necrosis of the tongue and died shortly after its emergence, despite vigorous resuscitation. We suggest that ischemic necrosis of the tongue is an under-reported manifestation of any type of circulatory shock, which may have a complex pathogenic mechanism. Clinicians should be aware of the possibility of ischemic necrosis of the tongue in patients with circulatory shock, even if the patient exhibits clinical improvement, as this awareness may facilitate estimation of their prognosis and preparation for clinical deterioration.

Superomedial pedicle reduction mammaplasty: increased resection weight does not increase nipple necrosis.

PubMed

Brownlee, Pamela; Chesire, David; Crandall, Marie; Murray, John

2017-11-01

The superomedial pedicle (SMP) reduction mammaplasty offers several advantages over more traditional operative techniques, such as retained sensation to the nipple areola complex (NAC) and improved preservation of long-term breast shape. However, many surgeons believe that using the SMP can cause an increase in NAC necrosis rates up to 13.1%, especially in large volume reductions. The aims of this paper are to determine the rate of nipple necrosis when performing an SMP reduction mammaplasty at our institution and establish if there is a difference in those rates based on the weight of tissue removed. We then compared our overall rate of nipple necrosis to those found using a systematic review of literature involving other pedicles to determine if this technique is equivalent to more commonly used methods. We performed a retrospective chart review of patients who underwent breast reduction surgery using SMP at a single institution between May 1, 2013, and May 1, 2015. Each breast was counted separately, and the weight of the tissue removed was recorded. Six-mo follow-up data were analyzed using the chi-square analysis to compare rates of NAC necrosis among our patients and historical cohorts. One hundred thirty-five breasts (70 patients) met inclusion criteria. Patients had a mean resection weight per breast of 1016.7 g (±478.3). There was an NAC necrosis rate of 0% in the groups where 1200 g or less of tissue were removed and 2.3% (n = 1) in the group where greater than 1200 g of tissue were removed. We found no statistically significant difference in the rate of NAC necrosis with increased resection weights, (P = 0.32). The overall rate of NAC necrosis for this study was 0.7% per breast, which is equivalent to the rates found during the systematic review of literature. In this study, the SMP breast reduction technique shows a low rate of NAC. We found no statistically significant increase in NAC necrosis rates as the volume of tissue removed increases

Histopathology of aseptic necrosis of the femoral head in sickle cell disease.

PubMed

Mukisi-Mukaza, Martin; Gomez-Brouchet, Anne; Donkerwolcke, Monique; Hinsenkamp, Maurice; Burny, Franz

2011-08-01

This study compares the histopathology of bone biopsies from patients suffering from sickle cell anaemia (homozygote SS) to heterozygote patients (SA) and homozygotes with aseptic osteonecrosis (AA). The sensitivity to bacterial infection of sickle cell patients raises the question of the aetiology of sepsis in the onset of the necrosis. To our knowledge this study is the first to analyse the histopathology of osteonecrosis of the femoral head, at its early stages, in sickle cell anaemia. At the University Hospital of Pointe-à-Pitre, from 1994 to 2007, 38 bone biopsies were obtained from adult patients with avascular necrosis of the femoral head at the time of a core decompression procedure (SS, SC: 27; AS: 5; AA: 6). The histology of the biopsies confirmed the necrosis; all bacteriological cultures were negative. Patients displaying one S gene (SS, SC, AS) compared to homozygote subjects (AA) showed a significant increase of a nonspecific inflammatory granulomatosis (p = 0.003). No relationship was observed between the radiological stages and the histology whatever the genotype (p = 0.1). Inflammatory histopathology without sepsis or advanced alteration characterises the early stages of sickle cell necrosis. This inflammatory process is absent in idiopathic avascular necrosis.

Delayed cerebral radiation necrosis following treatment for a plasmacytoma of the skull.

PubMed

Chambless, Lola B; Angel, Federica B; Abel, Ty W; Xia, Fen; Weaver, Kyle D

2010-10-25

Cerebral radiation necrosis is a relatively common complication of radiation therapy for intracranial malignancies which can also rarely be encountered after radiation of extracranial lesions of the head and neck. We present the first reported case of cerebral radiation necrosis in a patient who underwent radiation therapy for a plasmacytoma of the skull. A 68-year-old male with multiple myeloma presented with an enhancing right frontal mass, 8 years after receiving radiation therapy for a plasmacytoma of the left frontal skull. The patient underwent a diagnostic and therapeutic craniotomy for a presumed neoplastic lesion. The pathologic diagnosis made in this case was delayed radiation necrosis. The patient was followed for over a year during which this process continued to evolve before the ultimate resolution of his clinical symptoms and radiographic abnormality. This case highlights the importance of considering radiation necrosis in the differential diagnosis of any patient with an intracranial mass and a history of radiation for an extracranial head and neck malignancy, regardless of timing and laterality. This case also provides unique insights into the ongoing debate regarding the role of the aberrant immune response in the pathogenesis of delayed cerebral radiation necrosis.

[RESEARCH PROGRESS OF EXPERIMENTAL ANIMAL MODELS OF AVASCULAR NECROSIS OF FEMORAL HEAD].

PubMed

Yu, Kaifu; Tan, Hongbo; Xu, Yongqing

2015-12-01

To summarize the current researches and progress on experimental animal models of avascular necrosis of the femoral head. Domestic and internation literature concerning experimental animal models of avascular necrosis of the femoral head was reviewed and analyzed. The methods to prepare the experimental animal models of avascular necrosis of the femoral head can be mainly concluded as traumatic methods (including surgical, physical, and chemical insult), and non-traumatic methods (including steroid, lipopolysaccharide, steroid combined with lipopolysaccharide, steroid combined with horse serum, etc). Each method has both merits and demerits, yet no ideal methods have been developed. There are many methods to prepare the experimental animal models of avascular necrosis of the femoral head, but proper model should be selected based on the aim of research. The establishment of ideal experimental animal models needs further research in future.

Prognostic significance of extensive necrosis in renal cell carcinoma.

PubMed

Collins, Jennifer; Epstein, Jonathan I

2017-08-01

Few studies using the current classification of renal cell carcinoma (RCC) have looked at a large number of cases with near total necrosis. We identified 21 cases of resections of RCC with >90% necrosis from the archives of Johns Hopkins Hospital between 2000 and 2015. Patients' mean age was 59 years (43-77) with 16 men (76%); 12 cases (57%) were papillary RCC, 4 clear cell papillary RCC (19%), 4 clear cell RCC (19%), and 1 unclassified with sarcomatoid differentiation (5%). International Society of Urological Pathology (ISUP) nucleolar grade was grade 1 (9 cases) or grade 2 (9 cases). Two cases were ISUP nucleolar grade 3, and 1 case was grade 4. Pathological stage was low (pT1-2) in 20 (95%) with the unclassified RCC with sarcomatoid differentiation RCC stage pT3a. Mean tumor size was 6.3 cm (1.2-17). In 52% (11) of cases, it was difficult to identify viable tumor, requiring multiple sections; 4 cases of papillary RCC were diagnosed in part due to necrotic tumor "ghost" architecture. Follow-up was available in 17 cases (81%) with a mean follow-up of 59 months. Thirteen patients (62%) are alive without disease. The patient with unclassified carcinoma with sarcomatoid differentiation died of cancer, and 2 died due to causes unrelated to cancer. One patient (5%) with low-grade clear cell RCC developed metastases but had a contralateral RCC. In the setting of a low-grade RCC, extensive necrosis does not have an adverse prognosis. In summary, our data, together with a prior study from our institution, comprise one of the largest cohorts of extensively (>90%) necrotic RCCs and suggests that in the setting of a low-grade RCC, it portends a good prognosis (only 2/36 cases showing progression (6%) on follow-up). However, we did identify a single case of high-grade RCC with an adverse prognosis and therefore, careful attention to tumor grade and classification is critical. The presence of tumor necrosis as a prognosticator in RCCs is complex, and despite its well

Is the necrosis/wall ADC ratio useful for the differentiation of benign and malignant breast lesions?

PubMed

Durur-Subasi, Irmak; Durur-Karakaya, Afak; Karaman, Adem; Seker, Mehmet; Demirci, Elif; Alper, Fatih

2017-05-01

To determine whether the necrosis/wall apparent diffusion coefficient (ADC) ratio is useful for the malignant-benign differentiation of necrotic breast lesions. Breast MRI was performed using a 3-T system. In this retrospective study, calculation of the necrosis/wall ADC ratio was based on ADC values measured from the necrosis and from the wall of malignant and benign breast lesions by diffusion-weighted imaging (DWI). By synchronizing post-contrast T 1 weighted images, the separate parts of wall and necrosis were maintained. All the diagnoses were pathologically confirmed. Statistical analyses were conducted using an independent sample t-test and receiver operating characteristic analysis. The intraclass and interclass correlations were evaluated. A total of 66 female patients were enrolled, 38 of whom had necrotic breast carcinomas and 28 of whom had breast abscesses. The ADC values were obtained from both the wall and necrosis. The mean necrosis/wall ADC ratio (± standard deviation) was 1.61 ± 0.51 in carcinomas, and it was 0.65 ± 0.33 in abscesses. The area under the curve values for necrosis ADC, wall ADC and the necrosis/wall ADC ratio were 0.680, 0.068 and 0.942, respectively. A wall/necrosis ADC ratio cut-off value of 1.18 demonstrated a sensitivity of 97%, specificity of 93%, a positive-predictive value of 95%, a negative-predictive value of 96% and an accuracy of 95% in determining the malignant nature of necrotic breast lesions. There was a good intra- and interclass reliability for the ADC values of both necrosis and wall. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating breast carcinomas from abscesses using DWI. Advances in knowledge: ADC values of the necrosis obtained by DWI are valuable for malignant-benign differentiation in necrotic breast lesions. The necrosis/wall ADC ratio appears to be a reliable and promising tool in the breast imaging field.

Is the necrosis/wall ADC ratio useful for the differentiation of benign and malignant breast lesions?

PubMed Central

Durur-Karakaya, Afak; Karaman, Adem; Seker, Mehmet; Demirci, Elif; Alper, Fatih

2017-01-01

Objective: To determine whether the necrosis/wall apparent diffusion coefficient (ADC) ratio is useful for the malignant–benign differentiation of necrotic breast lesions. Methods: Breast MRI was performed using a 3-T system. In this retrospective study, calculation of the necrosis/wall ADC ratio was based on ADC values measured from the necrosis and from the wall of malignant and benign breast lesions by diffusion-weighted imaging (DWI). By synchronizing post-contrast T1 weighted images, the separate parts of wall and necrosis were maintained. All the diagnoses were pathologically confirmed. Statistical analyses were conducted using an independent sample t-test and receiver operating characteristic analysis. The intraclass and interclass correlations were evaluated. Results: A total of 66 female patients were enrolled, 38 of whom had necrotic breast carcinomas and 28 of whom had breast abscesses. The ADC values were obtained from both the wall and necrosis. The mean necrosis/wall ADC ratio (± standard deviation) was 1.61 ± 0.51 in carcinomas, and it was 0.65 ± 0.33 in abscesses. The area under the curve values for necrosis ADC, wall ADC and the necrosis/wall ADC ratio were 0.680, 0.068 and 0.942, respectively. A wall/necrosis ADC ratio cut-off value of 1.18 demonstrated a sensitivity of 97%, specificity of 93%, a positive-predictive value of 95%, a negative-predictive value of 96% and an accuracy of 95% in determining the malignant nature of necrotic breast lesions. There was a good intra- and interclass reliability for the ADC values of both necrosis and wall. Conclusion: The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating breast carcinomas from abscesses using DWI. Advances in knowledge: ADC values of the necrosis obtained by DWI are valuable for malignant-benign differentiation in necrotic breast lesions. The necrosis/wall ADC ratio appears to be a reliable and promising tool in the breast imaging field. PMID

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.

Avascular Necrosis of the Femoral Head.

PubMed

Seijas, Roberto; Sallent, Andrea; Rivera, Eila; Ares, Oscar

2017-12-29

About 250000 patients are operated on annually for hip arthroplasty in the USA alone. Of this number, about 10% the cause of their osteoarthritis is the avascular necrosis of the femoral head. But the causes of necrosis are multiple and many of them are still unknown. That is why small advances in etiopathogenesis, diagnosis and treatment of different causes are very important in order to reduce the number of affected patients. It may seem that small changes, studies focused on the details of different diseases do not bring great changes to science, but it is these small changes that end up adding great evolutions in our knowledge. In addition, the changes of recent years, are not focused on our specialty in technical or anatomical evolutions exclusively, but are often based on biological bases, which is the branch that evolves more within trauma and orthopedics. That is why open and constant minds are what help us move forward.

The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games.

PubMed

Hehlgans, Thomas; Pfeffer, Klaus

2005-05-01

The members of the tumour necrosis factor (TNF)/tumour necrosis factor receptor (TNFR) superfamily are critically involved in the maintenance of homeostasis of the immune system. The biological functions of this system encompass beneficial and protective effects in inflammation and host defence as well as a crucial role in organogenesis. At the same time, members of this superfamily are responsible for host damaging effects in sepsis, cachexia, and autoimmune diseases. This review summarizes recent progress in the immunobiology of the TNF/TNFR superfamily focusing on results obtained from animal studies using gene targeted mice. The different modes of signalling pathways affecting cell proliferation, survival, differentiation, apoptosis, and immune organ development as well as host defence are reviewed. Molecular and cellular mechanisms that demonstrate a therapeutic potential by targeting individual receptors or ligands for the treatment of chronic inflammatory or autoimmune diseases are discussed.

Regulated necrosis and its implications in toxicology.

PubMed

Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi

2015-07-03

Recent research developments have revealed that caspase-dependent apoptosis is not the sole form of regulated cell death. Caspase-independent, but genetically regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and the recently discovered ferroptosis and autosis. Importantly, regulated necrosis can be modulated by small molecule inhibitors/activators, confirming the cell autonomous mechanism of these forms of cell death. The success of small molecule-mediated manipulation of regulated necrosis has produced great changes in the field of cell death research, and has also brought about significant changes in the fields of pharmacology as well as toxicology. In this review, we intend to summarize the modes of regulated cell death other than apoptosis, and discuss their implications in toxicology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Giant Cell Arteritis Presenting as Scalp Necrosis

PubMed Central

Maidana, Daniel E.; Muñoz, Silvia; Acebes, Xènia; Llatjós, Roger; Jucglà, Anna; Álvarez, Alba

2011-01-01

The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness. PMID:21789466

Concurrent Acute Retinal Necrosis in a Patient With Iridocorneal Endothelial Syndrome.

PubMed

Vignesh, A P; Srinivasan, Renuka

2016-11-01

To report a rare case of concurrent acute retinal necrosis in a patient with iridocorneal endothelial syndrome (ICE). Case report. A 42-year-old woman showed acute diminution of vision in the right eye. Her fundus examination revealed features of acute retinal necrosis. She had also experienced gradual diminution of vision in her left eye for 5 years. The examination of her left eye revealed corneal edema with mild corectopia and increased intraocular pressure with abnormal endothelium on specular microscopy pointing to a diagnosis of ICE. This is a rare case where concurrent acute retinal necrosis and ICE syndrome are present in the same patient, possibly pointing to a common viral etiology causing both entities.

TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells

PubMed Central

2014-01-01

Background The cytokine TRAIL represents one of the most promising candidates for the apoptotic elimination of tumor cells, either alone or in combination therapies. However, its efficacy is often limited by intrinsic or acquired resistance of tumor cells to apoptosis. Programmed necrosis is an alternative, molecularly distinct mode of programmed cell death that is elicited by TRAIL under conditions when the classical apoptosis machinery fails or is actively inhibited. The potential of TRAIL-induced programmed necrosis in tumor therapy is, however, almost completely uncharacterized. We therefore investigated its impact on a panel of tumor cell lines of wide-ranging origin. Methods Cell death/viability was measured by flow cytometry/determination of intracellular ATP levels/crystal violet staining. Cell surface expression of TRAIL receptors was detected by flow cytometry, expression of proteins by Western blot. Ceramide levels were quantified by high-performance thin layer chromatography and densitometric analysis, clonogenic survival of cells was determined by crystal violet staining or by soft agarose cloning. Results TRAIL-induced programmed necrosis killed eight out of 14 tumor cell lines. Clonogenic survival was reduced in all sensitive and even one resistant cell lines tested. TRAIL synergized with chemotherapeutics in killing tumor cell lines by programmed necrosis, enhancing their effect in eight out of 10 tested tumor cell lines and in 41 out of 80 chemotherapeutic/TRAIL combinations. Susceptibility/resistance of the investigated tumor cell lines to programmed necrosis seems to primarily depend on expression of the pro-necrotic kinase RIPK3 rather than the related kinase RIPK1 or cell surface expression of TRAIL receptors. Furthermore, interference with production of the lipid ceramide protected all tested tumor cell lines. Conclusions Our study provides evidence that TRAIL-induced programmed necrosis represents a feasible approach for the elimination of

FOCAL OR INSULAR NECROSIS PRODUCED BY THE BACILLUS OF TUBERCULOSIS.

PubMed

Le Count, E R

1897-11-01

1. It must be accepted from a comparison between the histological changes described in the focal necroses due to abrin and ricin, diphtheria, eclampsia, blood-serum intoxication, typhoid fever, lobar pneumonia and glanders, and those described here in three cases of tuberculosis, that the last are also instances of focal necrosis. 2. It may be claimed that the areas of necrosis in the three cases of tuberculosis had their origin in ischaemia, for the reason that they were numerous in the spleen and were not found in the kidney. Against such an explanation of their causation are the facts: that other forms of necrosis affect frequently the spleen and seldom the kidney; that thrombosis of vessels or any fixed relation of the areas in the spleen to blood-vessels could not be established; that the tubercle bacilli were invariably present; and lastly and of no slight importance, that these necroses were all present in cases of marked marasmus. 3. That the areas of necrosis in these three cases might be phenomena resulting from a mixed infection with pyogenic bacteria is possible, but no groups, colonies or even single bodies could be found which answered to the requirements in shape or staining properties for such bacteria. Even were it the case that the focal necroses here presented are the histological lesions of a septicaemia occurring as a complication of tuberculosis, the presence of the bacillus of tuberculosis in the areas of necrosis would still require explanation. 4. Lastly, it is not unreasonable to suppose that a diminished resistance on the part of the tissues incidental to marasmus is an important factor in the production of these necrotic lesions.

Post Traumatic Avascular Necrosis of the Proximal Carpal Row--A Case Report.

PubMed

Manohara, Ruben; Sebastin, Sandeep Jacob; Puhaindran, Mark Edward

2015-10-01

We report a case of avascular necrosis of the scaphoid, lunate and triquetrum in a young 21-year-old patient, after a purely ligamentous peri-lunate dislocation of the wrist. He presented with a Mayfield III peri-lunate dislocation after a road traffic accident and underwent an open reduction and internal fixation. Post-operatively, the scapho-lunate gap widened after removal of the temporary K-wires, and he gradually developed avascular necrosis of the scaphoid, lunate and triquetrum, and osteoarthritis of his wrist. We present this unusual case of simultaneous avascular necrosis of multiple carpal bones and discuss the possible risk factors and subsequent management plans for this complex injury. Our patient has no identifiable contributing factors to developing avascular necrosis. We suspect that the violence of the injury and surgery may have compromised the circulation, and advise caution when treating and counseling these patients pre-operatively.

Pediatric Digital Necrosis Secondary to Dressing Application: A Case Series.

PubMed

Bjorklund, Kim A; Rice, Dahlia M; Amalfi, Ashley N

2018-04-01

Pediatric digital necrosis resulting in revision amputation is a devastating outcome following digital dressing application. We report a series of 4 pediatric patients (age: 21 months-11 years) who presented for surgical consultation related to digital ischemia and irreversible necrosis following the application of Coban digital dressings. A review of the literature demonstrated that such injuries had not previously been described. In our case series, Coban dressing was utilized as a deterrent for thumb sucking, fingertip tuft fractures with nail bed lacerations, and a phalanx fracture secondary to crush injury. All 4 children suffered digital necrosis secondary to Coban dressings and ultimately required revision amputation. We discuss risks factors, application practices, and strategies to minimize complications with digital dressings in the pediatric population with the intent of creating awareness among hand surgeons to help promote safe practices and improve patient outcomes.

EVALUATION OF CONTRAST-ENHANCED ULTRASONOGRAPHY AS A METHOD FOR DETECTING GALLBLADDER NECROSIS OR RUPTURE IN DOGS.

PubMed

Bargellini, Paolo; Orlandi, Riccardo; Paloni, Chiara; Rubini, Giuseppe; Fonti, Paolo; Peterson, Mark E; Rishniw, Mark; Boiti, Cristiano

2016-11-01

Gall bladder necrosis and rupture are life-threatening conditions in dogs requiring surgical intervention and early diagnosis is essential. Human patients with suspected gall bladder necrosis/rupture are commonly evaluated with contrast-enhanced ultrasonography (CEUS), however this procedure has not been described in dogs with suspected gall bladder necrosis/rupture. In a prospective diagnostic cohort study, CEUS (using SonoVue contrast medium) was performed in 93 dogs with gallbladder lesions identified by abdominal conventional ultrasonography. Necrosis/rupture was identified by CEUS as a focal lack of enhancement of the gallbladder wall. Dogs with positive CEUS finding for necrosis/rupture (complete lack of regional wall enhancement) underwent immediate surgery as did dogs with other biliary disorders requiring surgery. Dogs with negative CEUS findings or those not requiring surgery were managed medically. In cases undergoing surgery, necrosis/rupture was confirmed intraoperatively (and via histopathology). Absence of necrosis/rupture was confirmed either intraoperatively (via histopathology) or was assumed to be absent by complete recovery with medical management. Forty-nine dogs underwent surgery and cholecystectomy: 24 had necrosis/rupture. CEUS was more accurate (100% sensitive and specific) in diagnosing gallbladder wall necrosis/rupture than conventional ultrasonography (75% sensitive and 81% specific) (P < 0.03). In conclusion, CEUS provides accurate characterization of gallbladder wall integrity that can impact decisions regarding clinical management, either surgical or medical. © 2016 American College of Veterinary Radiology.

[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.

Coupling of Rigor Mortis and Intestinal Necrosis during C. elegans Organismal Death.

PubMed

Galimov, Evgeniy R; Pryor, Rosina E; Poole, Sarah E; Benedetto, Alexandre; Pincus, Zachary; Gems, David

2018-03-06

Organismal death is a process of systemic collapse whose mechanisms are less well understood than those of cell death. We previously reported that death in C. elegans is accompanied by a calcium-propagated wave of intestinal necrosis, marked by a wave of blue autofluorescence (death fluorescence). Here, we describe another feature of organismal death, a wave of body wall muscle contraction, or death contraction (DC). This phenomenon is accompanied by a wave of intramuscular Ca 2+ release and, subsequently, of intestinal necrosis. Correlation of directions of the DC and intestinal necrosis waves implies coupling of these death processes. Long-lived insulin/IGF-1-signaling mutants show reduced DC and delayed intestinal necrosis, suggesting possible resistance to organismal death. DC resembles mammalian rigor mortis, a postmortem necrosis-related process in which Ca 2+ influx promotes muscle hyper-contraction. In contrast to mammals, DC is an early rather than a late event in C. elegans organismal death. VIDEO ABSTRACT. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

High serum creatinine in acute pancreatitis: a marker for pancreatic necrosis?

PubMed

Lankisch, Paul Georg; Weber-Dany, Bettina; Maisonneuve, Patrick; Lowenfels, Albert B

2010-05-01

High serum creatinine is a well-known unfavorable prognostic parameter in acute pancreatitis. Elevated creatinine at 48 h after admission was recently described as a marker for pancreatic necrosis. As pancreatic necrosis is a serious complication of acute pancreatitis and its identification by a simple single laboratory test would be very helpful, the aim of this study was to test that statement. In a prospective multicenter study of 462 patients with a first attack of acute pancreatitis, serum creatinine was determined on admission, and at 24 and 48 h thereafter, and compared with the findings of contrast-enhanced computed tomography (CT) performed within 96 h of admission. Pancreatic necrosis was present in 62 (13%) of the patients. Serum creatinine levels (abnormal > or = 2 mg/dl) on admission and after 24 and 48 h were evaluated vs. the presence or absence of pancreatic necrosis. Sensitivity rates varied between 14 and 23%, specificity between 95 and 97%, positive predictive values between 41 and 50%, and negative predictive values between 87 and 89%. Receiver operating characteristic curves revealed an area under the curve of between 0.604 and 0.669. An elevated serum creatinine concentration at any time during the first 48 h of admission is not a marker for pancreatic necrosis in a first attack of acute pancreatitis. If serum creatinine is normal, necrotizing pancreatitis is unlikely, and contrast-enhanced CT need not be performed unless complications occur and/or the patient's condition deteriorates.

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

Immunodiagnosis of groundnut and watermelon bud necrosis viruses using polyclonal antiserum to recombinant nucleocapsid protein of Groundnut bud necrosis virus.

PubMed

Jain, R K; Pandey, Amar N; Krishnareddy, M; Mandal, Bikash

2005-12-01

In vitro gene expression strategy was used for the production of polyclonal antiserum to the nucleocapsid protein (NP) of Groundnut bud necrosis virus (GBNV). The GBNV NP gene from cowpea isolate was cloned into 6x His-tagged UA cloning vector and expressed in Escherichia coli [M15] cells. The fusion protein was detected in insoluble fraction and was purified by using Ni-NTA agarose resin. The purified 6x His-fusion protein ( approximately 32 kDa) was used for immunisation to produce a high titre polyclonal antiserum. The antiserum to the NP of GBNV at 1:4000 dilution detected successfully natural infection of GBNV and Watermelon bud necrosis virus in a wide range of cucurbitaceous, leguminous and solanaceous hosts from different locations.

Computed tomography findings of gaseous necrosis in epithelial ovarian cancer: a report of three cases.

PubMed

Cronin, Paul; Crosse, Barbara; Lane, Geoff; Spencer, John A

2002-01-01

Necrosis in pathologic specimens of ovarian cancer is well documented; however, computed tomography (CT) evidence of gaseous necrosis in the absence of fistulation with bowel has not yet been described. We report three cases of ovarian adenocarcinoma that on CT showed evidence of gross gaseous necrosis, mimicking a pelvic abscess.

Factors influencing notching and necrosis of Dracaena deremensis Warneckii foliage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conover, C.A.; Poole, R.T.

1973-01-01

Quality of Dracaena deremensis Warneckii Engler. cuttings imported from Puerto Rico deteriorated during propagation and growing in commercial nurseries in Apopka, Florida. Foliage became necrotic with reddish brown spots occurring along edges, particularly in the white areas. As plants increased in size, notches occurred in the leaves. Tissue analyses indicated that Ca and Cu content decreased, F increased and Mg, Fe, Zn and Mn increased then decreased with time from importation. To determine possible method of alleviating the notching and necrosis, three 3x2x2 factorial experiments were established in 3 shade levels. Varying rates of boron, Osmocote (18-6-12) and Perk, amore » micronutrient blend, were applied to rooted Warneckii. Osmocote and Perk levels had no effect on necrosis or notching. Increasing light increased necrosis and increasing B decreased no. of notched leaves of plants grown under 80% shade. 11 references, 4 tables.« less

In vitro and in vivo expression of interleukin-1alpha and tumor necrosis factor-alpha mRNA in pemphigus vulgaris: interleukin-1alpha and tumor necrosis factor-alpha are involved in acantholysis.

PubMed

Feliciani, C; Toto, P; Amerio, P; Pour, S M; Coscione, G; Shivji, G; Wang, B; Sauder, D N

2000-01-01

Keratinocyte-derived cytokines have been implicated in the pathogenesis of a number of skin diseases. In this study we examined the possible role of keratinocyte-derived cytokines in the development of acantholysis in pemphigus vulgaris. Nineteen patients with pemphigus vulgaris, demonstrating the characteristic clinical, pathologic, and immunopathologic findings were studied. In situ immunolabeling demonstrated the presence of two cytokines interleukin-1alpha and tumor necrosis factor-alpha, in lesional and perilesional areas. Results were confirmed by reverse transcriptase-polymerase chain reaction, demonstrating overexpression of both cytokines in vivo. To study the role of these cytokines in the pathogenesis of pemphigus vulgaris both in vitro and in vivo studies were performed. The results of the in vitro study demonstrated that pemphigus vulgaris IgG induced interleukin-1alpha and tumor necrosis factor-alpha mRNA in the skin. The potential pathogenic role of these mediators was demonstrated by a blocking study using antibodies against human interleukin-1alpha and tumor necrosis factor-alpha in keratinocytes cultures. A combination of anti-interleukin-1alpha and anti-tumor necrosis factor-alpha antibodies inhibited in vitro pemphigus vulgaris IgG induced acantholysis. To confirm the role of interleukin-1 and tumor necrosis factor-alpha in pemphigus, we utilized passive transfer studies using interleukin-1 deficient mice (ICE-/-, interleukin-1beta-/-) and tumor necrosis factor-alpha receptor deficient mice (TNFR1R2-/-). Both groups demonstrated a decreased susceptibility to the passive transfer of pemphigus. Our data support the role of cytokines interleukin-1 and tumor necrosis factor-alpha in the pathogenesis of pemphigus vulgaris.

SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis.

PubMed

Choi, Seon-Guk; Kim, Hyunjoo; Jeong, Eun Il; Lee, Ho-June; Park, Sungwoo; Lee, Song-Yi; Lee, Hyeon-Jeong; Lee, Seong Won; Chung, Chin Ha; Jung, Yong-Keun

2017-01-15

Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury. Copyright © 2017 American Society for Microbiology.

SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis

PubMed Central

Choi, Seon-Guk; Kim, Hyunjoo; Jeong, Eun Il; Lee, Ho-June; Park, Sungwoo; Lee, Song-Yi; Lee, Hyeon-Jeong; Lee, Seong Won; Chung, Chin Ha

2016-01-01

ABSTRACT Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury. PMID:27799292

Tumour necrosis factor-α/interleukin-10 ratio in patients with obstructive sleep apnoea hypopnoea syndrome.

PubMed

Jiang, H; Cao, H; Wang, P; Liu, W; Cao, F; Chen, J

2015-01-01

To explore the significance of the tumour necrosis factor-α/interleukin-10 ratio and the effect of continuous positive airway pressure in patients with different degrees of obstructive sleep apnoea hypopnoea syndrome severity. This study comprised 135 patients with obstructive sleep apnoea hypopnoea syndrome and 94 control subjects. Tumour necrosis factor-α and tumour necrosis factor-α/interleukin-10 ratio values were significantly higher in the obstructive sleep apnoea hypopnoea syndrome group than in the control group, but interleukin-10 was significantly lower. Tumour necrosis factor-α/interleukin-10 ratio values increased in line with the severity of obstructive sleep apnoea hypopnoea syndrome. In multivariate analysis, the tumour necrosis factor-α/interleukin-10 ratio correlated positively with the apnoea-hypopnoea index and all indices of obstructive sleep apnoea hypopnoea syndrome, except for age, body mass index and neck circumference. After one month of continuous positive airway pressure therapy, levels of tumour necrosis factor-α decreased; interleukin-10 showed no change. The results suggest that inflammation is activated and anti-inflammatory cytokines are decreased in obstructive sleep apnoea hypopnoea syndrome patients. Tumour necrosis factor-α/interleukin-10 ratio may prove useful for severity monitoring and management of obstructive sleep apnoea hypopnoea syndrome patients, and may reduce the need for polysomnography.

Navigation to the graveyard-induction of various pathways of necrosis and their classification by flow cytometry.

PubMed

Janko, Christina; Munoz, Luis; Chaurio, Ricardo; Maueröder, Christian; Berens, Christian; Lauber, Kirsten; Herrmann, Martin

2013-01-01

Apoptosis and necrosis reflect the program of cell death employed by a dying cell and the final stage of death, respectively. Whereas apoptosis is defined as a physiological, highly organized cell death process, necrosis is commonly considered to be accidental and uncontrolled. Physiological and weak pathological death stimuli preferentially induce apoptosis, while harsh non-physiological insults often immediately instigate (primary) necrosis. If an apoptosing cell transits into a phase of plasma membrane disintegration, this stage of death is referred to as secondary or post-apoptotic necrosis.Here, we present several conditions that stimulate primary and/or secondary necrosis and show that necrosis displays considerably different time courses. For subclassification of necrotic phenotypes we employed a flow cytometric single-tube 4-color staining technique including annexin A5-FITC, propidium iodide, DiIC1(5), and Hoechst 33342.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Xiaoyu; Perez-Torres, Carlos J.; Thotala, Dinesh

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: Micemore » 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.« less

RIP3: a molecular switch for necrosis and inflammation

PubMed Central

Moriwaki, Kenta; Chan, Francis Ka-Ming

2013-01-01

The receptor-interacting protein kinase 3 (RIP3/RIPK3) has emerged as a critical regulator of programmed necrosis/necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation. RIP3 activation is tightly regulated by phosphorylation, ubiquitination, and caspase-mediated cleavage. These post-translational modifications coordinately regulate the assembly of a macromolecular signaling complex termed the necrosome. Recently, several reports indicate that RIP3 can promote inflammation independent of its pronecrotic activity. Here, we review our current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases. PMID:23913919

[S3 Guideline. Part 3: Non-Traumatic Avascular Necrosis in Adults - Surgical Treatment of Atraumatic Avascular Femoral Head Necrosis in Adults].

PubMed

Maus, U; Roth, A; Tingart, M; Rader, C; Jäger, M; Nöth, U; Reppenhagen, S; Heiss, C; Beckmann, J

2015-10-01

The present article describes the guidelines for the surgical treatment of atraumatic avascular necrosis (aFKN). These include joint preserving and joint replacement procedures. As part of the targeted literature, 43 publications were included and evaluated to assess the surgical treatment. According to the GRADE and SIGN criteria level of evidence (LoE), grade of recommendation (EC) and expert consensus (EK) were listed for each statement and question. The analysed studies have shown that up to ARCO stage III, joint-preserving surgery can be performed. A particular joint-preserving surgery currently cannot be recommended as preferred method. The selection of the method depends on the extent of necrosis. Core decompression performed in stage ARCO I (reversible early stage) or stage ARCO II (irreversible early stage) with medial or central necrosis with an area of less than 30 % of the femoral head shows better results than conservative therapy. In ARCO stage III with infraction of the femoral head, the core decompression can be used for a short-term pain relief. For ARCO stage IIIC or stage IV core decompression should not be performed. In these cases, the indication for implantation of a total hip replacement should be checked. Additional therapeutic procedures (e.g., osteotomies) and innovative treatment options (advanced core decompression, autologous bone marrow, bone grafting, etc.) can be discussed in the individual case. In elective hip replacement complications and revision rates have been clearly declining for decades. In the case of an underlying aFKN, however, previous joint-preserving surgery (osteotomies and grafts in particular) can complicate the implantation of a THA significantly. However, the implant life seems to be dependent on the aetiology. Higher revision rates for avascular necrosis are particularly expected in sickle cell disease, Gaucher disease, or kidney transplantation patients. Furthermore, the relatively young age of the patient

Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis.

PubMed

Borab, Zachary; Mirmanesh, Michael D; Gantz, Madeleine; Cusano, Alessandro; Pu, Lee L Q

2017-04-01

Every year, 1.2 million cancer patients receive radiation therapy in the United States. Late radiation tissue injury occurs in an estimated 5-15% of these patients. Tissue injury can include skin necrosis, which can lead to chronic nonhealing wounds. Despite many treatments available to help heal skin necrosis such as hyperbaric oxygen therapy, no clinical guidelines exist and evidence is lacking. The purpose of this review is to identify and comprehensively summarize studies published to date to evaluate the effectiveness of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Adhering to PRISMA guidelines, a systematic review of currently published articles was performed, evaluating the use of hyperbaric oxygen to treat skin necrosis. Eight articles were identified, including one observational cohort, five case series, and two case reports. The articles describe changes in symptoms and alteration in wound healing of radiation-induced skin necrosis after treatment with hyperbaric oxygen therapy. Hyperbaric oxygen therapy is a safe intervention with promising outcomes; however, additional evidence is needed to endorse its application as a relevant therapy in the treatment of radiation-induced skin necrosis. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Human-specific bacterial pore-forming toxins induce programmed necrosis in erythrocytes.

PubMed

LaRocca, Timothy J; Stivison, Elizabeth A; Hod, Eldad A; Spitalnik, Steven L; Cowan, Peter J; Randis, Tara M; Ratner, Adam J

2014-08-26

A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis. In this work, we provide the first description of a new form of programmed cell death in erythrocytes (RBCs) that occurs as a consequence of cellular attack by human-specific bacterial toxins. By defining a new RBC

Spinal bone marrow necrosis with vertebral compression fracture: differentiation of BMN from AVN.

PubMed

Nix, J S; Fitzgerald, R T; Samant, R S; Harrison, M; Angtuaco, E J

2014-09-01

Bone marrow necrosis (BMN) is a rare malignancy-associated hematologic disorder characterized by necrosis of myeloid and stromal marrow elements with preservation of cortical bone. Overlap between the imaging appearances of BMN and avascular necrosis (AVN) raises the potential for diagnostic confusion. We report a case of BMN presenting with a traumatic multi-level vertebral body collapse, and finding that may potentially confound distinction between the two entities. We discuss important pathophysiologic, clinical, and radiologic differences between BMN and AVN with emphasis on features important in the differential diagnosis.

Aseptic Bone Necrosis Among U.S. Navy Divers: Survey of 934 Nonrandomly Selected Personnel

DTIC Science & Technology

1977-06-01

Health, Education, and Welfare, Washington, D.C. Kawashima, M., T. Torisu, K. Hayashi, and Y. Kamo. 1974. Avascular bone necrosis in Japanese diving...5ÜL ^4- P=- 7 RESEM^a^ATORY SUBMARINE BASE, GROTON, CONN. REPORT NUMBER 854 ASEPTIC BONE NECROSIS AMONG U. S. NAVY DIVERS: Survey of 934...Approved for public release; distribution unlimited SUMMARY PAGE THE PROBLEM Aseptic boire~ necrosis tABN) has beelTknown toT5e~ associated with

Evaluation of radiation necrosis and malignant glioma in rat models using diffusion tensor MR imaging

PubMed Central

Wang, Silun; Chen, Yifei; Lal, Bachchu; Ford, Eric; Tryggestad, Erik; Armour, Michael; Yan, Kun; Laterra, John; Zhou, Jinyuan

2011-01-01

Standard MRI cannot distinguish between radiation necrosis and tumor progression; however, this distinction is critical in the assessment of tumor response to therapy. In this study, one delayed radiation necrosis model (dose, 40 Gy; radiation field, 10 × 10 mm2; n = 13) and two orthotopic glioma models in rats (9L gliosarcoma, n = 8; human glioma xenografts, n = 5) were compared using multiple DTI indices. A visible isotropic apparent diffusion coefficient (ADC) pattern was observed in the lesion due to radiation necrosis, which consisted of a hypointense central zone and a hyperintense peripheral zone. There were significantly lower ADC, parallel diffusivity, and perpendicular diffusivity in the necrotic central zone than in the peripheral zone (all p < 0.001). When radiation-induced necrosis was compared with viable tumor, radiation necrosis had significantly lower ADC than 9L gliosarcoma and human glioma xenografts (both p < 0.01) in the central zone, and significantly lower FA than 9L gliosarcoma (p = 0.005) and human glioma xenografts (p = 0.012) in the peripheral zone. Histological analysis revealed parenchymal coagulative necrosis in the central zone, and damaged vessels and reactive astrogliosis in the peripheral zone. These data suggest that qualitative and quantitative analysis of the DTI maps can provide useful information by which to distinguish between radiation necrosis and viable glioma. PMID:21948114

Trigger wrist caused by avascular necrosis of the capitate: a case report.

PubMed

Matsui, Yuichiro; Kawamura, Daisuke; Kida, Hiroaki; Hatanaka, Kanako C; Iwasaki, Norimasa

2018-03-27

Trigger wrist is a rare condition first described by Marti in 1960, and various causes have been reported. The condition mostly occurs with finger flexion and extension, and rarely with flexion and extension of the wrist itself. Avascular necrosis of the capitate is also a rare condition, first described by Jönsson in 1942. While some reports of this condition have been published, little is known about its etiology. Therefore, no established treatment exists. We report a case of trigger wrist caused by avascular necrosis of the capitate. A 16-year-old right-handed male who was a high school handball player was referred to our department from a nearby hospital 5 months after the onset of pain in the dorsal aspect of the right wrist, with an unknown cause. At the previous hospital, imaging findings led to a diagnosis of avascular necrosis of the capitate, and conservative treatment with a wrist brace did not improve the pain. At the initial visit to our department, the patient was noted to have a painful trigger wrist that was brought on by wrist flexion and extension. Preoperative imaging findings led to a diagnosis of trigger wrist caused by capitolunate instability secondary to avascular necrosis of the capitate. We performed a partial excision of the proximal capitate with tendon ball interposition. Two years after surgery, the patient's clinical outcome was favorable, with no recurrence of wrist pain or triggering. Both trigger wrist and avascular necrosis of the capitate are rare disorders. When a patient presents with painful triggering at the wrist, surgeons must bear in mind that avascular necrosis of the capitate may result in this phenomenon. We recommend partial excision of the proximal capitate with tendon ball interposition for the treatment of this lesion.

Acute retinal necrosis as a novel complication of chickenpox in adults.

PubMed Central

Matsuo, T; Koyama, M; Matsuo, N

1990-01-01

Three patients in their 20s suffered from chickenpox while in an immunocompromised state: one in pregnancy, one during a long course of corticosteroid for severe nephrotic syndrome, and the third with repeated upper airway infection due to bronchiectasis. They developed acute retinal necrosis about three weeks after the onset of chickenpox. Since acute retinal necrosis threatens sight, this unusual complication of chickenpox in adults needs serious consideration. Images PMID:2378860

Postoperative pneumatosis intestinalis (PI) and portal venous gas (PVG) may indicate bowel necrosis: a 52-case study.

PubMed

Higashizono, Kazuya; Yano, Hideaki; Miyake, Ouki; Yamasawa, Kunihiro; Hashimoto, Masanori

2016-07-08

The significance of pneumatosis intestinalis (PI) and portal venous gas (PVG) is controversial. This retrospective study evaluated the risk factors for bowel necrosis in patients with PI and/or PVG. Between 2002 and 2015, 52 patients were diagnosed with PI and/or PVG and were included in this study. The patients were classified according to the presence or absence of bowel necrosis in surgical findings or at autopsy. Patient characteristics and clinical findings related to bowel necrosis were investigated. Bowel necrosis was diagnosed in 17 (32.7 %) patients. Amongst these 17, 10 patients received salvage surgical intervention, and seven of those diagnosed with bowel necrosis survived after the operation. The remaining 35 patients received conservative treatment with or without exploratory laparotomy. Between patients with and without bowel necrosis, laboratory data revealed significant differences in the levels of C-reactive protein (P = 0.0038), creatinine (P = 0.0054), and lactate (P = 0.045); clinical findings showed differences in abdominal pain (P = 0.019) and peritoneal irritation signs (P = 0.016); computed tomography detected ascites (P = 0.011) and changes of bowel wall enhancement (P = 0.03) that were significantly higher in patients with bowel necrosis. The rate of PI and/or PVG detected in patients postoperatively was significantly higher in patients with bowel necrosis (P < 0.0001). Multivariate analysis showed that bowel necrosis was significantly more likely when PI or PVG was detected in postoperative patients than in patients who had not had surgery (P = 0.003). PI and/or PVG, alone, are not automatically indicative of bowel necrosis. However, when these conditions occur postoperatively, they indicate bowel necrosis requiring reoperation.

Subclinical myocardial necrosis and cardiovascular risk in stable patients undergoing elective cardiac evaluation.

PubMed

Tang, W H Wilson; Wu, Yuping; Nicholls, Stephen J; Brennan, Danielle M; Pepoy, Michael; Mann, Shirley; Pratt, Alan; Van Lente, Frederick; Hazen, Stanley L

2010-03-01

The presence of subclinical myocardial necrosis as a prodrome to longer-term adverse cardiac event risk has been debated. The debate has focused predominantly within patients with acute coronary syndrome, and on issues of troponin assay variability and accuracy of detection, rather than on the clinical significance of the presence of subclinical myocardial necrosis (ie, "troponin leak") within stable cardiac patients. Herein, we examine the relationship between different degrees of subclinical myocardial necrosis and long-term adverse clinical outcomes within a stable cardiac patient population with essentially normal renal function. Sequential consenting patients (N=3828; median creatinine clearance, 100 mL/min/1.73m(2)) undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (<0.03 ng/mL) were evaluated. The relationship of subclinical myocardial necrosis with incident major adverse cardiovascular events (defined as any death, myocardial infarction, or stroke) over 3-year follow-up was examined. "Probable" (cTnI 0.001-0.008 ng/mL) and "definite" (cTnI 0.009-0.029 ng/mL) subclinical myocardial necrosis were observed frequently within the cohort (34% and 18%, respectively). A linear relationship was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident major adverse cardiovascular events, particularly in those with cTnI 0.009 ng/mL or higher (hazard ratio, 3.00; 95% confidence interval, 2.4-3.8), even after adjustment for traditional risk factors, C-reactive protein, and creatinine clearance. The presence of subclinical myocardial necrosis was associated with elevations in acute phase proteins (C-reactive protein, ceruloplasmin; P<0.01 each) and reduction in systemic antioxidant enzyme activities (arylesterase; P<0.01) but showed no significant associations with multiple specific measures of oxidant stress, and showed borderline

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com; Indiana University Health Proton Therapy Center, Bloomington, Indiana; Linton, Okechukwu R.

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 evaluatedmore » 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

Arsenic trioxide-induced osteo-necrosis treatment in a child: mini-review and case report.

PubMed

Marty, M; Noirrit-Esclassan, E; Diemer, F

2016-10-01

Arsenic oxide compounds were traditionally used as devitalizing agents. Due to its toxicity, leakage of such compounds into the periodontium can cause gingival and osteo-necrosis. Their use is forbidden in Europe and the USA for decades, however, some dentists seem to still use it. We report the case of a 14-year-old girl referred to the paediatric dentistry department of Toulouse University hospital, France, presenting a bone necrosis following the use of an arsenic trioxide product to accelerate pulp necrosis. The treatment included surgical removal of necrosis bone sequestrum, complete pulpectomy and an intermediate restoration of the tooth 27. After 1 week, the clinical conditions greatly improved. A restoration using a ceramic crown was performed after 2 months, and complete healing was observed after 1 year follow-up. Although arsenic trioxide is neither appropriate nor permitted for use in modern dentistry, especially in paediatric dentistry, some rare cases of arsenic-induced osteo-necrosis can still be encountered. A clearer message must be given to all dental practitioners against the use of arsenic trioxide in modern endodontic treatment.

Genetic inhibition of protein kinase Cε attenuates necrosis in experimental pancreatitis

PubMed Central

Liu, Yannan; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.

2014-01-01

Understanding the regulation of death pathways, necrosis and apoptosis, in pancreatitis is important for developing therapies directed to the molecular pathogenesis of the disease. Protein kinase Cε (PKCε) has been previously shown to regulate inflammatory responses and zymogen activation in pancreatitis. Furthermore, we demonstrated that ethanol specifically activated PKCε in pancreatic acinar cells and that PKCε mediated the sensitizing effects of ethanol on inflammatory response in pancreatitis. Here we investigated the role of PKCε in the regulation of death pathways in pancreatitis. We found that genetic deletion of PKCε resulted in decreased necrosis and severity in the in vivo cerulein-induced pancreatitis and that inhibition of PKCε protected the acinar cells from CCK-8 hyperstimulation-induced necrosis and ATP reduction. These findings were associated with upregulation of mitochondrial Bak and Bcl-2/Bcl-xL, proapoptotic and prosurvival members in the Bcl-2 family, respectively, as well as increased mitochondrial cytochrome c release, caspase activation, and apoptosis in pancreatitis in PKCε knockout mice. We further confirmed that cerulein pancreatitis induced a dramatic mitochondrial translocation of PKCε, suggesting that PKCε regulated necrosis in pancreatitis via mechanisms involving mitochondria. Finally, we showed that PKCε deletion downregulated inhibitors of apoptosis proteins, c-IAP2, survivin, and c-FLIPs while promoting cleavage/inactivation of receptor-interacting protein kinase (RIP). Taken together, our findings provide evidence that PKCε activation during pancreatitis promotes necrosis through mechanisms involving mitochondrial proapoptotic and prosurvival Bcl-2 family proteins and upregulation of nonmitochondrial pathways that inhibit caspase activation and RIP cleavage/inactivation. Thus PKCε is a potential target for prevention and/or treatment of acute pancreatitis. PMID:25035113

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

Prediction and measurement of thermally induced cambial tissue necrosis in tree stems

Treesearch

Joshua L. Jones; Brent W. Webb; Bret W. Butler; Matthew B. Dickinson; Daniel Jimenez; James Reardon; Anthony S. Bova

2006-01-01

A model for fire-induced heating in tree stems is linked to a recently reported model for tissue necrosis. The combined model produces cambial tissue necrosis predictions in a tree stem as a function of heating rate, heating time, tree species, and stem diameter. Model accuracy is evaluated by comparison with experimental measurements in two hardwood and two softwood...

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.

Imaging of endoscopic cystogastrostomy in pancreatic walled-off necrosis: what the radiologist needs to know.

PubMed

Abou Karam, Anthony; Bagherpour, Arya; Calleros, Jesus; Laks, Shaked

2018-04-04

Acute pancreatitis is a frequent entity encountered by radiologists. In 2012, the Atlanta criteria were revised to help radiologists use a common nomenclature when describing acute pancreatitis and its complications. One delayed complication of acute necrotizing pancreatitis in walled-off necrosis, a collection seen at least 4 weeks after an episode of acute pancreatic necrosis and/or acute peripancreatic necrosis. Multiple treatments have been adapted in the setting of walled-off necrosis, including endoscopic cystogastrostomy. The focus of this article is to familiarize the radiologist with the imaging appearance of this procedure as well as, review the outcomes and potential complications of endoscopic cystogastrostomy.

Risk factors for pedicled flap necrosis in hand soft tissue reconstruction: a multivariate logistic regression analysis.

PubMed

Gong, Xu; Cui, Jianli; Jiang, Ziping; Lu, Laijin; Li, Xiucun

2018-03-01

Few clinical retrospective studies have reported the risk factors of pedicled flap necrosis in hand soft tissue reconstruction. The aim of this study was to identify non-technical risk factors associated with pedicled flap perioperative necrosis in hand soft tissue reconstruction via a multivariate logistic regression analysis. For patients with hand soft tissue reconstruction, we carefully reviewed hospital records and identified 163 patients who met the inclusion criteria. The characteristics of these patients, flap transfer procedures and postoperative complications were recorded. Eleven predictors were identified. The correlations between pedicled flap necrosis and risk factors were analysed using a logistic regression model. Of 163 skin flaps, 125 flaps survived completely without any complications. The pedicled flap necrosis rate in hands was 11.04%, which included partial flap necrosis (7.36%) and total flap necrosis (3.68%). Soft tissue defects in fingers were noted in 68.10% of all cases. The logistic regression analysis indicated that the soft tissue defect site (P = 0.046, odds ratio (OR) = 0.079, confidence interval (CI) (0.006, 0.959)), flap size (P = 0.020, OR = 1.024, CI (1.004, 1.045)) and postoperative wound infection (P < 0.001, OR = 17.407, CI (3.821, 79.303)) were statistically significant risk factors for pedicled flap necrosis of the hand. Soft tissue defect site, flap size and postoperative wound infection were risk factors associated with pedicled flap necrosis in hand soft tissue defect reconstruction. © 2017 Royal Australasian College of Surgeons.

An investigation of ear necrosis in pigs.

PubMed

Park, Jeonghwa; Friendship, Robert M; Poljak, Zvonimir; DeLay, Josepha; Slavic, Durda; Dewey, Catherine E

2013-05-01

Porcine ear necrosis was investigated in 23 conveniently chosen farms, consisting of 14 case farms and 9 control farms. Biopsies of lesions and oral swabs from pigs on 11 case farms were examined by histology and bacterial culture. All farms were visited for observations and a survey on management, housing, and the presence of other clinical signs or behavioral vices. Histological examination revealed that the lesions began on the surface and progressed to deeper layers, and that vascular damage did not appear to be the initiating cause. Spirochetes were only rarely observed in histological examination and were not cultured from biopsies and oral swabs. Staphylococcus aureus and Staphylococcus hyicus were cultured from 91% and 66% of samples, respectively. Ear biting and a humid environment were associated with ear necrosis. On some farms large numbers of pigs were affected and lesions were sometimes extensive. The condition appears to be an infectious disease beginning on the surface of the skin; contributing environmental and management factors are likely.

An investigation of ear necrosis in pigs

PubMed Central

Park, Jeonghwa; Friendship, Robert M.; Poljak, Zvonimir; DeLay, Josepha; Slavic, Durda; Dewey, Catherine E.

2013-01-01

Porcine ear necrosis was investigated in 23 conveniently chosen farms, consisting of 14 case farms and 9 control farms. Biopsies of lesions and oral swabs from pigs on 11 case farms were examined by histology and bacterial culture. All farms were visited for observations and a survey on management, housing, and the presence of other clinical signs or behavioral vices. Histological examination revealed that the lesions began on the surface and progressed to deeper layers, and that vascular damage did not appear to be the initiating cause. Spirochetes were only rarely observed in histological examination and were not cultured from biopsies and oral swabs. Staphylococcus aureus and Staphylococcus hyicus were cultured from 91% and 66% of samples, respectively. Ear biting and a humid environment were associated with ear necrosis. On some farms large numbers of pigs were affected and lesions were sometimes extensive. The condition appears to be an infectious disease beginning on the surface of the skin; contributing environmental and management factors are likely. PMID:24155434

Two types of bone necrosis in the Middle Triassic Pistosaurus longaevus bones: the results of integrated studies

NASA Astrophysics Data System (ADS)

Surmik, Dawid; Rothschild, Bruce M.; Dulski, Mateusz; Janiszewska, Katarzyna

2017-07-01

Avascular necrosis, diagnosed on the basis of either a specific pathological modification of the articular surfaces of bone or its radiologic appearance in vertebral centra, has been recognized in many Mesozoic marine reptiles as well as in present-day marine mammals. Its presence in the zoological and paleontologic record is usually associated with decompression syndrome, a disease that affects secondarily aquatic vertebrates that could dive. Bone necrosis can also be caused by infectious processes, but it differs in appearance from decompression syndrome-associated aseptic necrosis. Herein, we report evidence of septic necrosis in the proximal articular surface of the femur of a marine reptile, Pistosaurus longaevus, from the Middle Triassic of Poland and Germany. This is the oldest recognition of septic necrosis associated with septic arthritis in the fossil record so far, and the mineralogical composition of pathologically altered bone is described herein in detail. The occurrence of septic necrosis is contrasted with decompression syndrome-associated avascular necrosis, also described in Pistosaurus longaevus bone from Middle Triassic of Germany.

Autologous Platelet Concentrates as Treatment for Avascular Necrosis of Femoral Head in a Dog.

PubMed

Parra, Estefanía; Vergara, Andrea; Silva, Raúl F

2017-03-01

Avascular necrosis of the femoral head is a developmental disturbance that generally affects young dogs of small breeds and produces ischemic necrosis of the femoral head resulting in an incongruous and malformed joint. The most common treatment is the excisional arthroplasty of the head and femoral neck. The aim of this study is to describe the treatment of avascular necrosis in a Yorkshire dog using intra-articular injections of autologous platelet concentrate. Evaluations were made at 0, 15, 30, 60, and 120 days of treatment, describing the following parameters: clinical gait analysis, perimetry, goniometry, and radiographic evaluations. The results obtained in this case suggest that the autologous platelet concentrate may be an alternative for the treatment of avascular necrosis of the femoral head in dogs. Copyright © 2017 Elsevier Inc. All rights reserved.

Late temporal lobe necrosis after conventional radiotherapy for carcinoma of maxillary sinus.

PubMed

Kanakamedala, Madhava R; Mahta, Ali; Liu, Jianlin; Kesari, Santosh

2012-12-01

Cerebral radiation necrosis is a serious late complication after conventional radiotherapy that can present with focal neurologic deficits or with more generalized signs and symptoms of increased intracranial pressure, depending on the location. The incidence and severity of radionecrosis are dose-volume dependent. We report a case of cerebral radiation necrosis 5 years after radiotherapy for a maxillary sinus carcinoma.

Submassive hepatic necrosis induced by dichloropropanol.

PubMed

Haratake, J; Furuta, A; Iwasa, T; Wakasugi, C; Imazu, K

1993-06-01

A hitherto undescribed industrial liver injury of fulminant form induced by dichloropropanol is reported. Two middle-aged men developed severe hepatic injury just after cleaning a dichloropropanol tank at a plant producing dichloropropanol. They died from hepatic failure 4 and 11 days respectively, after carrying out the work. Liver specimens taken at autopsy from one of the cases showed submassive hepatic necrosis. This accident prompted us to undertake an experimental study in rats of intraperitoneal one-shot injection of two isomeric substances of dichloropropanol, that is, 2,3-dichloro-1-propanol (DC1P) and 1,3-dichloro-2-propanol (DC2P). Saline was injected into the control rats. One, two, four, six, 24, 48, 72 h, and 1 week after the injection, rats in each group were sacrificed. Neither control nor DC1P-injected rats showed significant biochemical or histopathological abnormalities. DC2P-injected rats revealed elevations of transaminase from 6 h after the injections, and submassive necrosis of the liver was observed in many rats. It was concluded that the severe liver injuries in both the human cases and rats in our study were caused by DC2P.

Spontaneous and bilateral avascular necrosis of the navicula: Müller-Weiss disease.

PubMed

Aktaş, Erdem; Ayanoğlu, Tacettin; Hatipoğlu, Yasin; Kanatlı, Ulunay

2016-12-01

Although, trauma, foot deformity (pesplanovalgus), systemic diseases such as diabetes mellitus and lupus, drugs (steroids, antineoplastic) and excessive alcohol consumption have all been accused in the etiology of avascular necrosis of the tarsal bones, spontaneous avascular necrosis of the navicular bone, especially in adults, is a rare entity. In this article, we report a 50-year-old female patient with bilateral, spontaneous avascular necrosis of the navicular bone and related severe talonavicular arthrosis. Clinical and radiological findings were concordant with Müller-Weiss disease, which is a rare disease with complex idiopathic foot condition of the adult tarsal navicular bone characterized by progressive navicular fragmentation and talonavicular joint destruction. The patient was successfully treated with two-staged bilateral talonavicular arthrodesis.

[Novel Anticancer Strategy Targeting Switch Mechanisms in Two Types of Cell Death: Necrosis and Apoptosis].

PubMed

Sato, Akira

2017-01-01

 Two types of cell death, necrosis and apoptosis, are defined in terms of cell death morphological features. We have been studying the mechanisms by which cell death processes are switched during the treatment of mouse tumor FM3A with anticancer, 5-fluoro-2'-deoxyuridine (FUdR): it induces original clone F28-7 to necrosis, but its sub-clone F28-7-A to apoptosis. We identified several such switch regulators of cell death: heat shock protein 90 (HSP90), lamin-B1, cytokeratin-19, and activating transcription factor 3 (ATF3), by using transcriptomic, proteomic analyses and siRNA screening. For example, the inhibition of HSP90 by its inhibitor geldanamycin in F28-7 caused a shift from necrosis to apoptosis. We also observed that the knockdown of lamin-B1, cytokeratin-19, or ATF3 expression in F28-7 resulted in a shift from necrosis to apoptosis. Recently, we used microRNA (miRNA, miR) microarray analyses to investigate the miRNA expression profiles in these sister cells. The miR-351 and miR-743a were expressed at higher levels in F28-7-A than in F28-7. Higher expression of miR-351 or miR-743a in F28-7, induced by transfecting the miR mimics, resulted in a switch of cell death mode: necrosis to apoptosis. Furthermore, transfection of an miR-351 inhibitor into F28-7-A resulted in morphological changes, and mode of cell death from apoptosis to necrosis. These findings suggest that the identified cell death regulators may have key roles in switching cell death mode. Possible mechanisms involving cell death regulators in the switch of necrosis or apoptosis are discussed. We propose a novel anticancer strategy targeting the switch regulators of necrosis or apoptosis.

[Gender analysis among articles published in Enfermedades Infecciosas y Microbiología Clínica (2001-2005)].

PubMed

Aleixandre-Benavent, Rafael; González-Alcaide, Gregorio; Alonso-Arroyo, Adolfo; Castellano-Gómez, Miguel; Valderrama-Zurián, Juan Carlos

2007-12-01

There is growing concern for promoting equality between sexes and full integration of women in research activities. The purpose of this study is to identify the bibliometric characteristics of articles published during the 2001-2005 period in Enfermedades Infecciosas y Microbiología Clínica (EIMC) from the perspective of gender. EIMC records for 2001-2005 were obtained from the Science Citation Index database and differences according to sex were calculated for the following indicators: year of publication, type of document, number and order of author signatures, number of collaborators, and the signature/article index at the institutional and geographical level. A total of 2,163 authors were identified, 1,220 (56.4%) men and 943 (43.6%) women. The greatest of contribution from women was in original articles (42.32% of signatures). Excluding the Centro Nacional de Microbiología (Spanish National Center for Microbiology), the participation of women was lower than men in the most productive institutions. There were significant differences regarding the number of papers published and the number of collaborators; with greater productivity for men and a higher rate of collaboration for women. Studies on scientific activity according to gender provide essential information to establish the basis for a policy of equality in this regard. A yearly increase of almost 1% was seen in the number of female authors contributing articles to the EIMC, which, if the trend continues, will result in parity in coming years. Nevertheless, the presence of women in positions of high productivity remains low. The causes of this difference should be identified and corrected.

Fat necrosis after abdominal surgery: A pitfall in interpretation of FDG-PET/CT.

PubMed

Davidson, Tima; Lotan, Eyal; Klang, Eyal; Nissan, Johnatan; Goldstein, Jeffrey; Goshen, Elinor; Ben-Haim, Simona; Apter, Sara; Chikman, Bar

2018-06-01

We describe FDG-PET/CT findings of postoperative fat necrosis in patients following abdominal surgery, and evaluate their changes in size and FDG uptake over time. FDG-PET/CT scans from January 2007-January 2016 containing the term 'fat necrosis' were reviewed. Lesions meeting radiological criteria of fat necrosis in patients with prior abdominal surgery were included. Forty-four patients, 30 males, mean age 68.4 ± 11.0 years. Surgeries: laparotomy (n=37; 84.1 %), laparoscopy (n=3; 6.8 %), unknown (n=4; 9.1 %). CTs of all lesions included hyperdense well-defined rims surrounding a heterogeneous fatty core. Sites: peritoneum (n=34; 77 %), omental fat (n=19; 43 %), subcutaneous fat (n=8; 18 %), retroperitoneum (n=2; 5 %). Mean lesion long axis: 33.6±24.9 mm (range: 13.0-140.0). Mean SUVmax: 2.6±1.1 (range: 0.6-5.1). On serial CTs (n=34), lesions decreased in size (p=0.022). Serial FDG-PET/CT (n=24) showed no significant change in FDG-avidity (p=0.110). Mean SUVmax did not correlate with time from surgery (p=0.558) or lesion size (p=0.259). Postsurgical fat necrosis demonstrated characteristic CT features and may demonstrate increased FDG uptake. However, follow-up of subsequent imaging scans showed no increases in size or FDG-avidity. Awareness of this entity is important to avoid misinterpretation of findings as recurrent cancer. • Postsurgical fat necrosis may mimic cancer in FDG-PET/CT. • Follow-up of fat necrosis showed no increase in FDG intensity. • CT follow-up showed a decrease in lesion size. • FDG uptake did not correlate with time lapsed from surgery.

Oxidative stress and cardiomyocyte necrosis with elevated serum troponins: pathophysiologic mechanisms.

PubMed

Robinson, Antwon D; Ramanathan, Kodangudi B; McGee, Jesse E; Newman, Kevin P; Weber, Karl T

2011-08-01

The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca accumulation and mitochondria Ca overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.

Thermal isotherms in PMMA and cell necrosis during total hip arthroplasty.

PubMed

Gundapaneni, Dinesh; Goswami, Tarun

2014-12-30

Polymethylmethacrylate (PMMA), also known as bone cement, is a commonly used adhesive material to fix implants in Total Hip Arthroplasty (THA). During implantation, bone cement undergoes a polymerization reaction which is an exothermic reaction and results in the release of heat to the surrounding bone tissue, which ultimately leads to thermal necrosis. Necrosis in the bony tissue results in early loosening of the implant, which causes pain and reduces the life of the implant. The main objective of the present study was to understand the thermal isotherms in PMMA and to determine the optimal cement mantle thickness to prevent cell necrosis during THA. In this study, the environment in the bony tissue during implantation was simulated by constructing 3D solid models to observe the temperature distribution in the bony tissue at different cement mantle thicknesses (1 mm, 3 mm and 5 mm), by applying the temperature conditions that exist during the surgery. Stems made with Co-Cr-Mo, 316L stainless steel and Ti6Al4V were used, which acted as heat sinks, and a thermal damage equation was used to measure the bone damage. FEA was conducted based on temperature conditions and thermal isotherms at different cement mantle thicknesses were obtained. Thermal isotherms derived with respect to distance in the bony tissue from the center of the cement mantle, and cell necrosis was determined at different mantle thicknesses. Based on the deduced results, cement mantle thickness of 1-5 mm does not cause thermal damage in the bony tissue. Considering the long term stability of the implant, cement mantle thickness range from 3 mm-5 mm was found to be optimal in THA to prevent cell necrosis.

[Programmed necrosis mediated by receptor-interacting protein 3: a new target for liver disease research].

PubMed

Zhang, J; Jing, Y; Li, Y N; Zhou, L; Wang, B M

2016-09-20

Hepatocyte death mainly includes apoptosis and necrosis and is a critical process in the pathophysiological mechanism of liver injury caused by various reasons. Recent studies have shown that key regulatory molecules in the inhibition of apoptosis such as caspase cannot be used as targets for inhibiting disease progression in clinical practice. In recent years, programmed necrosis mediated by receptor-interacting protein 3(RIP3)becomes a new hot research topic. It not only plays an important role in inducing inflammatory response, but also is closely regulated by intracellular signal factors, and it is a type of active cell death which can be interfered with. Compared with apoptosis, programmed necrosis is accompanied by the release of various inflammatory factors, which significantly affects local immune microenvironment. RIP3-mediated programmed necrosis has been taken seriously in many diseases. Although its mechanism of action in liver disease remains unclear, the results of recent studies confirmed its important role in the development of liver disease. This article reviews the research advances in the role of RIP3-mediated programmed necrosis signaling pathway in liver disease of various causes and investigates the possibility of RIP3-mediated programmed necrosis as a new target in the treatment of liver disease.

Spermidine rescues proximal tubular cells from oxidative stress and necrosis after ischemic acute kidney injury.

PubMed

Kim, Jinu

2017-10-01

Kidney ischemia and reperfusion injury (IRI) is associated with a high mortality rate, which is attributed to tubular oxidative stress and necrosis; however, an effective approach to limit IRI remains elusive. Spermidine, a naturally occurring polyamine, protects yeast cells against aging through the inhibition of oxidative stress and necrosis. In the present study, spermidine supplementation markedly attenuated increases in plasma creatinine concentration and tubular injury score after IRI. In addition, exogenous spermidine potently inhibited oxidative stress, especially lipid peroxidation after IRI in kidneys and exposure to hydrogen peroxide in kidney proximal tubular cells, suppressing plasma membrane disruption and necrosis. Consistent with spermidine supplementation, upregulation of ornithine decarboxylase (ODC) in human kidney proximal tubular cells significantly diminished lipid peroxidation and necrosis induced by hydrogen peroxide-induced injury. Conversely, ODC deficiency significantly enhanced lipid peroxidation and necrosis after exposure to hydrogen peroxide. Finally, small interfering RNA-mediated ODC inhibition induced functional and histological damage in kidneys as well as it increased lipid hydroperoxide levels after IRI. In conclusion, these data suggest that spermidine level determines kidney proximal tubular damage through oxidative stress and necrosis induced by IRI, and this finding provides a novel target for prevention of tubular damage induced by IRI.

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. Copyright © 2015. Published by Elsevier B.V.

Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma

PubMed Central

Pejnovic, Nada N.; Mitrovic, Slobodanka L. J.; Arsenijevic, Nebojsa N.; Simovic Markovic, Bojana J.; Lukic, Miodrag L.

2016-01-01

Interleukin-33 (IL-33)/IL-33 receptor (IL-33R, ST2) signaling pathway promotes mammary cancer growth and metastasis by inhibiting anti-tumor immunity. However, the role of IL-33/IL-33R axis in neoangiogenesis and tumor necrosis is not elucidated. Therefore, the aim of this study was to investigate the role of IL-33/IL-33R axis in mammary tumor necrosis. Deletion of IL-33R (ST2) gene in BALB/c mice enhanced tumor necrosis and attenuated tumor growth in 4T1 breast cancer model, which was associated with markedly decreased expression of vascular endothelial growth factor (VEGF) and IL-33 in mammary tumor cells. We next analyzed IL-33, IL-33R and VEGF expression and microvascular density (MVD) in breast tumors from 40 female patients with absent or present tumor necrosis. We found significantly higher expression of IL-33, IL-33R and VEGF in breast cancer tissues with absent tumor necrosis. Both, IL-33 and IL-33R expression correlated with VEGF expression in tumor cells. Further, VEGF expression positively correlated with MVD in perinecrotic zone. Taking together, our data indicate that IL-33/IL-33R pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGF in tumor cells and attenuating tumor necrosis. These data add an unidentified mechanism by which IL-33/IL-33R axis facilitates tumor growth. PMID:26919112

Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma.

PubMed

Milosavljevic, Milos Z; Jovanovic, Ivan P; Pejnovic, Nada N; Mitrovic, Slobodanka L J; Arsenijevic, Nebojsa N; Simovic Markovic, Bojana J; Lukic, Miodrag L

2016-04-05

Interleukin-33 (IL-33)/IL-33 receptor (IL-33R, ST2) signaling pathway promotes mammary cancer growth and metastasis by inhibiting anti-tumor immunity. However, the role of IL-33/IL-33R axis in neoangiogenesis and tumor necrosis is not elucidated. Therefore, the aim of this study was to investigate the role of IL-33/IL-33R axis in mammary tumor necrosis. Deletion of IL-33R (ST2) gene in BALB/c mice enhanced tumor necrosis and attenuated tumor growth in 4T1 breast cancer model, which was associated with markedly decreased expression of vascular endothelial growth factor (VEGF) and IL-33 in mammary tumor cells. We next analyzed IL-33, IL-33R and VEGF expression and microvascular density (MVD) in breast tumors from 40 female patients with absent or present tumor necrosis. We found significantly higher expression of IL-33, IL-33R and VEGF in breast cancer tissues with absent tumor necrosis. Both, IL-33 and IL-33R expression correlated with VEGF expression in tumor cells. Further, VEGF expression positively correlated with MVD in perinecrotic zone. Taking together, our data indicate that IL-33/IL-33R pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGF in tumor cells and attenuating tumor necrosis. These data add an unidentified mechanism by which IL-33/IL-33R axis facilitates tumor growth.

Carrot yellow leaf virus is associated with carrot internal necrosis.

PubMed

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.

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

The role of tumour necrosis factor alpha and soluble tumour necrosis factor alpha receptors in the symptomatology of schizophrenia.

PubMed

Turhan, Levent; Batmaz, Sedat; Kocbiyik, Sibel; Soygur, Arif Haldun

2016-07-01

Background Immunological mechanisms may be responsible for the development and maintenance of schizophrenia symptoms. Aim The aim of this study is to measure tumour necrosis factor-alpha (TNF-α), soluble tumour necrosis factor-alpha receptor I (sTNF-αRI), and soluble tumour necrosis factor-alpha receptor II (sTNF-αRII) levels in patients with schizophrenia and healthy individuals, and to determine their relationship with the symptoms of schizophrenia. Methods Serum TNF-α, sTNF-αRI and sTNF-αRII levels were measured. The Positive and Negative Syndrome Scale (PANSS) was administered for patients with schizophrenia (n = 35), and the results were compared with healthy controls (n = 30). Hierarchical regression analyses were undertaken to predict the levels of TNF-α, sTNF-αRI and sTNF-αRII. Results No significant difference was observed in TNF-α levels, but sTNF-αRI and sTNF-αRII levels were lower in patients with schizophrenia. Serum sTNF-αRI and sTNF-αRII levels were found to be negatively correlated with the negative subscale score of the PANSS, and sTNF-αRI levels were also negatively correlated with the total score of the PANSS. Smoking, gender, body mass index were not correlated with TNF-α and sTNF-α receptor levels. Conclusions These results suggest that there may be a change in anti-inflammatory response in patients with schizophrenia due to sTNF-αRI and sTNF-αRII levels. The study also supports low levels of TNF activity in schizophrenia patients with negative symptoms.

MRI Brain Tumor Segmentation and Necrosis Detection Using Adaptive Sobolev Snakes.

PubMed

Nakhmani, Arie; Kikinis, Ron; Tannenbaum, Allen

2014-03-21

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 different 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 diffusion 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.

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.

Diagnostic ultrasonography in cattle with abdominal fat necrosis.

PubMed

Tharwat, Mohamed; Buczinski, Sébastien

2012-01-01

This study describes the ultrasonographic findings in 14 cows with abdominal fat necrosis. Ultrasonography of the abdomen revealed the presence of heterogeneous hyperechoic masses and hyperechoic omentum with localized masses floating in a hypoechoic peritoneal fluid. A hyperechogenic rim was imaged around both kidneys. The intestines were coated with hyperechoic capsules and the intestinal lumens were constricted. Ultrasonographic examination of the pancreatic parenchyma showed an overall increased echogenicity which was homogenously distributed in 3 cases. A diagnosis of abdominal fat necrosis was made with ultrasound-guided biopsy of the echogenic masses, and thereafter at postmortem examination. Results from this study demonstrate the efficacy of ultrasonography as an imaging modality for antemortem diagnosis of abdominal lipomatosis in cattle. To the authors' knowledge, this study is the first that illustrates ultrasonographic findings in cattle affected with abdominal lipomatosis.

Conservative treatment of sickle cell avascular necrosis of the femoral head.

PubMed

Washington, E R; Root, L

1985-01-01

Treatment of avascular necrosis of the femoral head in adolescents with sickle cell anemia has not yet been standardized. In this study we review the literature and report on three patients with the Legg-Perthes-type avascular necrosis associated with sickle cell disease. These patients were successfully treated by partial weight-bearing with crutches and active range-of-motion exercises. We have examined physiologic and anatomic factors in this specific disease syndrome, which suggest that this may be the preferred method of treatment.

Managing Necrosis of the Nipple Areolar Complex Following Reduction Mammaplasty and Mastopexy.

PubMed

Handel, Neal; Yegiyants, Sara

2016-04-01

The objectives of this article are to explain the mechanisms of injury that result in ischemia of the nipple areolar complex (NAC) after reduction mammaplasty or mastopexy, to offer recommendations about the management of this complication, and to illustrate reconstructive techniques that can be used to correct deformities arising from necrosis of the NAC. With these goals in mind, the article is divided into 3 sections: prevention of ischemia of the NAC, management of the ischemic nipple, and reconstruction after ischemic necrosis of the nipple and areola. Necrosis of all or part of the NAC is a devastating complication after breast surgery. However, with properly timed and well-executed reconstructive procedures, it is possible in most cases to restore a natural-appearing NAC. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel biomarker identification using metabolomic profiling to differentiate radiation necrosis and recurrent tumor following Gamma Knife radiosurgery.

PubMed

Lu, Alex Y; Turban, Jack L; Damisah, Eyiyemisi C; Li, Jie; Alomari, Ahmed K; Eid, Tore; Vortmeyer, Alexander O; Chiang, Veronica L

2017-08-01

OBJECTIVE Following an initial response of brain metastases to Gamma Knife radiosurgery, regrowth of the enhancing lesion as detected on MRI may represent either radiation necrosis (a treatment-related inflammatory change) or recurrent tumor. Differentiation of radiation necrosis from tumor is vital for management decision making but remains difficult by imaging alone. In this study, gas chromatography with time-of-flight mass spectrometry (GC-TOF) was used to identify differential metabolite profiles of the 2 tissue types obtained by surgical biopsy to find potential targets for noninvasive imaging. METHODS Specimens of pure radiation necrosis and pure tumor obtained from patient brain biopsies were flash-frozen and validated histologically. These formalin-free tissue samples were then analyzed using GC-TOF. The metabolite profiles of radiation necrosis and tumor samples were compared using multivariate and univariate statistical analysis. Statistical significance was defined as p ≤ 0.05. RESULTS For the metabolic profiling, GC-TOF was performed on 7 samples of radiation necrosis and 7 samples of tumor. Of the 141 metabolites identified, 17 (12.1%) were found to be statistically significantly different between comparison groups. Of these metabolites, 6 were increased in tumor, and 11 were increased in radiation necrosis. An unsupervised hierarchical clustering analysis found that tumor had elevated levels of metabolites associated with energy metabolism, whereas radiation necrosis had elevated levels of metabolites that were fatty acids and antioxidants/cofactors. CONCLUSIONS To the authors' knowledge, this is the first tissue-based metabolomics study of radiation necrosis and tumor. Radiation necrosis and recurrent tumor following Gamma Knife radiosurgery for brain metastases have unique metabolite profiles that may be targeted in the future to develop noninvasive metabolic imaging techniques.

Tumour necrosis factor-α and risk of cardiovascular disease among overfat Indonesian adolescents.

PubMed

Sulistyoningrum, Dian Caturini; Susilowati, Rina; Huriyati, Emy; Witari, Ni Putu Diah; Luglio, Harry Freitag; Julia, Madarina

2017-06-01

Overfatness (overweight and obesity) is associated with an increased risk of cardiovascular disease, including elevated blood pressure, dyslipidaemia, and insulin resistance. Chronic inflammation may play a role in mediating these associations. To investigate the association between plasma tumour necrosis factor-α and risk factors for cardiovascular disease among overweight and obese adolescents. This study was an observational analysis with a cross-sectional design for high school students in Yogyakarta, Indonesia. One hundred and fifteen overweight and obese adolescents (mean age 16.8 years; 48.3% female) were involved in the study. Overfatness was specified by body mass index z-scores. Anthropometric measurements, blood pressure, lipid profiles, and fasting glucose were obtained. Fasting plasma insulin and plasma tumour necrosis factor-α were quantified using enzyme-linked immunosorbent assay. Insulin resistance was represented as the homeostatic model assessment value. Data were analysed using SPSS for Windows, version 23. Plasma tumour necrosis factor-α was significantly associated with total cholesterol (p=0.046) and diastolic blood pressure (p=0.018) among the overweight and obese adolescents. Results from path analyses showed that there were indirect effects of z-score BMI on systolic and diastolic blood pressures, HDL and fasting plasma glucose mediated by plasma tumour necrosis factor-α concentrations. Meanwhile, there were indirect effects of waist circumference on systolic and diastolic blood pressure by age and height percentile and HDL. There was no significant association between plasma tumour necrosis factor-α and insulin resistance. The study showed that a proinflammatory marker, plasma tumour necrosis factor-α, is associated with blood pressure, HDL and fasting plasma glucose in overweight and obese adolescents. This indicates that inflammation in overweight and obesity may play a role in increasing the risk of cardiovascular disease.

Correlation between electrical conductivity and apparent diffusion coefficient in breast cancer: effect of necrosis on magnetic resonance imaging.

PubMed

Kim, Soo-Yeon; Shin, Jaewook; Kim, Dong-Hyun; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; You, Jai Kyung; Kim, Min Jung

2018-03-06

To investigate the correlation between conductivity and ADC in invasive ductal carcinoma according to the presence of necrosis on MRI. Eighty-one women with invasive ductal carcinoma ≥1 cm on T2-weighted fast spin echo sequence of preoperative MRI were included. Phase-based MR electric properties tomography was used to reconstruct conductivity. Mean ADC was measured. Necrosis was defined as an area with very high T2 signal intensity. The relationship between conductivity and ADC was examined using Spearman's correlation coefficient (r). Multiple linear regression analysis was performed to identify factors associated with conductivity or ADC. In the total group, conductivity showed negative correlation with ADC (r = -0.357, p = 0.001). This correlation was maintained in the subgroup without necrosis (n = 53, r = -0.455, p = 0.001), but not in the subgroup with necrosis (n = 28, r = -0.080, p = 0.687). The correlation between the two parameters was different according to necrosis (r = -0.455 vs -0.080, p = 0.047). HER2 enriched subtype was independently associated with conductivity (p = 0.029). Necrosis on MRI was independently associated with ADC (p = 0.027). Conductivity shows negative correlation with ADC that is abolished by the presence of necrosis on MRI. • Electric conductivity showed negative correlation with ADC • However, the correlation was abolished by the presence of necrosis on MRI • HER2-enriched subtype was independently associated with conductivity • Necrosis on MRI was independently associated with ADC.

Tumor necrosis is an important hallmark of aggressive endometrial cancer and associates with hypoxia, angiogenesis and inflammation responses

PubMed Central

Stefansson, Ingunn M.; Birkeland, Even; Bø, Trond Hellem; Øyan, Anne M.; Trovik, Jone; Kalland, Karl-Henning; Jonassen, Inge; Salvesen, Helga B.; Wik, Elisabeth; Akslen, Lars A.

2015-01-01

Aims Tumor necrosis is associated with aggressive features of endometrial cancer and poor prognosis. Here, we investigated gene expression patterns and potential treatment targets related to presence of tumor necrosis in primary endometrial cancer lesions. Methods and Results By DNA microarray analysis, expression of genes related to tumor necrosis reflected multiple tumor-microenvironment interactions like tissue hypoxia, angiogenesis and inflammation pathways. A tumor necrosis signature of 38 genes and a related patient cluster (Cluster I, 67% of the cases) were associated with features of aggressive tumors such as type II cancers, estrogen receptor negative tumors and vascular invasion. Further, the tumor necrosis signature was increased in tumor cells grown in hypoxic conditions in vitro. Multiple genes with increased expression are known to be activated by HIF1A and NF-kB. Conclusions Our findings indicate that the presence of tumor necrosis within primary tumors is associated with hypoxia, angiogenesis and inflammation responses. HIF1A, NF-kB and PI3K/mTOR might be potential treatment targets in aggressive endometrial cancers with presence of tumor necrosis. PMID:26485755

Tumor necrosis is an important hallmark of aggressive endometrial cancer and associates with hypoxia, angiogenesis and inflammation responses.

PubMed

Bredholt, Geir; Mannelqvist, Monica; Stefansson, Ingunn M; Birkeland, Even; Bø, Trond Hellem; Øyan, Anne M; Trovik, Jone; Kalland, Karl-Henning; Jonassen, Inge; Salvesen, Helga B; Wik, Elisabeth; Akslen, Lars A

2015-11-24

Tumor necrosis is associated with aggressive features of endometrial cancer and poor prognosis. Here, we investigated gene expression patterns and potential treatment targets related to presence of tumor necrosis in primary endometrial cancer lesions. By DNA microarray analysis, expression of genes related to tumor necrosis reflected multiple tumor-microenvironment interactions like tissue hypoxia, angiogenesis and inflammation pathways. A tumor necrosis signature of 38 genes and a related patient cluster (Cluster I, 67% of the cases) were associated with features of aggressive tumors such as type II cancers, estrogen receptor negative tumors and vascular invasion. Further, the tumor necrosis signature was increased in tumor cells grown in hypoxic conditions in vitro. Multiple genes with increased expression are known to be activated by HIF1A and NF-kB. Our findings indicate that the presence of tumor necrosis within primary tumors is associated with hypoxia, angiogenesis and inflammation responses. HIF1A, NF-kB and PI3K/mTOR might be potential treatment targets in aggressive endometrial cancers with presence of tumor necrosis.

Penile necrosis secondary to purpura fulminans: a case report and review of literature.

PubMed

Hogarth, David B; Cheon, Paul M; Kassam, Javeed; Seal, Alexander E; Kavanagh, Alexander G

2017-02-01

We report the case of a 60-year-old Hispanic male with widespread necrotic purpuric lesions involving the penile, suprapubic, inguinal and hip dermis due to purpura fulminans. Purpura fulminans describes a rare syndrome involving intravascular thrombosis and hemorrhagic infarction of the skin; this rapidly progressing syndrome features vascular collapse and disseminated intravascular coagulation. This patient's penile necrosis involved the majority of the penile shaft and glans penis, and ultimately required partial glansectomy and repeated debridement for treatment. Subsequently, full thickness skin grafting was completed for reconstruction with good effect. While reports of penile necrosis secondary to various causes are documented in the literature, no prior reports describe penile necrosis secondary to purpura fulminans.

Penile necrosis secondary to purpura fulminans: a case report and review of literature

PubMed Central

Cheon, Paul M.; Kassam, Javeed; Seal, Alexander E.; Kavanagh, Alexander G.

2017-01-01

Abstract We report the case of a 60-year-old Hispanic male with widespread necrotic purpuric lesions involving the penile, suprapubic, inguinal and hip dermis due to purpura fulminans. Purpura fulminans describes a rare syndrome involving intravascular thrombosis and hemorrhagic infarction of the skin; this rapidly progressing syndrome features vascular collapse and disseminated intravascular coagulation. This patient’s penile necrosis involved the majority of the penile shaft and glans penis, and ultimately required partial glansectomy and repeated debridement for treatment. Subsequently, full thickness skin grafting was completed for reconstruction with good effect. While reports of penile necrosis secondary to various causes are documented in the literature, no prior reports describe penile necrosis secondary to purpura fulminans. PMID:28479975

Nonanaplastic follicular cell-derived thyroid carcinoma: mitosis and necrosis in long-term follow-up.

PubMed

Skansing, Daniel Bräuner; Londero, Stefano Christian; Asschenfeldt, Pia; Larsen, Stine Rosenkilde; Godballe, Christian

2017-06-01

Nonanaplastic follicular cell-derived thyroid carcinoma (NAFCTC) includes differentiated- (DTC) and poorly differentiated thyroid carcinoma (PDTC). DTC has an excellent prognosis, while PDTC is situated between DTC and anaplastic carcinomas. Short-term studies suggest that PDTC patients diagnosed only on tumor necrosis and/or mitosis have a prognosis similar to those diagnosed according to the TURIN proposal. The purpose of this study was to evaluate prognosis for NAFCTC based on long-term follow-up illuminating the significance of tumor necrosis and mitosis. A cohort of 225 patients with NAFCTC was followed more than 20 years. Age, sex, distant metastasis, histology, tumor size, extrathyroidal invasion, lymph node metastasis, tumor necrosis and mitosis were examined as possible prognostic factors. Median follow-up time for patients alive was 28 years (range 20-43 years). Age, distant metastasis, extrathyroidal invasion, tumor size, tumor necrosis and mitosis were independent prognostic factors in multivariate analysis for overall survival (OS). In disease specific survival (DSS) age was not significant. Using only necrosis and/or mitosis as criteria for PDTC the 5-, 10- and 20-year OS for DTC was 87, 79 and 69%, respectively. In DSS it was 95, 92 and 90%. For PDTC the 5-, 10- and 20-year OS was 57, 40 and 25%, respectively. In DSS it was 71, 55 and 48%. Tumor necrosis and mitosis are highly significant prognostic indicators in analysis of long time survival of nonanaplastic follicular cell-derived thyroid carcinoma indicating that a simplification of the actually used criteria for poorly differentiated carcinomas may be justified.

Novel allelic variants in ACD6 cause hybrid necrosis in local collection of Arabidopsis thaliana.

PubMed

Świadek, Magdalena; Proost, Sebastian; Sieh, Daniela; Yu, Jing; Todesco, Marco; Jorzig, Christian; Rodriguez Cubillos, Andrés Eduardo; Plötner, Björn; Nikoloski, Zoran; Chae, Eunyoung; Giavalisco, Patrick; Fischer, Axel; Schröder, Florian; Kim, Sang-Tae; Weigel, Detlef; Laitinen, Roosa A E

2017-01-01

Hybrid necrosis is a common type of hybrid incompatibility in plants. This phenomenon is caused by deleterious epistatic interactions, resulting in spontaneous activation of plant defenses associated with leaf necrosis, stunted growth and reduced fertility in hybrids. Specific combinations of alleles of ACCELERATED CELL DEATH 6 (ACD6) have been shown to be a common cause of hybrid necrosis in Arabidopsis thaliana. Increased ACD6 activity confers broad-spectrum resistance against biotrophic pathogens but reduces biomass production. We generated 996 crosses among individuals derived from a single collection area around Tübingen (Germany) and screened them for hybrid necrosis. Necrotic hybrids were further investigated by genetic linkage, amiRNA silencing, genomic complementation and metabolic profiling. Restriction site associated DNA (RAD)-sequencing was used to understand genetic diversity in the collection sites containing necrosis-inducing alleles. Novel combinations of ACD6 alleles found in neighbouring stands were found to activate the A. thaliana immune system. In contrast to what we observed in controlled conditions, necrotic hybrids did not show reduced fitness in the field. Metabolic profiling revealed changes associated with the activation of the immune system in ACD6-dependent hybrid necrosis. This study expands our current understanding of the active role of ACD6 in mediating trade-offs between defense responses and growth in A.  thaliana. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Spontaneous complete necrosis of advanced hepatocellular carcinoma.

PubMed

Yokoyama, Tadashi; Yoshida, Hiroshi; Hirakata, Atsushi; Makino, Hiroshi; Maruyama, Hiroshi; Suzuki, Seiji; Matsutani, Takeshi; Hayakawa, Tomohiro; Hosone, Masaru; Uchida, Eiji

2012-01-01

We present a rare case of hepatocellular carcinoma (HCC) in which spontaneous complete necrosis was confirmed with surgical resection. An 80-year-old man with HCC was referred to Nippon Medical School Tama Nagayama Hospital. The medical history included hypertension, managed with medication, and partial lobectomy of the lung owing to a lung schwannoma. A previously untreated abdominal aortic aneurysm, 51 mm in maximum diameter, was detected. The serum concentration of proteins induced by vitamin k antagonism or absence (PIVKA-2) was 14,300 mAU/mL, and that of alpha-fetoprotein was 184.2 ng/mL. Antibodies against hepatitis B surface antigens and hepatitis C virus were not detected in the serum. Computed tomography (CT) demonstrated a hypervascular tumor, 68 mm in diameter, in the left paramedian sector of the liver with washout of contrast medium in the delayed phase. An HCC in the left paramedian sector was diagnosed. Laparotomy was performed 40 days after CT scanning. Intraoperative ultrasonography showed that the HCC had shrunk to 30 mm in diameter. A left paramedian sectionectomy was performed. On macroscopic examination the surgical specimen was a firm mass, 30 mm in diameter, with a fibrous capsule. Histologic examination showed that the tumor in the cirrhotic liver had been completely replaced by central coagulative necrosis, circumferential fibrosis, and dense infiltrates of inflammatory cells. No viable HCC cells were observed in the coagulative necrosis. Organized thrombi in the hepatic artery were detected in the tumor. The tumor also contained multiple foci of old hemorrhage, ductular proliferation, and granulation tissue. The patient was discharged 10 days after the operation. After 1 month, the serum concentrations of PIVKA-2 (25 mAU/mL) and alpha-fetoprotein (5.9 ng/mL) had decreased to within their normal ranges.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joskin, Julien, E-mail: j.joskin@gmail.com; Baere, Thierry de, E-mail: Thierry.DEBAERE@igr.fr; Auperin, Anne, E-mail: Anne.AUPERIN@igr.fr

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 developedmore » 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.« less

Avascular Necrosis in the Contralateral Hip in Patients With Congenital Femoral Deficiency: A Report of 3 Cases.

PubMed

Brown, Timothy S; Wimberly, Robert L; Birch, John G

2017-01-01

Congenital femoral deficiency is an uncommon clinical entity. We report 3 patients who developed avascular necrosis of the hip in the long (normal) leg during longitudinal observation and/or treatment of congenital femoral deficiency. Patients were identified in limb length discrepancy clinic and their charts were retrospectively reviewed for clinical and radiographic data collection. We describe the occurrence of idiopathic avascular necrosis in the normal limb in patients being followed for limb length discrepancy. Although no conclusion could be drawn about the etiology of the avascular necrosis, we describe a previously undocumented relationship between congenital femoral deficiency and avascular necrosis in the contralateral hip. This occurred in our congenital femoral deficiency population at a rate higher than expected compared with published incidences of avascular necrosis of the hip in children. Level IV-case series.

[Extensive digital necrosis during dermatomyositis associated with MDA-5 antibodies].

PubMed

Charbit, L; Bursztejn, A-C; Mohamed, S; Kaminsky, P; Lerondeau, B; Barbaud, A; Deibener-Kaminsky, J; Schmutz, J-L

2016-01-01

Dermatomyositis (DM) is an inflammatory disease associated with auto-antibodies in 50 to 70% of cases. A new antibody, anti MDA-5, has been described in association with a specific type of DM involving severe interstitial lung disease and minimal muscle disease. We report the first case of DM with MDA-5 antibodies and with interstitial lung disease and rapidly extensive digital necrosis. A 28-year-old male was hospitalized for asthenia, myalgia and subacute dyspnea. Examination demonstrated skin lesions with edema on every digit associated with purpuric and cyanotic lesions, as well as erythematous papules on the helix and the elbows, and Gottron's papules. Systemic corticosteroid therapy was initiated. The immunoprecipitation results indicated the presence of anti-MDA-5 antibodies. Despite corticosteroid therapy, the patient's respiratory status gradually deteriorated towards pulmonary fibrosis and rapidly extensive necrosis appeared on all fingers and toes. Theses effects were resistant to cyclophosphamide and immunoglobulin but were stabilized by cyclosporine. Anti-MDA-5 antibodies are specific to DM and constitute a risk factor for severe interstitial lung disease (70% of cases) with a higher risk of mortality (40%). The cutaneous presentation of this DM is specific with palmar papules and mucocutaneous ulceration. Rapidly extensive digital necrosis has not been previously reported. No treatment has demonstrated superiority. We report the first case of DM with anti-MDA-5 antibodies involving interstitial lung disease and massive digital necrosis. Because of the pulmonary risk, in the presence of clinical lesions containing anti-MDA-5 DM, screening for these antibodies should be carried out. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Necrosis in fingers and toes following local anaesthesia with adrenaline--an urban legend?].

PubMed

Finsen, Vilhjalmur

2013-09-17

It is often maintained that a local anaesthetic (usually lidocaine) with adrenaline must not be used in fingers and toes because it may cause necrosis due to vascular spasm in end arteries. This review article is an attempt to find evidence to support this warning. Relevant literature was found by means of searches in PubMed limited downwards to 1946 and in EMBASE from 1980 to 2012, and in reference lists. Five review articles on finger necrosis following local anaesthesia concluded that lidocaine with adrenaline does not entail a risk of ischaemic injury. One article found 48 reported cases of finger necrosis in the period 1880 to 2000. Most were from the first half of the 1900s, and none involved lidocaine. Gangrene of part of the finger tip has subsequently been described in one patient with Raynaud's syndrome. No cases of necrosis have been described in a large number of reported accidents in which EpiPen injections contained the same quantity of adrenaline as is found in 60 ml lidocaine with adrenaline. Over a quarter of a million reports have been made of operations on feet, hands, fingers and toes anaesthetised with lidocaine with adrenaline without resulting necrosis. There are no grounds for the warning against using lidocaine with adrenaline in fingers and toes. This anaesthetic offers considerable practical advantages. Care should be taken with infected fingers or fingers with poor circulation.

Acute esophageal necrosis caused by alcohol abuse

PubMed Central

Endo, Tetsu; Sakamoto, Juichi; Sato, Ken; Takimoto, Miyako; Shimaya, Koji; Mikami, Tatsuya; Munakata, Akihiro; Shimoyama, Tadashi; Fukuda, Shinsaku

2005-01-01

Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture. PMID:16222758

Medication-induced acute esophageal necrosis: a case report.

PubMed

Pautola, Lauri; Hakala, Tapio

2016-09-29

Acute esophageal necrosis or Gurvits syndrome is a rare clinical condition characterized by necrotic esophageal mucosa with an abrupt end at the gastroesophageal junction. Its etiology is multifactorial, but mainly related to low-flow states. We describe a case in which a patient accidentally took the wrong medication, with clozapine and olanzapine most probably being the cause of his subsequent acute esophageal necrosis. This situation is, to the best of our knowledge, unprecedented in the medical literature. A 65-year-old Finnish male patient with schizoaffective disorder accidentally took another patient's medication, including clozapine 300 mg, olanzapine 30 mg, teofyllamine 200 mg, warfarin 5 mg, and potassium chloride 1 g. He arrived at our hospital for a routine examination 6 h after the incident. At hospital he started to vomit brownish liquid and had tachycardia and fever. Gastroparesis was found. An endoscopy revealed necrotic esophageal mucosa that was typical for Gurvits syndrome. A computed tomography scan showed an edematous esophagus and raised suspicion of a proximal jejunal obstruction. A laparotomy was performed but only healthy paralytic bowel was found. Our patient healed uneventfully within a week. There are analogous case reports describing ischemic colitis associated with the use of clozapine and olanzapine, but none describing the same for the other medications our patient took. We believe that in this case clozapine and olanzapine caused acute esophageal necrosis and this possibility should be taken into account when treating patients with acute ischemic enteropathy.

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.

Sarcoidosis with prominent necrosis on histopathology.

PubMed

Rosenstein, Rachel; Orme, Charisse; Kim, Randie H; Meehan, Shane A; Femia, Alisa

2016-12-15

Sarcoidosis is a multiorgan inflammatory diseasewith variable clinical presentations and the commonhistopathologic finding of noncaseating granulomas.The etiology of the disease is not known, butevidence suggests both environmental and geneticcontributions to the pathogenesis. Depending onthe severity of cutaneous disease and extent ofextracutaneous involvement, therapies range fromtopical and intralesional glucocorticoids to systemicimmunomodulatory and immunosuppressiveagents. We present the case of a patient withcutaneous sarcoidosis with prominent necrosis onhistopathologic examination in the setting of severepulmonary sarcoidosis.

Non-vascularized iliac bone grafting for scaphoid nonunion with avascular necrosis.

PubMed

Kim, Jihyeung; Park, Jin Woo; Chung, Jeehyeok; Jeong Bae, Kee; Gong, Hyun Sik; Baek, Goo Hyun

2018-01-01

We present the surgical outcomes of non-vascularized bone grafting taken from the iliac crest in 24 patients with scaphoid nonunion and avascular necrosis. The Fisk-Fernandez technique was used in 11 patients, and cancellous bone grafting was used in 13 patients. Bony union was achieved in 22 of the 24 patients. Non-vascularized iliac bone grafting can be used for the surgical management of scaphoid nonunion with avascular necrosis. Although revascularization of the proximal fragment after surgery was not evaluated, bony union was confirmed in nearly all patients. IV.

Monocyte Tumor Necrosis Factor-α–Converting Enzyme Catalytic Activity and Substrate Shedding in Sepsis and Noninfectious Systemic Inflammation*

PubMed Central

O’Callaghan, David J. P.; O’Dea, Kieran P.; Scott, Alasdair J.; Takata, Masao

2015-01-01

Objectives: To determine the effect of severe sepsis on monocyte tumor necrosis factor-α–converting enzyme baseline and inducible activity profiles. Design: Observational clinical study. Setting: Mixed surgical/medical teaching hospital ICU. Patients: Sixteen patients with severe sepsis, 15 healthy volunteers, and eight critically ill patients with noninfectious systemic inflammatory response syndrome. Interventions: None. Measurements and Main Results: Monocyte expression of human leukocyte antigen-D-related peptide, sol-tumor necrosis factor production, tumor necrosis factor-α–converting enzyme expression and catalytic activity, tumor necrosis factor receptor 1 and 2 expression, and shedding at 48-hour intervals from day 0 to day 4, as well as p38-mitogen activated protein kinase expression. Compared with healthy volunteers, both sepsis and systemic inflammatory response syndrome patients’ monocytes expressed reduced levels of human leukocyte antigen-D-related peptide and released less sol-tumor necrosis factor on in vitro lipopolysaccharide stimulation, consistent with the term monocyte deactivation. However, patients with sepsis had substantially elevated levels of basal tumor necrosis factor-α–converting enzyme activity that were refractory to lipopolysaccharide stimulation and this was accompanied by similar changes in p38-mitogen activated protein kinase signaling. In patients with systemic inflammatory response syndrome, monocyte basal tumor necrosis factor-α–converting enzyme, and its induction by lipopolysaccharide, appeared similar to healthy controls. Changes in basal tumor necrosis factor-α–converting enzyme activity at day 0 for sepsis patients correlated with Acute Physiology and Chronic Health Evaluation II score and the attenuated tumor necrosis factor-α–converting enzyme response to lipopolysaccharide was associated with increased mortality. Similar changes in monocyte tumor necrosis factor-α–converting enzyme activity could

Radiotherapy and nipple-areolar complex necrosis after nipple-sparing mastectomy: a systematic review and meta-analysis.

PubMed

Zheng, Yajuan; Zhong, Miaochun; Ni, Chao; Yuan, Hongjun; Zhang, Jingxia

2017-03-01

To perform a meta-analysis to determine the effect of radiotherapy (RT) on nipple-areolar complex (NAC) and skin flap necrosis, and local recurrence in women who undergo nipple-sparing mastectomy (NSM) and immediate breast reconstruction. Medline, PubMed, Cochrane, and Google Scholar databases were searched until October 16, 2015. Randomized-controlled-trials, prospective, retrospective, and cohort studies were included. The primary outcome was the NAC necrosis rate, and the secondary outcomes were the skin flap necrosis and local recurrence rates. Of 186 studies identified, 2 prospective and 5 retrospective studies including a total of 3692 patients were included in the meta-analysis. Five, 3, and 2 studies reported data of NAC necrosis (3461 breasts), skin flap necrosis (2490 breasts), and local recurrence (988 breasts), respectively. Pooled results showed no difference in the odds of NAC necrosis [odds ratio (OR) = 1.250, 95% confidence interval (CI) 0.481-3.247, P = 0.647], or local recurrence (OR = 0.564, 95% CI 0.056-5.710, P = 0.627) between patients who received and did not receive RT. Patients treated with RT had a higher likelihood of skin flap necrosis (OR = 2.534, 95% CI 1.720-3.735, P < 0.001). Significant heterogeneity, however, was noted in the analysis of NAC and local recurrence. Because of the limitations of the small number of studies and heterogeneity in the analysis, this study does not allow drawing any definitive conclusions and highlights the need of well-controlled trials to determine the effect of RT in patients undergoing NSM.

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. 2016 BMJ Publishing Group Ltd.

Improving the Efficiency and Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury

DTIC Science & Technology

2013-10-01

2   INTRODUCTION: The magnitude of acute post- traumatic hemorrhagic necrosis (PHN) is an early prognostic indicator of long-term...Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury PRINCIPAL INVESTIGATOR: J. Marc Simard...Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury 5b. GRANT NUMBER W81XWH-10-1-0898 5c. PROGRAM ELEMENT NUMBER 6

Necrosis in human neuronal cells exposed to paraquat.

PubMed

Hirayama, Naho; Aki, Toshihiko; Funakoshi, Takeshi; Noritake, Kanako; Unuma, Kana; Uemura, Koichi

2018-01-01

Paraquat (PQ) is an herbicide that was once used worldwide, but is now prohibited in many nations due to its high toxicity to humans. However, there are still rare cases of the fetal intoxication of PQ, which was purchased prior to the prohibition in Japan. In this study, several cell death pathways, the mitochondrial stress response, and autophagy were examined in SH-SY5Y cells exposed to PQ. The results reveal the decrease of a mitochondrial stress sensitive-BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) protein, the suppression of autophagic flux, and the lack of apoptosis as well as other regulated forms of necrosis, such as necroptosis and ferroptosis. Taken together, our preliminary survey of cellular responses against PQ shows that, although responses of mitochondria and autophagy are observed, subsequent cell death is necrosis. Mechanism of PQ-induced SH-SY5Y cell death should be complicated and cannot be explained thoroughly by already-known mechanisms.

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.

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

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.

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. © 2014 International Society of Neuropathology.

[Avascular necrosis of the femoral head].

PubMed

Porubský, Peter; Trč, Tomáš; Havlas, Vojtěch; Smetana, Pavel

Avascular necrosis of the femoral head in adults is not common, but not too rare diseases. In orthopedic practice, it is one of the diseases that are causing implantation of hip replacement at a relatively early age. In the early detection and initiation of therapy can delay the implantation of prosthesis for several years, which is certainly more convenient for the patient and beneficial. This article is intended to acquaint the reader with the basic diagnostic procedures and therapy.

Targeted Gene Silencing of Tumor Necrosis Factor Attenuates the Negative Inotropic Effects of Lipopolysaccharide in Isolated Contracting Cardiac Myocytes

PubMed Central

Ramabadran, R. S.; Chancey, Amanda; Vallejo, Jesus G.; Barger, Philip M.; Sivasubramanian, Natarajan; Mann, Douglas L.

2008-01-01

Bacterial endotoxin (lipopolysaccharide) depresses cardiovascular function; however, the mediators and signaling pathways that are responsible for the negative inotropic effects of lipopolysaccharide are not fully known. We used RNA interference to determine the relative role of tumor necrosis factor with respect to mediating the negative inotropic effects of lipopolysaccharide in isolated cardiac myocytes. Cardiac myocyte cultures were treated with lipopolysaccharide in the presence or absence of small interfering RNAs (siRNA) for tumor necrosis factor. We examined the effects of tumor necrosis factor siRNA on lipopolysaccharide-induced tumor necrosis factor messenger RNA (mRNA) and protein biosynthesis, as well as the negative inotropic effects of lipopolysaccharide in isolated contracting cardiac myocytes. Treatment of adult cardiac myocyte cultures with tumor necrosis factor siRNA significantly attenuated lipopolysaccharide-induced tumor necrosis factor mRNA and protein biosynthesis, whereas transfection with a double-stranded RNA that does not target mammalian mRNA had no effect. Pretreatment with tumor necrosis factor siRNA significantly attenuated, but did not abrogate, the lipopolysaccharide-induced decrease in sarcomere shortening in isolated contracting cardiac myocytes. In contrast, tumor necrosis factor siRNA had a comparatively smaller effect on improving sarcomere shortening once the negative inotropic effects of lipopolysaccharide were fully established. These results suggest that tumor necrosis factor plays an important upstream role in lipopolysaccharide-induced negative inotropic effects in isolated contracting cardiac myocytes and that other molecular mechanisms are responsible for the decrease in sarcomere shortening after sustained lipopolysaccharide signaling. PMID:18427645

Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder.

PubMed

Hodgson, Anjelica; Xu, Bin; Satkunasivam, Raj; Downes, Michelle R

2018-02-01

Inflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of the bladder to determine their association with pathological parameters and their prognostic effect on relapse-free and disease-specific survival. A retrospective cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was evaluated for invasive front and central inflammation using the Klintrup-Makinen assessment method. Necrosis was scored using a four-point scale. The relationship of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour size, margin status and vascular space invasion and the impact on relapse-free and disease-specific survival were calculated using appropriate statistical tests. On multivariate analysis, invasive front inflammation (p=0.003) and necrosis (p=0.000) were independent predictors of relapse-free survival. Both invasive front inflammation (p=0.009) and necrosis (p=0.002) again were independent predictors of disease-specific survival. For pathological features, low invasive front inflammation was associated with lymphovascular space invasion (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ (p=0.042). Necrosis was statistically associated with tumours >3 cm in size (p=0.013) and carcinoma in situ (p<0.001). Necrosis and invasive front inflammation are additional histological variables with independent prognostic relevance in high-grade urothelial carcinoma of the bladder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

PubMed

Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

2017-07-01

To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

A study on the evaluation method and recent clinical efficacy of bevacizumab on the treatment of radiation cerebral necrosis.

PubMed

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

2016-04-12

In order to investigate the efficacy of bevacizumab on the treatment of radiation cerebral necrosis, patients who were diagnosed with radiation cerebral necrosis by imaging after stereotactic radiotherapy were collected. Bevacizumab was applied at a dose of 5 mg/kg once every three weeks at least three times. The changes in cerebral necrosis symptoms before and after treatment, the cerebral edema volume, the cerebral necrosis volume, and the changes in magnetic resonance imaging (MRI) strengthening phase signals of cerebral necrosis were used as the first observation point. The side effects of bevacizumab were used as the second observation point. Total of 14 radiation cerebral necrosis patients were treated with bevacizumab between June 2011 and February 2013 were collected. There were 12 symptomatic patients, of whom 10 patients (83.3%) had reduced symptoms. The edema index grades of nine patients (64.29%) improved. The cerebral necrosis volumes of 13 patients (92.86%) decreased. The T1 phase signal strengths of the intracranial enhanced MRIs of 12 patients (85.71%) significantly decreased. The clinical side effects of bevacizumab were mild. In conclusion, Preliminary results showed that treatment of radiation cerebral necrosis using bevacizumab was safe and effective. This treatment measure is worthy of further study.

A study on the evaluation method and recent clinical efficacy of bevacizumab on the treatment of radiation cerebral necrosis

PubMed Central

Zhuang, Hongqing; Yuan, Xiangkun; Zheng, Yi; Li, Xubin; Chang, Joe Y.; Wang, Junjie; Wang, Xiaoguang; Yuan, Zhiyong; Wang, Ping

2016-01-01

In order to investigate the efficacy of bevacizumab on the treatment of radiation cerebral necrosis, patients who were diagnosed with radiation cerebral necrosis by imaging after stereotactic radiotherapy were collected. Bevacizumab was applied at a dose of 5 mg/kg once every three weeks at least three times. The changes in cerebral necrosis symptoms before and after treatment, the cerebral edema volume, the cerebral necrosis volume, and the changes in magnetic resonance imaging (MRI) strengthening phase signals of cerebral necrosis were used as the first observation point. The side effects of bevacizumab were used as the second observation point. Total of 14 radiation cerebral necrosis patients were treated with bevacizumab between June 2011 and February 2013 were collected. There were 12 symptomatic patients, of whom 10 patients (83.3%) had reduced symptoms. The edema index grades of nine patients (64.29%) improved. The cerebral necrosis volumes of 13 patients (92.86%) decreased. The T1 phase signal strengths of the intracranial enhanced MRIs of 12 patients (85.71%) significantly decreased. The clinical side effects of bevacizumab were mild. In conclusion, Preliminary results showed that treatment of radiation cerebral necrosis using bevacizumab was safe and effective. This treatment measure is worthy of further study. PMID:27067388

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 unventilatedmore » 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.« less

Superimposition of maximal stress and necrosis areas at the top of the femoral head in hip aseptic osteonecrosis.

PubMed

Escudier, J-C; Ollivier, M; Donnez, M; Parratte, S; Lafforgue, P; Argenson, J-N

2018-05-01

Recent reports described possible mechanical factors in the development and aggravation of osteonecrosis of the femoral head (OFH), but these have yet to be confirmed on dedicated mechanical study. We therefore developed a 3D finite element model based on in-vivo data from patients with incipient OFH, with a view to determining whether the necrosis area was superimposed on the maximal stress area on the femoral head. The location of the necrosis area is determined by stress on the femoral head. All patients from the rheumatology department with early stage OFH in our center were investigated. Analysis of CT scans showed stress distribution on the head by 3D finite elements models, enabling determination of necrosis volume within the maximal stress area and of the percentage intersection of necrosis within the stress area (%I n/s: necrosis volume in stress area divided by total stress area volume and multiplied by 100) and of stress within the necrosis area (%I s/n: stress volume in necrosis area divided by total necrosis area volume and multiplied by 100). Nineteen of the 161 patients assessed retrospectively for the period between 2006 and 2015 had incipient unilateral OFH, 10 of whom (4 right, 6 left) had CT scans of sufficient quality for inclusion. Mean age was 52 years (range, 37-81 years). Mean maximal stress was 1.63MPa, mean maximal exported stress volume was 2,236.9 mm 3 and mean necrosis volume 6,291.1 mm 3 . Mean %I n/s was 83% and mean %I s/n 35%, with no significant differences according to gender, age, side or stress volume. There was a strong inverse correlation between necrosis volume and %I s/n (R 2 =-0.92) and a strong direct correlation between exported stress volume and %I s/n (R 2 =0.55). %I s/n was greater in small necrosis (<7,000mm 3 ). OFH seems to develop within the maximal stress area on the femoral head. The present results need confirmation by larger-scale studies. We consider it essential to take account of these mechanical parameters

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

CHOP mediates XBP1S-induced renal mesangial cell necrosis following high glucose treatment.

PubMed

Shao, Decui; Ni, Jun; Shen, Yang; Liu, Jia; Zhou, Li; Xue, Hong; Huang, Yu; Zhang, Wei; Lu, Limin

2015-07-05

High glucose (HG)-induced apoptosis in mesangial cells (MCs) is a critical determinant during the pathogenesis of diabetic nephropathy. The signaling cascade inducing MCs apoptosis by HG involves overproduction of reactive oxygen species. Our previous studies have demonstrated that HG-induced oxidative stress is mediated by suppression of spliced/active X-box binding protein 1 (XBP1S), suggesting the importance of XBP1S in HG-induced MCs apoptosis. CHOP, an endoplasmic reticulum stress-associated proapoptotic signal, is involved in downstream of XBP1S. In the present study, we explored the effect of XBP1S in modulating HG-induced apoptosis in renal MCs and then identified the role of CHOP in these processes. Apoptosis and necrosis were quantified by flow cytometry; protein levels of XBP1S, caspase3, Bax, Bcl2, BNIP3, and CHOP were analyzed by Western blotting. The cellular localization of XBP1S was determined by immunofluorescence histochemistry. The binding of XBP1 to CHOP promoter was determined by chromatin immunoprecipitation assays. In addition, adenoviruses harboring XBP1S gene (Ad-XBP1S) were used to overexpress XBP1S, whereas the knockdown of CHOP was achieved by small interference RNA. HG suppressed nuclear distribution of XBP1S and induced apoptosis and necrosis in MCs. Ad-XBP1S infection enhanced the nuclear translocation of XBP1S and reduced MCs apoptosis and necrosis. XBP1S bound to the promoter region of CHOP and upregulated CHOP expression. Conversely, CHOP expression was reduced upon HG exposure and knockdown of CHOP increased necrosis but not apoptosis in MCs. These results suggest that XBP1S protected MCs from HG-induced apoptosis and necrosis, and CHOP participates in XBP1S-regulated necrosis but not apoptosis. Copyright © 2015. Published by Elsevier B.V.

Excretion and toxicity evaluation of 131I-Sennoside A as a necrosis-avid agent.

PubMed

Yin, Zhiqi; Sun, Lidan; Jin, Qiaomei; Song, Shaoli; Feng, Yuanbo; Liao, Hong; Ni, Yicheng; Zhang, Jian; Liu, Wei

2017-11-01

1. Sennoside A (SA) is a newly identified necrosis-avid agent that shows capability for imaging diagnosis and tumor necrosis targeted radiotherapy. As a water-soluble compound, 131 I-Sennoside A ( 131 I-SA) might be excreted predominately through the kidneys with the possibility of nephrotoxicity. 2. To further verify excretion pathway and examine nephrotoxicity of 131 I-SA, excretion and nephrotoxicity were appraised. The pharmacokinetics, hepatotoxicity and hematotoxicity of 131 I-SA were also evaluated to accelerate its possible clinical translation. All these studies were conducted in mice with ethanol-induced muscular necrosis following a single intravenous administration of 131I-SA at 18.5 MBq/kg or 370 MBq/kg. 3. Excretion data revealed that 131 I-SA was predominately (73.5% of the injected dose (% ID)) excreted via the kidneys with 69.5% ID detected in urine within 72 h post injection. Biodistribution study indicated that 131 I-SA exhibited initial high distribution in the kidneys but subsequently a fast renal clearance, which was further confirmed by the results of autoradiography and single-photon emission computed tomography-computed tomography (SPECT-CT) imaging. The maximum necrotic to normal muscle ratio reached to 7.9-fold at 48 h post injection, which further verified the necrosis avidity of 131 I-SA. Pharmacokinetic parameters showed that 131 I-SA had fast blood clearance with an elimination half-life of 6.7 h. Various functional indexes were no significant difference (p > 0.05) between before administration and 1 d, 8 d, 16 d after administration. Histopathology showed no signs of tissue damage. 4. These data suggest 131 I-SA is a safe and promising necrosis-avid agent applicable in imaging diagnosis and tumor necrosis targeted radiotherapy.

Necrosis of the tail of pancreas following proximal splenic artery embolization

PubMed Central

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

Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited.

PubMed

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

2011-08-01

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 Ca(2+) accumulation (EICA), and mitochondrial Ca(2+) 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.

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

Risk factors leading to mucoperiosteal flap necrosis after primary palatoplasty in patents with cleft palate.

PubMed

Rossell-Perry, Percy; Figallo-Hudtwalcker, Olga; Vargas-Chanduvi, Roberto; Calderon-Ayvar, Yvette; Romero-Narvaez, Carolina

2017-10-01

Few studies have been published reporting risk factors for flap necrosis after primary palatoplasty in patients with cleft palate. This complication is rare, and the event is a disaster for both the patient and the surgeon. This study was performed to explore the associations between different risk factors and the development of flap necrosis after primary palatoplasty in patients with cleft palate. This is a case-control study. A 20 years retrospective analysis (1994-2015) of patients with nonsyndromic cleft palate was identified from medical records and screening day registries). Demographical and risk factor data were collected using a patient´s report, including information about age at surgery, gender, cleft palate type, and degree of severity. Odds ratios and 95% confident intervals were derived from logistic regression analysis. All cases with diagnoses of flap necrosis after primary palatoplasty were included in the study (48 patients) and 156 controls were considered. In multivariate analysis, female sex, age (older than 15 years), cleft type (bilateral and incomplete), and severe cleft palate index were associated with significantly increased risk for flap necrosis. The findings suggest that female sex, older age, cleft type (bilateral and incomplete), and severe cleft palatal index may be associated with the development of flap necrosis after primary palatoplasty in patients with cleft palate.

Intestinal volvulus with coagulative hepatic necrosis in a chicken.

PubMed

Haridy, Mohie; Goryo, Masanobu; Sasaki, Jun; Okada, Kosuke

2010-04-01

A 7-week-old SPF chicken inoculated at 4 weeks of age with chicken anemia virus was puffed up depressed and had ruffled feathers and a good body condition. Intestinal volvulus involving the jejunum and part of the duodenum forming two loops with one knob was observed. Microscopically, venous infarction of the obstructed loops, periportal and sublobular multifocal coagulative hepatic necrosis and granulomatous inflammation of the cecal tonsils were observed. Gram staining revealed no bacteria in hepatic tissue; however, gram-positive bacilli were detected in the necrotic debris in the intestinal lumen. Immunosuppression might have predisposed the chicken to intestinal and cecal tonsil infection that then progressed to volvulus. Loss of the mucosal barrier in infarction might allow bacterial toxins and vasoactive factors to escape into the systemic circulation (toxemia) and be responsible for the hepatic necrosis.

Lipolysis of Visceral Adipocyte Triglyceride by Pancreatic Lipases Converts Mild Acute Pancreatitis to Severe Pancreatitis Independent of Necrosis and Inflammation

PubMed Central

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

2016-01-01

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

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

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.

Recombinant infectious hematopoietic necrosis virus expressing infectious pancreatic necrosis virus VP2 protein induces immunity against both pathogens.

PubMed

Guo, Mengting; Shi, Wen; Wang, Yanxue; Wang, Yuting; Chen, Yaping; Li, Dechuan; Ren, Xuanyu; Hua, Xiaojing; Tang, Lijie; Li, Yijing; Liu, Min

2018-04-21

Infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are typical pathogens of rainbow trout. Their co-infection is also common, which causes great economic loss in juvenile salmon species. Although vaccines against IHNV and IPNV have been commercialized in many countries, the prevalence of IHNV and IPNV is still widespread in modern aquaculture. In the present study, two IHNV recombinant viruses displaying IPNV VP2 protein (rIHNV-IPNV VP2 and rIHNV-IPNV VP2COE) were generated using the RNA polymerase Ⅱ system to explore the immunogenicity of IHNV and IPNV. The recombinant IHNV viruses were stable, which was confirmed by sequencing, indirect immunofluorescence assay, western blotting, transmission electron microscopy and viral growth curve assay. IHNV and IPNV challenge showed that the recombinant viruses had high protection rates against IHNV and IPNV with approximately 65% relative percent survival rates. Rainbow trout (mean weight 20 g) vaccinated with these two recombinant viruses showed a high level of antibodies against IHNV and IPNV infection. Taken together, our findings demonstrate that rIHNV-IPNV VP2 and rIHNV-IPNV VP2COE might be promising vaccine candidates against IHNV and IPNV. Copyright © 2018. Published by Elsevier Ltd.

Striatal necrosis in type 1 glutaric aciduria: Different stages in two siblings.

PubMed

Sen, Anitha; Pillay, Rajesh Subramonia

2011-07-01

Two siblings born of a consanguineous marriage with history of neurologic deterioration were imaged. Imaging features are classical of glutaric aciduria type 1 (GA-1), acute (striatal necrosis) stage in younger sibling, and chronic stage in older sibling. GA-1 is an autosomal recessive disease with typical imaging features. Greater awareness about this condition among clinicians and radiologists is essential for early diagnosis and prevention of its catastrophic consequences. Striatal necrosis with stroke-like signal intensity on imaging correlates with clinical stage of patients.

Striatal necrosis in type 1 glutaric aciduria: Different stages in two siblings

PubMed Central

Sen, Anitha; Pillay, Rajesh Subramonia

2011-01-01

Two siblings born of a consanguineous marriage with history of neurologic deterioration were imaged. Imaging features are classical of glutaric aciduria type 1 (GA-1), acute (striatal necrosis) stage in younger sibling, and chronic stage in older sibling. GA-1 is an autosomal recessive disease with typical imaging features. Greater awareness about this condition among clinicians and radiologists is essential for early diagnosis and prevention of its catastrophic consequences. Striatal necrosis with stroke-like signal intensity on imaging correlates with clinical stage of patients. PMID:22408669

Avascular necrosis of the femoral head post heart-transplantation and steroid dosage.

PubMed

Foley-Nolan, D; Daly, C; Barry, C; Woods, A; Neligan, M; Coughlan, R J

1992-12-01

Avascular necrosis (avn) post heart-transplantation has been considered to be due to the high doses of steroids used to immunosuppress these patients in attempting to prevent transplant rejection. This study shows that avascular necrosis occurs even when low dose steroids regimes are used and demonstrates no significant correlation between steroid dosage and the development of avn. Patients with symptomatic avn benefit from early diagnosis and management of their condition in that the need for total joint arthroplasty can be prevented in many cases.

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. © The Author(s) 2015.

Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

PubMed

Sato, Miho; Mori, Masaaki; Nishimaki, Shigeru; An, Hiromi; Naruto, Takuya; Sugai, Toshiyuki; Shima, Yoshio; Seki, Kazuo; Yokota, Shumpei

2010-04-01

It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

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

Model-Based Radiation Dose Correction for Yttrium-90 Microsphere Treatment of Liver Tumors With Central Necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ching-Sheng; Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Lin, Ko-Han

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 wasmore » 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.« less

Favorable Prognosis in Patients With High-Grade Glioma With Radiation Necrosis: The University of Colorado Reoperation Series

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusthoven, Kyle E.; Olsen, Christine; Franklin, Wilbur

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 andmore » 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.« less

DNA damage in lead-exposed hepatocytes: coexistence of apoptosis and necrosis?

PubMed

Narayana, Kilarkaje; Raghupathy, Raj

2012-04-01

The aim of the present study was to investigate the coexistence of oxidative DNA damage and apoptosis- and necrosis-related DNA damage, and to correlate with ultrastructural changes in hepatocyte nuclei in the lead-nitrate-exposed liver. Adult male Wistar rats were exposed to 0, 0.5, and 1% lead nitrate for 60 days, and the livers were sampled the next day. Ultrastructurally, hepatocyte nuclei showed no apoptosis-related morphological changes, but showed necrotic changes. Competitive enzyme-linked immunosorbent assay showed no change in 8-oxo-dG activity (P > 0.05), but immunohistochemistry showed its localization in hepatocytes, Kupffer cells, endothelium, and bile ductule epithelium. TUNEL-labeled DNA breaks presenting 3'-OH ends increased in hepatocytes in all functional zones of the portal acini and bile ductule epithelium (zones I>III>II). In situ oligo ligation revealed the existence of DNA breaks bearing duplex 3' overhangs and 5' P-blunt ends in hepatocytes of all functional zones and bile ductule epithelium. In conclusion, both apoptosis- and necrosis-related DNA damage coexist without significant oxidative DNA damage. Hepatocytes display changes related to necrosis, but not those related to apoptosis.

First evidence of infectious hematopoietic necrosis virus (IHNV) in the Netherlands.

PubMed

Haenen, O L M; Schuetze, H; Cieslak, M; Oldenburg, S; Spierenburg, M A H; Roozenburg-Hengst, I; Voorbergen-Laarman, M; Engelsma, M Y; Olesen, N J

2016-08-01

In spring 2008, infectious hematopoietic necrosis virus (IHNV) was detected for the first time in the Netherlands. The virus was isolated from rainbow trout, Oncorhynchus mykiss (Walbaum), from a put-and-take fishery with angling ponds. IHNV is the causative agent of a serious fish disease, infectious hematopoietic necrosis (IHN). From 2008 to 2011, we diagnosed eight IHNV infections in rainbow trout originating from six put-and-take fisheries (symptomatic and asymptomatic fish), and four IHNV infections from three rainbow trout farms (of which two were co-infected by infectious pancreatic necrosis virus, IPNV), at water temperatures between 5 and 15 °C. At least one farm delivered trout to four of these eight IHNV-positive farms. Mortalities related to IHNV were mostly <40%, but increased to nearly 100% in case of IHNV and IPNV co-infection. Subsequent phylogenetic analysis revealed that these 12 isolates clustered into two different monophyletic groups within the European IHNV genogroup E. One of these two groups indicates a virus-introduction event by a German trout import, whereas the second group indicates that IHNV was already (several years) in the Netherlands before its discovery in 2008. © 2016 John Wiley & Sons Ltd.

Porphyrin-laser photodynamic induction of focal brain necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stroop, W.G.; Battles, E.J.; Townsend, J.J.

A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scalp with 632 nm argon-dye laser light. Animals were studied at one, two and seven days after irradiation. Blood-brain barrier damage was detected by the intravenous injection of Evans blue, horseradish peroxidase and heterologous immunoglobulins. At one and two days after irradiation, the lesions were characterized by extravasation of immunoglobulin and Evans blue, and bymore » edema, ischemia and infiltration by monocytes. On the seventh day after irradiation, the lesion was smaller than it had been two days after irradiation, and had reactive changes at its edges and coagulative necrosis at its center. Extravasation of Evans blue and immunoglobulin was markedly reduced by the seventh day after irradiation, but uptake of horseradish peroxidase by macrophages located at the periphery of the lesion was evident.« less

Necrosis of the femoral head after kidney transplantation.

PubMed

Lausten, G S; Lemser, T; Jensen, P K; Egfjord, M

1998-12-01

We reviewed the medical records of 750 patients (445 men, 305 women), who had received a kidney transplant during the period 1968-1995, for any sign of necrosis of the femoral head. For post-operative immunosuppression, 374 patients had received high-dose corticosteroids (average 12.5 g during the first year post-operatively), while 376 patients had received low-dose corticosteroids (average 6.5 g during the first year post-operatively) and cyclosporin A. Survival curves according to Kaplan and Meier (J Am Stat Ass 1958: 53: 457-481) were constructed. In the high-dose steroid group, 42/374 patients (11.2%) developed femoral head necrosis, at an average of 26.2 months post-transplantation. In the low-dose steroid group, only 19/376 (5.1%) patients developed this complication, at an average of 20.5 months post-transplantation. This difference in numbers of femoral head necroses was highly significant (p < 0.005). We conclude that steroid doses should be minimized whenever feasible in post-transplant immunosuppression therapy.

Risk Factor Analysis for Mastectomy Skin Flap Necrosis: Implications for Intraoperative Vascular Analysis.

PubMed

Reintgen, Christian; Leavitt, Adam; Pace, Elizabeth; Molas-Pierson, Justine; Mast, Bruce A

2016-06-01

Skin flap necrosis after mastectomy can be a devastating complication significantly affecting patient outcomes. Routine vascular analysis (fluorescein or laser angiography) of mastectomy skin flaps in all patients has been advocated but is of questionable cost-effectiveness. The purpose of this study was to identify the incidence and causative risk factors for mastectomy skin flap necrosis and thereby calculate the fiscal reality of intraoperative vascular screening. This is an institutional review board-approved retrospective study of all patients from 2007 to 2013 who underwent mastectomy related to breast cancer. Skin flap necrosis was defined as major if it necessitated return to the operating room. Data analysis was done for determination of causative factors of necrosis, including age, body mass index, smoking, previous irradiation, coronary artery disease, chronic obstructive pulmonary disorder, hypertension, gastroesophageal reflux disease, hyperlipidemia, obstructive sleep apnea, asthma, diabetes, thyroid disease, history of lumpectomy, and breast reduction or augmentation. During this time, intraoperative vascular screening was not done. Five hundred eighty-one patients underwent 616 mastectomies with a total of 34 necrotic events (5.5%)-16 major and 18 minor. Analyses via Student t tests, univariate analyses, χ testing, and logistic regression showed that history of smoking was the only patient factor associated with postoperative necrosis (P = 0.008). More frequently represented in the necrosis group, but without statistical significance, are previous lumpectomy (P = 0.069) and immediate reconstruction (P = 0.078).For the entire study period, the actual cost to the hospital for major necrotic events was $7,123.10 or $445.19 for each of the 16 major necrotic events and $209.50 for all 34 necrotic events. Per-patient cost-effective screening would need to be less than $11.54 for all patients, $100.33 for highest risk patients (smokers), and $21.65 for

NEMO Inhibits Programmed Necrosis in an NFκB-Independent Manner by Restraining RIP1

PubMed Central

Legarda, Diana; Ting, Adrian T.

2012-01-01

TNF can trigger two opposing responses: cell survival and cell death. TNFR1 activates caspases that orchestrate apoptosis but some cell types switch to a necrotic death when treated with caspase inhibitors. Several genes that are required to orchestrate cell death by programmed necrosis have been identified, such as the kinase RIP1, but very little is known about the inhibitory signals that keep this necrotic cell death pathway in check. We demonstrate that T cells lacking the regulatory subunit of IKK, NFκB essential modifier (NEMO), are hypersensitive to programmed necrosis when stimulated with TNF in the presence of caspase inhibitors. Surprisingly, this pro-survival activity of NEMO is independent of NFκB-mediated gene transcription. Instead, NEMO inhibits necrosis by binding to ubiquitinated RIP1 to restrain RIP1 from engaging the necrotic death pathway. In the absence of NEMO, or if ubiquitination of RIP1 is blocked, necrosis ensues when caspases are blocked. These results indicate that recruitment of NEMO to ubiquitinated RIP1 is a key step in the TNFR1 signaling pathway that determines whether RIP1 triggers a necrotic death response. PMID:22848449

Rin4 causes hybrid necrosis and race-specific resistance in an interspecific lettuce hybrid.

PubMed

Jeuken, Marieke J W; Zhang, Ningwen W; McHale, Leah K; Pelgrom, Koen; den Boer, Erik; Lindhout, Pim; Michelmore, Richard W; Visser, Richard G F; Niks, Rients E

2009-10-01

Some inter- and intraspecific crosses may result in reduced viability or sterility in the offspring, often due to genetic incompatibilities resulting from interactions between two or more loci. Hybrid necrosis is a postzygotic genetic incompatibility that is phenotypically manifested as necrotic lesions on the plant. We observed hybrid necrosis in interspecific lettuce (Lactuca sativa and Lactuca saligna) hybrids that correlated with resistance to downy mildew. Segregation analysis revealed a specific allelic combination at two interacting loci to be responsible. The allelic interaction had two consequences: (1) a quantitative temperature-dependent autoimmunity reaction leading to necrotic lesions, lethality, and quantitative resistance to an otherwise virulent race of Bremia lactucae; and (2) a qualitative temperature-independent race-specific resistance to an avirulent race of B. lactucae. We demonstrated by transient expression and silencing experiments that one of the two interacting genes was Rin4. In Arabidopsis thaliana, RIN4 is known to interact with multiple R gene products, and their interactions result in hypersensitive resistance to Pseudomonas syringae. Site-directed mutation studies on the necrosis-eliciting allele of Rin4 in lettuce showed that three residues were critical for hybrid necrosis.

Avascular necrosis of the femoral head at 2 years after pertrochanteric fracture surgery: Case report.

PubMed

Deleanu, Bogdan; Prejbeanu, Radu; Vermesan, Dinu; Honcea, Lucian; Mioc, Mihail Lazar; Tsiridis, Eleftherios; Predescu, Vlad

2016-02-01

The avascular necrosis of the femoral head represents the death of bone tissue due to the lack of blood supply. The disease has a progressive evolution and left untreated leads to femoral head collapse and severe arthritis. We present a case of a pertrochanteric fracture which has been successfully operated with a dynamic interlocking trochanteric gamma nail on the right hip. At 2 years after surgery the patient developed an incipient avascular necrosis of the femoral head. Despite the good positioning of the implant, we considered that the source of the pain was an intolerance of the implant, and thus we removed it. After implant removal, the patient was kept under observation and conservative treatment, to prevent further damage to the right hip and allow the healing to occur. At 6 months after the gamma nail was removed the X-rays revealed advanced avascular necrosis of the femoral head and secondary osteoarthritis on the right hip. The patient underwent surgery with an uncemented total hip arthroplasty. There are a few discussions regarding the avascular necrosis of the femoral head. These discussions may include the predisposing risk factors, the treatment of choice and the postoperative complications. The avascular necrosis of the femoral head is a complication of pertrochanteric fractures that can not be foreseen or avoided. The optimal treatment in these cases is uncemented total hip arthroplasty.

Hip resurfacing arthroplasty in treatment of avascular necrosis of the femoral head.

PubMed

Pyda, Michał; Koczy, Bogdan; Widuchowski, Wojciech; Widuchowska, Małgorzata; Stołtny, Tomasz; Mielnik, Michał; Hermanson, Jacek

2015-01-25

Hip resurfacing is a conservative type of total hip arthroplasty but its use is controversial, especially in patients with osteonecrosis. The aim of this study was analysis of the clinical and radiographic outcomes of hip resurfacing in patients with osteonecrosis. Between 2007 and 2008, 30 hip resurfacing arthroplasties were performed due to osteoarthritis secondary to avascular necrosis of femoral head staged as Ficat III and IV. Patients were qualified to resurfacing arthroplasty when the extent of avascular necrosis using Kerboul's method was <200° and the angle between avascular necrosis and head-neck junction was >20°. All patients were evaluated clinically and radiologically before and 60 months after the operation. The mean Harris Hip Score (HHS) score increased from 47.8 to 94.25 (p<0.05). Physical activity level (University of California, Los Angeles activity score--UCLA activity score) improved from 3.7 to 7.55 (p<0.05). No implant migration was observed. Management of osteonecrosis of the hip with resurfacing arthroplasty seems to be effective in strictly-selected patients.

Hip Resurfacing Arthroplasty in Treatment of Avascular Necrosis of the Femoral Head

PubMed Central

Pyda, Michał; Koczy, Bogdan; Widuchowski, Wojciech; Widuchowska, Małgorzata; Stołtny, Tomasz; Mielnik, Michał; Hermanson, Jacek

2015-01-01

Background Hip resurfacing is a conservative type of total hip arthroplasty but its use is controversial, especially in patients with osteonecrosis. The aim of this study was analysis of the clinical and radiographic outcomes of hip resurfacing in patients with osteonecrosis. Material/Methods Between 2007 and 2008, 30 hip resurfacing arthroplasties were performed due to osteoarthritis secondary to avascular necrosis of femoral head staged as Ficat III and IV. Patients were qualified to resurfacing arthroplasty when the extent of avascular necrosis using Kerboul’s method was <200° and the angle between avascular necrosis and head-neck junction was >20°. All patients were evaluated clinically and radiologically before and 60 months after the operation. Results The mean Harris Hip Score (HHS) score increased from 47.8 to 94.25 (p<0.05). Physical activity level (University of California, Los Angeles activity score – UCLA activity score) improved from 3.7 to 7.55 (p<0.05). No implant migration was observed. Conclusions Management of osteonecrosis of the hip with resurfacing arthroplasty seems to be effective in strictly-selected patients. PMID:25618763

Matriderm for Management of Scalp Necrosis Following Surgical Treatment of Giant Parietal Encephalocele.

PubMed

Vilela, Marcelo D; Pedrosa, Hugo A S; Sampaio, Felipe D; Carneiro, Junia L

2018-02-01

Management of encephaloceles is challenging when massive brain herniation is present. In such instances, an expansile cranioplasty may be attempted so as to preserve some herniated brain tissue. Complications such as wound dehiscence, cerebrospinal fluid leak, and scalp necrosis are postoperative concerns. The treatment of scalp necrosis with dural and brain exposure is certainly a challenge due to the complexity of flap techniques in such a young age. Herein we describe the use of a novel technique for the management of a scalp necrosis and dehiscence in an infant. A patient with a giant parietal encephalocele and massive brain herniation underwent an expansile cranioplasty. A large scalp necrosis ensued as a complication and later progressed to a suture dehiscence despite a new surgical intervention, with resultant brain exposure. A scalp reconstruction was subsequently performed using an artificial dermal substitute, laid directly onto the brain, followed by a split-thickness skin graft. We observed a rapid engraftment, without any further complications, with an acceptable cosmetic result in the long-term follow-up. A simple technique, such as the use of an artificial dermal matrix with simultaneous split-thickness skin graft, may be an effective treatment for the repair of scalp defects, even when coverage of exposed brain tissue is necessary, when no other techniques are found to be suitable. Copyright © 2017 Elsevier Inc. All rights reserved.

Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma.

PubMed

Li, Yang-Chan; Chen, Fo-Ping; Zhou, Guan-Qun; Zhu, Jin-Han; Hu, Jiang; Kang, De-Hua; Wu, Chen-Fei; Lin, Li; Wang, Xiao-Ju; Ma, Jun; Sun, Ying

2017-10-01

To clarify the incidence of brainstem toxicity and perform a dose-volume analysis for the brainstem after long-term follow-up of a large cohort of nasopharyngeal carcinoma (NPC) patients who underwent intensity-modulated radiation therapy (IMRT). All patients with NPC treated with IMRT at Sun Yat-sen University Cancer Center between April 2009 and March 2012 were retrospectively reviewed. A total of 1544 patients with follow-up >12months and detailed treatment plan data were included. Radiotherapy was administered using the simultaneous integrated boost technique in 2.0-2.48Gy per fractions/28-33 fractions. Brainstem necrosis was defined as lesions with high signal intensity on T2-weighted images and low signal intensity on T1-weighted images, with or without enhancement after administration of contrast in follow-up MRI. After median follow-up of 79.7months (range, 12.2-85.6months), 2/1544 (0.13%) patients developed brainstem necrosis after intervals of 12.3 and 18.5months. Actuarial incidence of brainstem necrosis was 0.07%, 0.13%, 0.13% and 0.13% after 1, 2, 3 and 5years, respectively. Overall, 384 (24.9%), 153 (9.9%), 67 (4.3%), 39 (2.5%), 78 (5.1%), and 114 (7.4%) patients had excessive doses of D max ≥64Gy, D1cc>59Gy, D2cc>59Gy, aV50>5.9cc, aV55>2.7cc and aV60>0.9cc respectively, of whom only two developed brainstem necrosis. Brainstem necrosis is rare in NPC. The definitive criteria based on conventional radiotherapy cannot accurately predict the occurrence of brainstem necrosis after IMRT, thus more flexible definitive criteria with strict restrictions need to be defined. Copyright © 2017 Elsevier Ltd. All rights reserved.

Irregular echogenic foci representing coagulation necrosis: a useful but perhaps under-recognized EUS echo feature of malignant lymph node invasion.

PubMed

Bhutani, Manoop S; Saftoiu, Adrian; Chaya, Charles; Gupta, Parantap; Markowitz, Avi B; Willis, Maurice; Kessel, Ivan; Sharma, Gulshan; Zwischenberger, Joseph B

2009-06-01

Coagulation necrosis has been described in malignant lymph nodes. Our aim was to determine if coagulation necrosis in mediastinal lymph nodes imaged by EUS could be used as a useful echo feature for predicting malignant invasion. Patients with known or suspected lung cancer who had undergone mediastinal lymph node staging by EUS. Tertiary Care university hospital. An expert endosonographer blinded to the final diagnosis, reviewed the archived digital EUS images of lymph nodes prior to being sampled by FNA. LNs positive for malignancy by FNA were included. The benign group included lymph node images with either negative EUS-FNA or lymph nodes imaged by EUS but not subjected to EUS-FNA, with surgical correlation of their benign nature. 24 patients were included. 8 patients were found to have coagulation necrosis. 7/8 patients had positive result for malignancy by EUS-FNA. One patient determined to have coagulation necrosis had a non-malignant diagnosis indicating a false positive result. 16 patients had no coagulation necrosis. In 6 patients with no coagulation necrosis, the final diagnosis was malignant and in the remaining 10 cases, the final diagnosis was benign. For coagulation necrosis as an echo feature for malignant invasion, sensitivity was 54%, specificity was 91%, positive predictive value was 88%, negative predictive value was 63% and accuracy was 71%. Coagulation necrosis is a useful echo feature for mediastinal lymph node staging by EUS.

Breast necrosis secondary to vasopressor extravasation: management using indocyanine green angiography and omental flap closure.

PubMed

Hagopian, Thomas M; Ghareeb, Paul A; Arslanian, Brian H; Moosavi, Benjamin L; Carlson, Grant W

2015-01-01

Extravasation is a rare but serious complication of vasopressor administration. A 60-year-old female who underwent ascending and hemiarch repair of the aorta along with aortic valve replacement developed extensive right breast and chest wall necrosis after vasopressor extravasation from an internal jugular vein central line. The patient underwent a total mastectomy due to deep tissue necrosis detected by laser-assisted indocyanine green dye angiography, and eventually required omental flap reconstruction to obtain adequate sternal coverage. This case represents a previously unreported complication of internal jugular central line extravasation of vasopressors with resultant breast and chest wall necrosis, and highlights the utility of the omentum in chest wall reconstruction. © 2015 Wiley Periodicals, Inc.

Skin Necrosis After Implantation With the BAHA Attract: A Case Report and Review of the Literature.

PubMed

Chen, Stephanie Y; Mancuso, Dean; Lalwani, Anil K

2017-03-01

The bone-anchored hearing aid (BAHA) Attract is a transcutaneous bone conduction hearing aid that uses magnetic coupling to enable sound conduction. We report the first case of skin necrosis associated with the BAHA Attract and perform a literature review of soft tissue complications related to the device. A single patient who was found to develop skin necrosis 2 weeks after being fitted for the BAHA Attract speech processor. After the patient developed skin necrosis from the device, she was advised to immediately discontinue use of the Attract to allow complete wound healing, upon which the Attract was successfully converted to a percutaneous BAHA. We monitored for the development of skin complications from the BAHA Attract. The patient's immediate postoperative course was unremarkable and she was fitted with a speech processor of M5 magnet strength at 1 month postoperatively. After 1 week of use, she reported discomfort and was advised to downgrade to an M4 magnet; however, she continued to use the M5 and the following week was found to have developed skin necrosis around the device. Despite the infrequency of skin necrosis related to the BAHA Attract, it must be considered in counseling and managing candidates for the device.

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

2016-05-13

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. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

Avascular Necrosis of the Metacarpal Head: A Review of 4 Cases.

PubMed

Aldekhayel, Salah; Ghanad, Erfan; Mudgal, Chaitanya S

2018-04-03

To report on 4 cases of avascular necrosis of the metacarpal head. We retrospectively reviewed 4 patients who received a diagnosis of avascular necrosis of the metacarpal head and were treated from 2000 to 2016. All patients were males with involvement of the dominant hand. Three patients had a history of trauma and/or fractures in another finger and one had a history of fracture in the same finger. The diagnosis was confirmed on regular x-rays and magnetic resonance imaging. Nonsurgical management was offered to all patients (rest, placement of an orthosis, and nonsteroidal anti-inflammatory drugs) for 3 to 6 months. Two patients responded well to nonsurgical management and improved in their symptoms. One patient refused surgical intervention and continued to have persistent pain. The other patient was treated with curettage and bone graft and had total resolution of pain symptoms with full active range of motion. A high index of suspicion is required to diagnose and treat avascular necrosis of the metacarpal head correctly. Treatment options are numerous and require further studies to investigate their effectiveness in the treatment of this rare disease. Therapeutic V. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis

PubMed Central

Gaman, Laura; Robu, Georgiana Catalina; Radoi, Mugurel Petrinel; Stroica, Laura; Badea, Mihaela

2018-01-01

Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis. PMID:29686719

Plasma lactate concentration as a predictor of gastric necrosis and survival among dogs with gastric dilatation-volvulus: 102 cases (1995-1998).

PubMed

de Papp, E; Drobatz, K J; Hughes, D

1999-07-01

To determine relationships between plasma lactate concentration and gastric necrosis and between plasma lactate concentration and outcome for dogs with gastric dilatation-volvulus. Retrospective study. 102 dogs. Information on signalment, history, plasma lactate concentration, medical and surgical treatment, cost of hospitalization, and outcome was retrieved from medical records. 69 of 70 (99%) dogs with plasma lactate concentration < 6.0 mmol/L survived, compared with 18 of 31 (58%) dogs with plasma lactate concentration > 6.0 mmol/L (1 dog euthanatized for economic reasons was not included). Gastric necrosis was identified in 38 (37%) dogs. Median plasma lactate concentration in dogs with gastric necrosis (6.6 mmol/L) was significantly higher than concentration in dogs without gastric necrosis (3.3 mmol/L). Specificity and sensitivity of using plasma lactate concentration (with a cutoff of 6.0 mmol/L) to predict which dogs had gastric necrosis were 88 and 61%, respectively. Sixty-two of 63 (98%) dogs without gastric necrosis survived, compared with 25 of 38 (66%) dogs with gastric necrosis. Preoperative plasma lactate concentration was a good predictor of gastric necrosis and outcome for dogs with GDV. Preoperative measurement of plasma lactate concentration may assist in determining prognosis of dogs with GDV.

Prosthetic Mesh Repair in the Emergency Management of Acutely Strangulated Groin Hernias with Grade I Bowel Necrosis: A Rational Choice.

PubMed

Duan, Sheng-Jun; Qiu, Shao-Bo; Ding, Nai-Yong; Liu, Hua-Shui; Zhang, Nai-Shun; Wei, Ying-Tian

2018-02-01

The aim of this study was to determine the feasibility of prosthetic mesh repair according to the degree of bowel necrosis in the emergency management of acutely strangulated groin hernias. Emergency prosthetic mesh repair versus primary suture repair was randomly performed in 208 consecutive strangulated groin hernia patients with bowel necrosis between January 2005 and August 2016. The degree of bowel necrosis of each patient was determined according to a modified three-grade classification system. Patient characteristics sorted by repair method were analyzed by using Pearson's chi-squared tests. Correlations between mortality and wound-related morbidity with bowel necrosis grade and repair method were analyzed. There was no difference in gender, age, body mass index, comorbid diseases, hernia type (left or right, primary or recurrent), necrosis grade, and mortality between the mesh repair and suture repair groups (all P > 0.05). However, with regard to wound-related morbidity, there was significant difference between the two groups (P < 0.05). Mortality and wound-related morbidity showed significant relationship with necrosis grade, especially with regard to postoperative wound infection (P < 0.001). The wound infection rate with mesh repair was significantly higher than that with primary suture in Grade II and III necrosis patients (P < 0.05), but there was no difference in Grade I patients (P > 0.05). The use of prosthetic mesh in the emergency repair of acutely strangulated groin hernias seems to be as safe as suture-only repair in patients with noninfected strangulated bowel (Grade I necrosis). The use of prosthetic mesh repair is a rational choice made based on the degree of bowel necrosis in the emergency management of acutely strangulated hernias.

[Morel-Lavallée syndrome and post-traumatic nodular fat necrosis: Two post-traumatic complications mimicking cellulitis].

PubMed

Moulin, C; Barthélémy, I; Emering, C; D'Incan, M

Dermal and subcutaneous inflammation following direct trauma is initially evocative of soft-tissue infection. However, two differential diagnoses must be considered: Morel-Lavallée syndrome and post-traumatic nodular fat necrosis. Case 1: a 51-year-old woman fell off her motorbike and had dermabrasions on her right and left tibial ridges that rapidly developed into dermo-hypodermitis of the entire limb. There was no improvement after 3 weeks of antibiotics. The patient was apyretic. She had a soft, non-inflammatory tumefaction on the inner aspect of her left knee. Ultrasound revealed subcutaneous collection in both legs. The surgeons confirmed a diagnosis of Morel-Lavallée syndrome and drained the two collections. Progress was good and the patient healed without major consequences. Case 2: following a fall on her stairs, a 40-year-old woman presented dermabrasions and haematomas on her left leg. Antibiotic therapy failed to prevent the progression of dermo-hypodermitis. The patient remained apyretic and there was no inflammatory syndrome. A CT scan showed thickening of a subcutaneous fat and fluid collection, resulting in diagnosis of post-traumatic nodular fat necrosis. Management was surgical and the outcome was good. These two cases show two post-traumatic cutaneous complications: Morel-Lavallée syndrome and post-traumatic nodular fat necrosis. Morel-Lavallée syndrome occurs after tangential trauma next to richly vascularized tissue. Post-traumatic nodular fat necrosis is defined as necrosis of adipocytes. In both cases, diagnosis is confirmed by imagery (Ultrasonography, tomography). Our two case reports show that inflammatory presentation of both Morel-Lavallée syndrome and post-traumatic nodular fat necrosis can lead to diagnostic and therapeutic errors while a surgical procedure is necessary since tissue necrosis can occur. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Receptor Interactive Protein Kinase 3 Promotes Cisplatin-Triggered Necrosis in Apoptosis-Resistant Esophageal Squamous Cell Carcinoma Cells

PubMed Central

Zhao, Nan; Zhou, Lanping; Liu, Fang; Cichacz, Zbigniew; Zhang, Lin; Zhan, Qimin; Zhao, Xiaohang

2014-01-01

Cisplatin-based chemotherapy is currently the standard treatment for locally advanced esophageal cancer. Cisplatin has been shown to induce both apoptosis and necrosis in cancer cells, but the mechanism by which programmed necrosis is induced remains unknown. In this study, we provide evidence that cisplatin induces necrotic cell death in apoptosis-resistant esophageal cancer cells. This cell death is dependent on RIPK3 and on necrosome formation via autocrine production of TNFα. More importantly, we demonstrate that RIPK3 is necessary for cisplatin-induced killing of esophageal cancer cells because inhibition of RIPK1 activity by necrostatin or knockdown of RIPK3 significantly attenuates necrosis and leads to cisplatin resistance. Moreover, microarray analysis confirmed an anti-apoptotic molecular expression pattern in esophageal cancer cells in response to cisplatin. Taken together, our data indicate that RIPK3 and autocrine production of TNFα contribute to cisplatin sensitivity by initiating necrosis when the apoptotic pathway is suppressed or absent in esophageal cancer cells. These data provide new insight into the molecular mechanisms underlying cisplatin-induced necrosis and suggest that RIPK3 is a potential marker for predicting cisplatin sensitivity in apoptosis-resistant and advanced esophageal cancer. PMID:24959694

The ORF1 Products of Tombusviruses Play a Crucial Role in Lethal Necrosis of Virus-Infected Plants

PubMed Central

Burgyán, József; Hornyik, Csaba; Szittya, György; Silhavy, Dániel; Bisztray, György

2000-01-01

Hybrids of cymbidium ringspot (CymRSV) and carnation Italian ringspot (CIRV) tombusviruses were used to identify viral symptom determinants responsible for the generalized necrosis in tombusvirus-infected plants. Surprisingly, symptoms of Nicotiana benthamiana infected with CymRSV/CIRV hybrids were distinctly different. It was demonstrated that not all chimeras expressing wild-type (wt) levels of p19 protein caused systemic necrosis as both parents CymRSV and CIRV did. We showed here that hybrids containing chimeric ORF1 were not able to induce lethal necrosis even if the viral replication of these constructs was not altered significantly. However, if a wt p33 (product of ORF1) of CymRSV was provided in trans in transgenic plants expressing p33 and its readthrough product p92, the lethal necrosis characteristic to tombusvirus infection was restored. In addition, the expression of p33 by a potato virus X viral vector in N. benthamiana caused severe chlorosis and occasionally necrosis, indicating the importance of p33 in wt symptoms of tombusviruses. Thus, our results provide evidence that elicitation of the necrotic phenotype requires the presence of the wt p33 in addition to the p19 protein of tombusviruses. PMID:11069981

Viral erythrocytic necrosis: Some physiological consequences of infection in chum salmon (Oncorhynchus keta)

USGS Publications Warehouse

MacMillan, John R.; Mulcahy, Daniel M.; Landolt, Marsha L.

1980-01-01

Erythroid cells in chum salmon (Oncorhynchus keta) susceptible to infection with erythrocytic necrosis virus (ENV) were examined by light and electron microscopy. Cells of stages II, III, IV, V, and VI contained complete eyrthrocytic necrosis virions in the cytoplasm. Viruses closely resembling ENV were also detected in the nuclei of some erythroblasts. Some secondary consequences of ENV infection were a threefold greater mortality rate from vibriosis, a significantly decreased tolerance to oxygen depletion, and a decreased ability to regulate serum sodium and potassium in saltwater.

Phosphorus Necrosis of the Jaw: A Present-day Study

PubMed Central

Hughes, J. P. W.; Baron, R.; Buckland, D. H.; Cooke, M. A.; Craig, J. D.; Duffield, D. P.; Grosart, A. W.; Parkes, P. W. J.; Porter, A.

1962-01-01

A historical note on the aetiology of phossy jaw shows that present-day knowledge is little greater than it was a century ago. The varied clinical course of the disease is described together with a report of 10 classical cases not previously reported. Six cases, not amounting to true necrosis but in which healing after dental extraction was delayed, and described, and mention is made of the noticeable differences in the oral state and appearances of tartar of healthy workmen exposed to phosphorus compared with healthy workmen not exposed. But no systematic differences of any kind were found in the incidence of general infections, fractures of bones, haematological findings, and biochemical studies of blood and urine in two groups of healthy men most exposed and least exposed to phosphorous in the same factory. An intensive study in hospital of a case of classical necrosis showed no departure from normal, except delayed healing following bone biopsy from the iliac crest, and a reversed polymorphonuclear/lymphocyte ratio. In the discussion the time of onset of necrosis after first exposure to phosphorus, clinical and radiological diagnosis, the organisms present, personal susceptibility, the appearance of the sequestra, and regeneration of bone are considered. An up-to-date note on prevention of the disease is given, although this has met with only partial success. Some persons are highly susceptible and, whilst complete protection is impossible in the light of our present knowledge, early diagnosis and modern treatment have robbed the disease of its terrible manifestations of Victorian times and turned it into a minor, although often uncomfortable complaint, with little or no resulting disability. Images PMID:14449812

Sarcoidosis as an adverse effect of tumor necrosis factor inhibitors.

PubMed

Cathcart, Shelley; Sami, Naveed; Elewski, Boni

2012-05-01

Tumor necrosis factor inhibitors are valuable tools for dermatologists. As their use increases, rare adverse events are more likely to be encountered. We describe one patient who developed sarcoidosis while being treated for psoriasis with etanercept. We sought to review to previously reported cases and further characterize the nature of this reaction. A literature search was performed with the key words "sarcoidosis, sarcoid, etanercept, infliximab, adalimumab, granulomatous, and drug reaction." All relevant cases in the English language were included and evaluated for demographic data, duration of therapy prior to developing sarcoid, duration of sarcoid signs/symptoms, treatments used and time to resolution after discontinuation of the drug. Including the present case, there are 34 cases of sarcoidosis developing during anti-tumor necrosis factor therapy. All previously reported cases were patients with a primarily rheumatologic diagnosis. In all but one case, discontinuation of the drug resulted in complete resolution of symptoms. The lung and surrounding lymph nodes were the areas most commonly affected. The average amount of time between initiation of therapy and onset of symptoms was 22 months. The average time to resolution of symptoms after discontinuation of the drug was 5.2 months. This is a retrospective case review. These data indicated that sarcoid is a possible adverse effect of tumor necrosis factor inhibitor therapy that should be noted by dermatologists using these drugs. While it has been reported in the rheumatology literature, it may be under-recognized by dermatologists.

Methotrexate-induced epidermal necrosis: A case series of 24 patients.

PubMed

Chen, Ting-Jui; Chung, Wen-Hung; Chen, Chun-Bing; Hui, Rosaline Chung-Yee; Huang, Yu-Huei; Lu, Yueh-Tsung; Wang, Chang-Wei; Wang, Kuo-Hsien; Yang, Li-Cheng; Hung, Shuen-Iu

2017-08-01

Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To investigate the clinicopathology, risk factors, and prognostic factors of MEN. We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. The study was limited by the small sample size. MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Immunoexpression of p16 in uterine leiomyomas with infarct-type necrosis: an analysis of 35 cases.

PubMed

Ip, Philip P; Lim, Diana; Cheung, Annie N Y; Oliva, Esther

2017-11-01

Uterine leiomyosarcomas frequently show p16 immunoexpression. However, p16 may also be expressed in some benign leiomyoma variants such as leiomyomas with bizarre nuclei and cellular leiomyomas, limiting its utility as a biomarker to distinguish between benign and malignant neoplasms. We investigated p16 expression in leiomyomas with infarct-type necrosis, tumours which may sometimes be misinterpreted as smooth muscle tumours of uncertain malignant potential or even leiomyosarcoma on conventional light microscopy. p16 immunostaining was performed on 35 leiomyomas with infarct-type necrosis and the staining pattern was analysed. Staining was classified as absent, scattered/isolated, <33-, 33-66- or >66%-positive cells, and was assessed in the areas immediately surrounding and distant from the infarct. The median age of patients was 44 years. Seventeen had hormonal/non-hormonal drugs and three were pregnant. The median tumour size was 7.25 cm. The mean mitotic count was 0.9/10 high-power fields. Only one tumour had multifocal mild nuclear atypia. Positive p16 was noted in 34 of 35 (97.2%) tumours. It was typically patchy, and was concentrated in areas immediately surrounding the necrosis. Distant from the necrosis, p16 positivity was seen predominantly in scattered/isolated cells. One tumour without any worrisome microscopic features showed diffuse p16 positivity throughout. Median follow-up was 55 months, and none of the patients experienced any recurrence. p16 expression in benign uterine smooth muscle tumours with infarct-type necrosis is common. The staining is particularly concentrated adjacent to areas of necrosis. It is important to be aware of this potential pitfall when interpreting p16 expression. © 2017 John Wiley & Sons Ltd.

Pro-inflammatory proteins S100A9 and tumor necrosis factor-α suppress erythropoietin elaboration in myelodysplastic syndromes.

PubMed

Cluzeau, Thomas; McGraw, Kathy L; Irvine, Brittany; Masala, Erico; Ades, Lionel; Basiorka, Ashley A; Maciejewski, Jaroslaw; Auberger, Patrick; Wei, Sheng; Fenaux, Pierre; Santini, Valeria; List, Alan

2017-12-01

Accumulating evidence implicates innate immune activation in the pathobiology of myelodysplastic syndromes. A key myeloid-related inflammatory protein, S100A9, serves as a Toll-like receptor ligand regulating tumor necrosis factor-α and interleukin-1β production. The role of myelodysplastic syndrome-related inflammatory proteins in endogenous erythropoietin regulation and response to erythroid-stimulating agents or lenalidomide has not been investigated. The HepG2 hepatoma cell line was used to investigate in vitro erythropoietin elaboration. Serum samples collected from 311 patients with myelodysplastic syndrome were investigated (125 prior to treatment with erythroid-stimulating agents and 186 prior to lenalidomide therapy). Serum concentrations of S100A9, S100A8, tumor necrosis factor-α, interleukin-1β and erythropoietin were analyzed by enzyme-linked immunosorbent assay. Using erythropoietin-producing HepG2 cells, we show that S100A9, tumor necrosis factor-α and interleukin-1β suppress transcription and cellular elaboration of erythropoietin. Pre-incubation with lenalidomide significantly diminished suppression of erythropoietin production by S100A9 or tumor necrosis factor-α. Moreover, in peripheral blood mononuclear cells from patients with myelodysplastic syndromes, lenalidomide significantly reduced steady-state S100A9 generation ( P =0.01) and lipopolysaccharide-induced tumor necrosis factor-α elaboration ( P =0.002). Enzyme-linked immunosorbent assays of serum from 316 patients with non-del(5q) myelodysplastic syndromes demonstrated a significant inverse correlation between tumor necrosis factor-α and erythropoietin concentrations ( P =0.006), and between S100A9 and erythropoietin ( P =0.01). Moreover, baseline serum tumor necrosis factor-α concentration was significantly higher in responders to erythroid-stimulating agents ( P =0.03), whereas lenalidomide responders had significantly lower tumor necrosis factor-α and higher S100A9 serum

Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection

PubMed Central

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

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…

Acute esophageal necrosis and liver pathology, a rare combination

PubMed Central

Khan, Amir Maqbul; Hundal, Rangit; Ramaswamy, Vijaya; Korsten, Mark; Dhuper, Sunil

2004-01-01

Acute esophageal necrosis (AEN) or “black esophagus” is a clinical condition found at endoscopy. It is a rare entity the exact etiology of which remains unknown. We describe a case of ‘black esophagus’, first of its kind, in the setting of liver cirrhosis and hepatic encephalopathy. PMID:15285044

Increased DNA damage and increased apoptosis and necrosis in patients with severe sepsis and septic shock.

PubMed

Bahar, Ilhan; Elay, Gülseren; Başkol, Gulden; Sungur, Murat; Donmez-Altuntas, Hamiyet

2018-02-01

Reactive oxygen species (ROS) has a key role in the pathogenesis of sepsis. We wanted to evaluate ROS-associated lymphocyte necrosis and apoptosis. A total of 51 patients were included in the study, 29 in the patient group and 22 in the control group. Blood samples were taken from patients in the patient group during severe sepsis or septic shock, then again once they had recovered. Oxidative DNA damage was evaluated by 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Peripheral blood lymphocytes from patients were evaluated with a microscope immediately. The rate of apoptosis and necrosis of lymphocytes were evaluated according to the number of cells in the peripheral. The level of 8-OHdG increased with severe sepsis or septic shock. There were significant differences between the pre- and post-treatment values for apoptotic cell frequency (4.21±3.15 vs. 3.82±3.07, P<0.05) and necrotic cell frequency (4.75±3.61 vs. 4.09±3.37, P<0.05). Apoptosis and necrosis was increased during severe sepsis and septic shock, and apoptosis increase also continued after recovery, but necrosis decreased following disease recovery. CONCLUSıONS: In patients with severe sepsis or septic shock, apoptosis and necrosis were increased along with increased 8-OHdG level. Copyright © 2017 Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jost, Sarah C.; Hope, Andrew; Kiehl, Erich

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 progressivemore » 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.« less

Inhibition of iron overload-induced apoptosis and necrosis of bone marrow mesenchymal stem cells by melatonin.

PubMed

Yang, Fan; Li, Yuan; Yan, Gege; Liu, Tianyi; Feng, Chao; Gong, Rui; Yuan, Ye; Ding, Fengzhi; Zhang, Lai; Idiiatullina, Elina; Pavlov, Valentin; Han, Zhenbo; Ma, Wenya; Huang, Qi; Yu, Ying; Bao, Zhengyi; Wang, Xiuxiu; Hua, Bingjie; Du, Zhimin; Cai, Benzhi; Yang, Lei

2017-05-09

Iron overload induces severe damage to several vital organs such as the liver, heart and bone, and thus contributes to the dysfunction of these organs. The aim of this study is to investigate whether iron overload causes the apoptosis and necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent its toxicity. Perls' Prussion blue staining showed that exposure to increased concentrations of ferric ammonium citrate (FAC) induced a gradual increase of intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC decreased the viability of BMSCs in a concentration-dependent manner. Notably, melatonin protected BMSCs against apoptosis and necrosis induced by FAC and it was vertified by Live/Dead, TUNEL and PI/Hoechst stainings. Furthermore, melatonin pretreatment suppressed FAC-induced reactive oxygen species accumulation. Western blot showed that exposure to FAC resulted in the decrease of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bax and Cleaved Caspase-3, and necrosis-related proteins RIP1 and RIP3, which were significantly inhibited by melatonin treatment. At last, melatonin receptor blocker luzindole failed to block the protection of BMSCs apoptosis and necrosis by melatonin. Taken together, melatonin protected BMSCs from iron overload induced apoptosis and necrosis by regulating Bcl-2, Bax, Cleaved Caspase-3, RIP1 and RIP3 pathways.

Inhibition of iron overload-induced apoptosis and necrosis of bone marrow mesenchymal stem cells by melatonin

PubMed Central

Yan, Gege; Liu, Tianyi; Feng, Chao; Gong, Rui; Yuan, Ye; Ding, Fengzhi; Zhang, Lai; Idiiatullina, Elina; Pavlov, Valentin; Han, Zhenbo; Ma, Wenya; Huang, Qi; Yu, Ying; Bao, Zhengyi; Wang, Xiuxiu; Hua, Bingjie; Du, Zhimin; Cai, Benzhi; Yang, Lei

2017-01-01

Iron overload induces severe damage to several vital organs such as the liver, heart and bone, and thus contributes to the dysfunction of these organs. The aim of this study is to investigate whether iron overload causes the apoptosis and necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent its toxicity. Perls’ Prussion blue staining showed that exposure to increased concentrations of ferric ammonium citrate (FAC) induced a gradual increase of intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC decreased the viability of BMSCs in a concentration-dependent manner. Notably, melatonin protected BMSCs against apoptosis and necrosis induced by FAC and it was vertified by Live/Dead, TUNEL and PI/Hoechst stainings. Furthermore, melatonin pretreatment suppressed FAC-induced reactive oxygen species accumulation. Western blot showed that exposure to FAC resulted in the decrease of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bax and Cleaved Caspase-3, and necrosis-related proteins RIP1 and RIP3, which were significantly inhibited by melatonin treatment. At last, melatonin receptor blocker luzindole failed to block the protection of BMSCs apoptosis and necrosis by melatonin. Taken together, melatonin protected BMSCs from iron overload induced apoptosis and necrosis by regulating Bcl-2, Bax, Cleaved Caspase-3, RIP1 and RIP3 pathways. PMID:28415572

Necrosis predicts benefit from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III randomised trial☆

PubMed Central

Eustace, Amanda; Irlam, Joely J.; Taylor, Janet; Denley, Helen; Agrawal, Shailesh; Choudhury, Ananya; Ryder, David; Ord, Jonathan J.; Harris, Adrian L.; Rojas, Ana M.; Hoskin, Peter J.; West, Catharine M.L.

2013-01-01

Background and purpose Addition of carbogen and nicotinamide (hypoxia-modifying agents) to radiotherapy improves the survival of patients with high risk bladder cancer. The study investigated whether histopathological tumour features and putative hypoxia markers predicted benefit from hypoxia modification. Materials and methods Samples were available from 231 patients with high grade and invasive bladder carcinoma from the BCON phase III trial of radiotherapy (RT) alone or with carbogen and nicotinamide (RT + CON). Histopathological tumour features examined were: necrosis, growth pattern, growing margin, and tumour/stroma ratio. Hypoxia markers carbonic anhydrase-IX and glucose transporter-1 were examined using tissue microarrays. Results Necrosis was the only independent prognostic indicator (P = 0.04). Necrosis also predicted benefit from hypoxia modification. Five-year overall survival was 48% (RT) versus 39% (RT + CON) (P = 0.32) in patients without necrosis and 34% (RT) versus 56% (RT + CON) (P = 0.004) in patients with necrosis. There was a significant treatment by necrosis strata interaction (P = 0.001 adjusted). Necrosis was an independent predictor of benefit from RT + CON versus RT (hazard ratio [HR]: 0.43, 95% CI 0.25–0.73, P = 0.002). This trend was not observed when there was no necrosis (HR: 1.64, 95% CI 0.95–2.85, P = 0.08). Conclusions Necrosis predicts benefit from hypoxia modification in patients with high risk bladder cancer and should be used to select patients; it is simple to identify and easy to incorporate into routine histopathological examination. PMID:23773411

Surgical techniques in radiation induced temporal lobe necrosis in nasopharyngeal carcinoma patients.

PubMed

Alfotih, Gobran Taha Ahmed; Zheng, Mei Guang; Cai, Wang Qing; Xu, Xin Ke; Hu, Zhen; Li, Fang Cheng

2016-01-01

Radiation induced brain injury ranges from acute reversible edema to late, irreversible radiation necrosis. Radiation induced temporal lobe necrosis is associated with permanent neurological deficits and occasionally progresses to death. We present our experience with surgery on radiation induced temporal lobe necrosis (RTLN) in nasopharyngeal carcinoma (NPC) patients with special consideration of clinical presentation, surgical technique, and outcomes. This retrospective study includes 12 patients with RTLN treated by the senior author between January 2010 and December 2014. Patients initially sought medical treatment due to headache; other symptoms were hearing loss, visual deterioration, seizure, hemiparesis, vertigo, memory loss and agnosia. A temporal approach through a linear incision was performed for all cases. RTLN was found in one side in 7 patients, and bilaterally in 5. 4 patients underwent resection of necrotic tissue bilaterally and 8 patients on one side. No death occurred in this series of cases. There were no post-operative complications, except 1 patient who developed aseptic meningitis. All 12 patients were free from headache. No seizure occurred in patients with preoperative epilepsy. Other symptoms such as hemiparesis and vertigo improved in all patients. Memory loss, agnosia and hearing loss did not change post-operatively in all cases. The follow-up MR images demonstrated no recurrence of necrotic lesions in all 12 patients. Neurosurgical intervention through a temporal approach with linear incision is warranted in patients with radiation induced temporal lobe necrosis with significant symptoms and signs of increased intracranial pressure, minimum space occupying effect on imaging, or neurological deterioration despite conservative management. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

[Short-term curative effects of Tantalum rod treatment in early avascular necrosis].

PubMed

Ye, Fu-Sheng; Ni, Zhe-Ji; Chu, Xiao-Bing; He, Bang-Jian; Li, Ju; Tong, Pei-Jian

2013-08-01

To explore the recent clinical curative effect of Tantalum rod in treating the early avascular necrosis. From January 2008 to November 2008, the 25 patients (39 hips) with early avascular necrosis accepted tantalum rod placement and included 9 males (11 hips) and 16 females (28 hips) with an average age of 37 years old ranging from 18 to 74 years old. Four patients (6 hips) caused by Alcoholic, 6 patients (8 hips) by hormone, 2 cases (2 hips) by traumatic, 13 cases (23 hips) by idiopathic. Steinberg preoperative stage involved 7 hips in period I, 24 hips in period II, 8 hips in period III. Curative effect analysis included preoperative and postoperative Harris score, radiographic changes and hip replacement for follow-up to accept the end of the femoral head survival rate. All patients were followed up for 6 to 47 months (averaged 37.4 months). All 12 hips imaging appeard progress,including tantalum rod exit in 1 hip, hip hemiarthroplasty collapse in 3 hips, the area increased to avascular necrosis in 8 hips. Six hips accepted total hip replacement, including imaging progress in 5 hips (41.7%, 5/12), no imaging progress in 1 hip (3.7%,1/27). All hips' Kaplan-Meier survival curves showed 6-month survival rate was (97.4 +/- 2.5)% after tantalum stick insertion, 1-year survival rate was (94.7 +/- 3.6), and 2-year survival rate was (88.6 +/- 5.4)%, 3-year survival rate was (72.5 +/- 11.2). It is effective for treatment of avascular necrosis of femoral head in Steinberg I and II by Tantalum rod, and it can effectively relieve femoral head replacement time.

Prognostic significance of chemotherapy-induced necrosis in osteosarcoma patients receiving pasteurized autografts

PubMed Central

Joo, Min Wook; Kang, Yong Koo; Yoo, Chang-Young; Cha, Sung Ho

2017-01-01

Background Among various reconstruction methods after wide excision for osteosarcoma, pasteurized autograft is often preferred. While the whole area of the tumor can be assessed for chemotherapy-induced necrosis, one of the important prognostic factors, in other reconstructive techniques, only a portion removed from a wide-resection specimen is available when using pasteurized autograft method. The assessment, therefore, may be unreliable. We analyzed the prognostic significance of the chemotherapy-induced necrosis in osteosarcoma patients who underwent reconstruction with pasteurized autografts. Patients and methods We reviewed the records of osteosarcoma patients who underwent treatment in our institution from 1998 to 2013. Cases of reconstruction with pasteurized autografts were defined as the patient group, and the same number of patients who underwent other reconstruction methods served as controls. Chemotherapy-induced necrosis was evaluated for removed extra-osseous and curetted intramedullary tumor tissues. Results A total of 22 patients were identified; the median age was 15.5 years, and there were 12 males. The most common tumor location was the distal femur. The most common histological subtype was osteoblastic. Median size was 8.1 cm. Disease status was stage IIB in 13 patients and IIA in 9. Median follow-up was 76 months. No differences between the patient and control groups were observed in potential prognostic factors, overall survival, metastasis-free survival, or recurrence-free survival. Univariate analyses demonstrated that histological response was a significant prognostic factor for metastasis-free survival and also significant for recurrence-free survival. Conclusion Chemotherapy-induced necrosis grading, using only available tumor tissues, could be a prognostic factor for osteosarcoma patients receiving pasteurized autografts for reconstructive surgery. PMID:28196121

Proactive infectious disease approach to dermatologic patients who are taking tumor necrosis factor-alfa antagonists: Part I. Risks associated with tumor necrosis factor-alfa antagonists.

PubMed

Chirch, Lisa M; Cataline, Philip R; Dieckhaus, Kevin D; Grant-Kels, Jane M

2014-07-01

Tumor necrosis factor-alfa levels are linked to disease severity in patients with inflammatory conditions, such as psoriasis. Inhibitors of this cytokine are commonly used with significant success in the treatment of such inflammatory disorders. Their use, however, can be plagued by infectious complications. An awareness of potential infections associated with these therapies is critical in order to maximize preventive efforts both before and during therapy. This review provides a guide for dermatologists caring for patients in need of this type of biologic therapy to preemptively address the infectious risks. Part I of this continuing medical education article reviews background information on the various infectious risks associated with tumor necrosis factor inhibitor therapy and appropriate historical data to obtain in the context of pretherapy evaluations. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Rin4 Causes Hybrid Necrosis and Race-Specific Resistance in an Interspecific Lettuce Hybrid[W

PubMed Central

Jeuken, Marieke J.W.; Zhang, Ningwen W.; McHale, Leah K.; Pelgrom, Koen; den Boer, Erik; Lindhout, Pim; Michelmore, Richard W.; Visser, Richard G.F.; Niks, Rients E.

2009-01-01

Some inter- and intraspecific crosses may result in reduced viability or sterility in the offspring, often due to genetic incompatibilities resulting from interactions between two or more loci. Hybrid necrosis is a postzygotic genetic incompatibility that is phenotypically manifested as necrotic lesions on the plant. We observed hybrid necrosis in interspecific lettuce (Lactuca sativa and Lactuca saligna) hybrids that correlated with resistance to downy mildew. Segregation analysis revealed a specific allelic combination at two interacting loci to be responsible. The allelic interaction had two consequences: (1) a quantitative temperature-dependent autoimmunity reaction leading to necrotic lesions, lethality, and quantitative resistance to an otherwise virulent race of Bremia lactucae; and (2) a qualitative temperature-independent race-specific resistance to an avirulent race of B. lactucae. We demonstrated by transient expression and silencing experiments that one of the two interacting genes was Rin4. In Arabidopsis thaliana, RIN4 is known to interact with multiple R gene products, and their interactions result in hypersensitive resistance to Pseudomonas syringae. Site-directed mutation studies on the necrosis-eliciting allele of Rin4 in lettuce showed that three residues were critical for hybrid necrosis. PMID:19855048

Permanent renal loss following tumor necrosis factor α antagonists for arthritis.

PubMed

Chen, Tzu-Jen; Yang, Ya-Fei; Huang, Po-Hao; Lin, Hsin-Hung; Huang, Chiu-Ching

2010-06-01

Tumor necrosis factor alpha (TNF-alpha) antagonists are now widely used in the treatment of aggressive rheumatoid arthritis and are generally well tolerated. Although rare, they could induce systemic lupus erythematosus, glomerulonephritis, and antineutrophil cytoplasmic antibody associated systemic vasculitis. Tumor necrosis factor alpha antagonists associated glomerulonephritis usually subsides after discontinuation of the therapy and subsequent initiation of corticosteroids and immunosuppressive agents. Here we describe crescentic glomerulonephritis progression to end-stage renal disease in a patient following two doses of TNF-alpha antagonists for the treatment of reactive arthritis. To our knowledge, dialysis dependent permanent renal loss after TNF-alpha antagonists has not yet been reported. We suggest the renal function should be closely monitored in patients treated with TNF-alpha antagonists by rheumatologists.

Adenosine triphosphate hydrolysis reduces neutrophil infiltration and necrosis in partial-thickness scald burns in mice.

PubMed

Bayliss, Jill; Delarosa, Sara; Wu, Jianfeng; Peterson, Jonathan R; Eboda, Oluwatobi N; Su, Grace L; Hemmila, Mark; Krebsbach, Paul H; Cederna, Paul S; Wang, Stewart C; Xi, Chuanwu; Levi, Benjamin

2014-01-01

Extracellular adenosine triphosphate (ATP), present in thermally injured tissue, modulates the inflammatory response and causes significant tissue damage. The authors hypothesize that neutrophil infiltration and ensuing tissue necrosis would be mitigated by removing ATP-dependent signaling at the burn site. Mice were subjected to 30% TBSA partial-thickness scald burn by dorsal skin immersion in a water bath at 60 or 20°C (nonburn controls). In the treatment arm, an ATP hydrolyzing enzyme, apyrase, was applied directly to the site immediately after injury. Skin was harvested after 24 hours and 5 days for hematoxylin and eosin stain, elastase, and Ki-67 staining. Tumor necrosis factor (TNF)-α and interferon (IFN)-β expression were measured through quantitative real-time polymerase chain reaction. At 24 hours, the amount of neutrophil infiltration was different between the burn and burn + apyrase groups (P < .001). Necrosis was less extensive in the apyrase group when compared with the burn group at 24 hours and 5 days. TNF-α and IFN-β expression at 24 hours in the apyrase group was lower than in the burn group (P < .05). However, Ki-67 signaling was not significantly different among the groups. The results of this study support the role of extracellular ATP in neutrophil activity. The authors demonstrate that ATP hydrolysis at the burn site allays the neutrophil response to thermal injury and reduces tissue necrosis. This decrease in inflammation and tissue necrosis is at least partially because of TNF-α and IFN-β signaling. Apyrase could be used as topical inflammatory regulators to quell the injury caused by inflammation.

[Pathological changes of the blood vessels in rabbit femoral head with glucocorticoid-induced necrosis].

PubMed

Hu, Zhi-ming; Wang, Hai-bin; Zhou, Ming-qian; Yao, Xin-sheng; Ma, Li; Wang, Xiao-ning

2006-06-01

To observe the pathological changes in the blood vessels in rabbit femoral head with glucocorticoid-induced necrosis and investigate the pathogenesis of glucocorticoid-induced osteonecrosis. Twenty New Zealand white rabbits were randomly divided into two groups, namely group A. which was injected with horse serum and prednisone and group B as the control group. Chinese ink was injected into the femoral cavity of the rabbits to observe the blood vessels in the femoral head under optical microscope and the femoral head was examined histopathologically. Compared with the normal control group, the rabbits in group A had significantly decreased number of perfused vessels, which was featured by defective perfusion, osteocytie pyknosis or necrosis, increase of empty ostoocyte lacunae and fat cells, decrease of hematopoietic tissue, and blood vessel occlusion. Vascular occlusion and vasculitis due to glucocorticoid treatment may cause avascular necrosis of the femoral head.

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

PubMed

Zhang, Mingjuan; Hu, Xianda

2016-07-01

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 G 0 /G 1 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

[Dekasan application in treatment of infected pancreatic necrosis and its complications].

PubMed

Nichitaĭlo, M E

2010-03-01

The experience of the use of domestic antiseptic dekasan for topical use in patients over the infected pancreatic necrosis and its complications. There was significant improvement in the results of patients treatment.

Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases

PubMed Central

Thapa, Roshan J.; Nogusa, Shoko; Chen, Peirong; Maki, Jenny L.; Lerro, Anthony; Andrake, Mark; Rall, Glenn F.; Degterev, Alexei; Balachandran, Siddharth

2013-01-01

Interferons (IFNs) are cytokines with powerful immunomodulatory and antiviral properties, but less is known about how they induce cell death. Here, we show that both type I (α/β) and type II (γ) IFNs induce precipitous receptor-interacting protein (RIP)1/RIP3 kinase-mediated necrosis when the adaptor protein Fas-associated death domain (FADD) is lost or disabled by phosphorylation, or when caspases (e.g., caspase 8) are inactivated. IFN-induced necrosis proceeds via progressive assembly of a RIP1–RIP3 “necrosome” complex that requires Jak1/STAT1-dependent transcription, but does not need the kinase activity of RIP1. Instead, IFNs transcriptionally activate the RNA-responsive protein kinase PKR, which then interacts with RIP1 to initiate necrosome formation and trigger necrosis. Although IFNs are powerful activators of necrosis when FADD is absent, these cytokines are likely not the dominant inducers of RIP kinase-driven embryonic lethality in FADD-deficient mice. We also identify phosphorylation on serine 191 as a mechanism that disables FADD and collaborates with caspase inactivation to allow IFN-activated necrosis. Collectively, these findings outline a mechanism of IFN-induced RIP kinase-dependent necrotic cell death and identify FADD and caspases as negative regulators of this process. PMID:23898178

Doxorubicin-induced necrosis is mediated by poly-(ADP-ribose) polymerase 1 (PARP1) but is independent of p53.

PubMed

Shin, Hyeon-Jun; Kwon, Hyuk-Kwon; Lee, Jae-Hyeok; Gui, Xiangai; Achek, Asma; Kim, Jae-Ho; Choi, Sangdun

2015-11-02

Necrosis, unregulated cell death, is characterized by plasma membrane rupture as well as nuclear and cellular swelling. However, it has recently been reported that necrosis is a regulated form of cell death mediated by poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is thought to mediate necrosis by inducing DNA damage, although this remains unconfirmed. In this study, we examined the mechanisms of PARP1-mediated necrosis following doxorubicin (DOX)-induced DNA damage in human kidney proximal tubular (HK-2) cells. DOX initiated DNA damage response (DDR) and upregulated PARP1 and p53 expression, resulting in morphological changes similar to those observed during necrosis. Additionally, DOX induced mitochondrial hyper-activation, as evidenced by increased mitochondrial respiration and cytosolic ATP (cATP) production. However, DOX affected mitochondrial mass. DOX-induced DNA damage, cytosolic reactive oxygen species (cROS) generation, and mitochondrial hyper-activation decreased in cells with inhibited PARP1 expression, while generation of nitric oxide (NO) and mitochondrial ROS (mROS) remained unaffected. Moreover, DOX-induced DNA damage, cell cycle changes, and oxidative stress were not affected by p53 inhibition. These findings suggest that DNA damage induced necrosis through a PARP1-dependent and p53-independent pathway.

Doxorubicin-induced necrosis is mediated by poly-(ADP-ribose) polymerase 1 (PARP1) but is independent of p53

PubMed Central

Shin, Hyeon-Jun; Kwon, Hyuk-Kwon; Lee, Jae-Hyeok; Gui, Xiangai; Achek, Asma; Kim, Jae-Ho; Choi, Sangdun

2015-01-01

Necrosis, unregulated cell death, is characterized by plasma membrane rupture as well as nuclear and cellular swelling. However, it has recently been reported that necrosis is a regulated form of cell death mediated by poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is thought to mediate necrosis by inducing DNA damage, although this remains unconfirmed. In this study, we examined the mechanisms of PARP1-mediated necrosis following doxorubicin (DOX)-induced DNA damage in human kidney proximal tubular (HK-2) cells. DOX initiated DNA damage response (DDR) and upregulated PARP1 and p53 expression, resulting in morphological changes similar to those observed during necrosis. Additionally, DOX induced mitochondrial hyper-activation, as evidenced by increased mitochondrial respiration and cytosolic ATP (cATP) production. However, DOX affected mitochondrial mass. DOX-induced DNA damage, cytosolic reactive oxygen species (cROS) generation, and mitochondrial hyper-activation decreased in cells with inhibited PARP1 expression, while generation of nitric oxide (NO) and mitochondrial ROS (mROS) remained unaffected. Moreover, DOX-induced DNA damage, cell cycle changes, and oxidative stress were not affected by p53 inhibition. These findings suggest that DNA damage induced necrosis through a PARP1-dependent and p53-independent pathway. PMID:26522181

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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. 2015 BMJ Publishing Group Ltd.

Differentiating tumor recurrence from treatment necrosis: a review of neuro-oncologic imaging strategies

PubMed Central

Verma, Nishant; Cowperthwaite, Matthew C.; Burnett, Mark G.; Markey, Mia K.

2013-01-01

Abstract Differentiating treatment-induced necrosis from tumor recurrence is a central challenge in neuro-oncology. These 2 very different outcomes after brain tumor treatment often appear similarly on routine follow-up imaging studies. They may even manifest with similar clinical symptoms, further confounding an already difficult process for physicians attempting to characterize a new contrast-enhancing lesion appearing on a patient's follow-up imaging. Distinguishing treatment necrosis from tumor recurrence is crucial for diagnosis and treatment planning, and therefore, much effort has been put forth to develop noninvasive methods to differentiate between these disparate outcomes. In this article, we review the latest developments and key findings from research studies exploring the efficacy of structural and functional imaging modalities for differentiating treatment necrosis from tumor recurrence. We discuss the possibility of computational approaches to investigate the usefulness of fine-grained imaging characteristics that are difficult to observe through visual inspection of images. We also propose a flexible treatment-planning algorithm that incorporates advanced functional imaging techniques when indicated by the patient's routine follow-up images and clinical condition. PMID:23325863

Idiopathic and diabetic skeletal muscle necrosis: evaluation by magnetic resonance imaging.

PubMed

Kattapuram, Taj M; Suri, Rajeev; Rosol, Michael S; Rosenberg, Andrew E; Kattapuram, Susan V

2005-04-01

Idiopathic and diabetic-associated muscle necrosis are similar, uncommon clinical entities requiring conservative management and minimal intervention to avoid complications and prolonged hospitalization. An early noninvasive diagnosis is therefore essential. We evaluated the magnetic resonance imaging (MRI) characteristics of muscle necrosis in 14 patients, in eight of whom the diagnoses were confirmed histologically. Two experienced musculoskeletal radiologists performed retrospective evaluations of the MRI studies of 14 patients with the diagnoses of skeletal muscle infarction. In 10 cases gadolinium-enhanced (T1-weighted fat-suppressed) sequences were available along with T1-weighted, T2-weighted images and STIR sequences, while in four cases contrast-enhanced images were not available. Eight patients had underlying diabetes and in six patients the cause of the myonecrosis was considered idiopathic. T1-weighted images demonstrated isointense swelling of the involved muscle, with mildly displaced fascial planes. There was effacement of the fat signal intensity within the muscle. Fat-suppressed T2-weighted images showed diffuse heterogeneous high signal intensity in the muscles suggestive of edema. Perifascial fluid collection was seen in eight cases. Subcutaneous edema was present in seven patients. Following intravenous gadolinium administration, MRI demonstrated a focal area of heterogeneously enhancing mass with peripheral enhancement. Within this focal lesion, linear dark areas were seen with serpentine enhancing streaks separating them in eight cases. In two cases, a central relatively nonenhancing mass with irregular margins and peripheral enhancement was noted. The peripheral enhancement involved a significant part of the muscle. No focal fluid collection was noted. We believe that the constellation of imaging findings on T1- and T2-weighted images and post-gadolinium sequences is highly suggestive of muscle necrosis. We consider certain specific findings

Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study.

PubMed

Watson, Maura A; Baker, Thomas P; Nguyen, Annie; Sebastianelli, Mary E; Stewart, Heather L; Oliver, David K; Abbott, Kevin C; Yuan, Christina M

2012-09-01

Colonic necrosis has been reported after sodium polystyrene sulfonate (SPS)/sorbitol use, but the incidence and relative risk (RR) are not established. Retrospective cohort study. 123,391 adult inpatients at a tertiary medical center. Receipt of SPS prescriptions (exposed) or a prescription other than SPS (unexposed internal comparison group) between September 1, 2001, and October 31, 2010. The main outcome measure was tissue-confirmed diagnosis of colonic necrosis, considered SPS-associated if SPS was prescribed 30 or fewer days before tissue accession date. Demographics, serum chemistry test results, hospital location, and International Classification of Diseases, Ninth Revision diagnostic codes. SPS was prescribed to 2,194 inpatients. 82 inpatient colonic necrosis cases were identified. 3 received oral SPS (1 gram per 4 milliliters of 33% sorbitol) 30 or fewer days before the colonic necrosis accession date (3.7% of inpatient colonic necrosis cases). The data were linked with 123,391 individuals who received inpatient prescriptions between the same dates. Colonic necrosis incidence was 0.14% (95% CI, 0.03%-0.40%) in those prescribed SPS versus 0.07% (95% CI, 0.05-0.08%) in those not prescribed SPS (RR, 2.10; 95% CI, 0.68-6.48; P = 0.2). The number needed to harm was 1,395 (95% CI, 298-5,100). Subgroup analysis (age >65 years; estimated glomerular filtration rate, <30 mL/min/1.73 m(2), intensive care unit admission, or surgical ward status) did not show significant associations. Sample-size analysis indicated that 4,974 SPS-treated individuals older than 65 years and a comparison group 10 times larger would be required for rigorous multivariate analysis of SPS-associated colonic necrosis risk. Individuals with colonic necrosis admitted to non-Department of Defense hospitals would not have been ascertained. Only individuals who had colonic biopsy or surgical tissue submitted for pathologic review could be ascertained as having colonic necrosis. SPS

Dermal necrosis following coumarin: is it immunologically induced?

PubMed

Hislop, I G; Zilko, P J; Petersen, M; Ahmed, N

1980-02-01

Two patients with dermal necrosis due to anticoagulation therapy with warfarin are reported. Both patients demonstrated some disturbance in immunological function. It appears possible that warfarin may act as a hapten in the induction of hypersensitivity to the drug. It is recommended that future cases should be studied to determine whether there is a defect in immunoregulation, and whether circulating immune complexes are responsible for the typical skin lesions.

Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levin, Victor A., E-mail: vlevin49@comcast.ne; Bidaut, Luc; Hou, Ping

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 weeksmore » 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

Necrosis After Craniospinal Irradiation: Results From a Prospective Series of Children With Central Nervous System Embryonal Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, Erin S.; Merchant, Thomas E., E-mail: thomas.merchant@stjude.org; Wu Shengjie

Purpose: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series. Patients and Methods: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy tomore » the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis. Results: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% {+-} 1.3% (n = 236) for the entire cohort and 4.4% {+-} 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: {>=}50 Gy (92.12% {+-} 4.58% vs 72.89% {+-} 1.96%; P=.0337), {>=}52 Gy (88.95% {+-} 5.50% vs 69.16% {+-} 1.97%; P=.0275), and {>=}54 Gy (82.28% {+-} 7.06% vs 63.37% {+-} 1.96%; P=.0488), respectively. Conclusions: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.« less

MutY DNA Glycosylase Protects Cells From Tumor Necrosis Factor Alpha-Induced Necroptosis.

PubMed

Tran, An Hue Vy; Han, Se Hee; Kim, Joon; Grasso, Francesca; Kim, In San; Han, Ye Sun

2017-07-01

Numerous studies have implied that mutY DNA glycosylase (MYH) is involved in the repair of post-replicative mispairs and plays a critical role in the base excision repair pathway. Recent in vitro studies have shown that MYH interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD), a key effector protein of tumor necrosis factor receptor-1 (TNFR1) signaling. The association between MYH and TRADD is reversed during tumor necrosis factor alpha (TNF-α)- and camptothecin (CPT)-induced apoptosis, and enhanced during TNF-α-induced survival. After investigating the role of MYH interacts with various proteins following TNF-α stimulation, here, we focus on MYH and TRADD interaction functions in necroptosis and its effects to related proteins. We report that the level of the MYH and TRADD complex was also reduced during necroptosis induced by TNF-α and zVAD-fmk. In particular, we also found that MYH is a biologically important necrosis suppressor. Under combined TNF-α and zVAD-fmk treatment, MYH-deficient cells were induced to enter the necroptosis pathway but primary mouse embryonic fibroblasts (MEFs) were not. Necroptosis in the absence of MYH proceeds via the inactivation of caspase-8, followed by an increase in the formation of the kinase receptor- interacting protein 1 (RIP1)-RIP3 complex. Our results suggested that MYH, which interacts with TRADD, inhibits TNF-α necroptotic signaling. Therefore, MYH inactivation is essential for necroptosis via the downregulation of caspase-8. J. Cell. Biochem. 118: 1827-1838, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Diagnostic Accuracy of Centrally Restricted Diffusion in the Differentiation of Treatment-Related Necrosis from Tumor Recurrence in High-Grade Gliomas.

PubMed

Zakhari, N; Taccone, M S; Torres, C; Chakraborty, S; Sinclair, J; Woulfe, J; Jansen, G H; Nguyen, T B

2018-02-01

Centrally restricted diffusion has been demonstrated in recurrent high-grade gliomas treated with bevacizumab. Our purpose was to assess the accuracy of centrally restricted diffusion in the diagnosis of radiation necrosis in high-grade gliomas not treated with bevacizumab. In this prospective study, we enrolled patients with high-grade gliomas who developed a new ring-enhancing necrotic lesion and who underwent re-resection. The presence of a centrally restricted diffusion within the ring-enhancing lesion was assessed visually on diffusion trace images and by ADC measurements on 3T preoperative diffusion tensor examination. The percentage of tumor recurrence and radiation necrosis in each surgical specimen was defined histopathologically. The association between centrally restricted diffusion and radiation necrosis was assessed using the Fisher exact test. Differences in ADC and the ADC ratio between the groups were assessed via the Mann-Whitney U test, and receiver operating characteristic curve analysis was performed. Seventeen patients had re-resected ring-enhancing lesions: 8 cases of radiation necrosis and 9 cases of tumor recurrence. There was significant association between centrally restricted diffusion by visual assessment and radiation necrosis ( P = .015) with a sensitivity of 75% and a specificity of 88.9%, a positive predictive value 85.7%, and a negative predictive value of 80% for the diagnosis of radiation necrosis. There was a statistically significant difference in the ADC and ADC ratio between radiation necrosis and tumor recurrence ( P = .027). The presence of centrally restricted diffusion in a new ring-enhancing lesion might indicate radiation necrosis rather than tumor recurrence in high-grade gliomas previously treated with standard chemoradiation without bevacizumab. © 2018 by American Journal of Neuroradiology.

Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis.

PubMed

Bajpai, Jyoti; Gamnagatti, Shivanand; Kumar, Rakesh; Sreenivas, Vishnubhatla; Sharma, Mehar Chand; Khan, Shah Alam; Rastogi, Shishir; Malhotra, Arun; Safaya, Rajni; Bakhshi, Sameer

2011-04-01

Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. Thirty-one treatment-naïve osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response ≥90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma.

Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1

PubMed Central

Yu, Xiaoliang; Li, Yun; Chen, Qin; Su, Chenhe; Zhang, Zili; Yang, Chengkui; Hu, Zhilin; Hou, Jue; Zhou, Jinying; Gong, Ling; Jiang, Xuejun

2015-01-01

ABSTRACT Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. IMPORTANCE This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV. PMID:26559832

Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1.

PubMed

Yu, Xiaoliang; Li, Yun; Chen, Qin; Su, Chenhe; Zhang, Zili; Yang, Chengkui; Hu, Zhilin; Hou, Jue; Zhou, Jinying; Gong, Ling; Jiang, Xuejun; Zheng, Chunfu; He, Sudan

2016-01-15

Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

MRI Evaluation of Post Core Decompression Changes in Avascular Necrosis of Hip.

PubMed

Nori, Madhavi; Marupaka, Sravan Kumar; Alluri, Swathi; Md, Naseeruddin; Irfan, Kazi Amir; Jampala, Venkateshwarlu; Apsingi, Sunil; Eachempati, Krishna Kiran

2015-12-01

Avascular necrosis of hip typically presents in young patients. Core decompression in precollapse stage provides pain relief and preservation of femoral head. The results of core decompression vary considerably despite early diagnosis. The role of MRI in monitoring patients post surgically has not been clearly defined. To study pre and post core decompression MRI changes in avascular necrosis of hip. This is a contiguous observational cohort of 40 hips treated by core decompression for precollapse avascular necrosis of femoral head, who had a baseline MRI performed before surgery. Core decompression of the femoral head was performed within 4 weeks. Follow up radiograph and MRI scans were done at six months. Harris hip score preoperatively, 1 month and 6 months after the surgery was noted. Success in this study was defined as postoperative increase in Harris hip score (HHS) by 20 points and no additional femoral collapse. End point of clinical adverse outcome as defined by fall in Harris hip score was conversion or intention to convert to total hip replacement (THR). MRI parameters in the follow up scan were compared to the preoperative MRI. Effect of core decompression on bone marrow oedema and femoral head collapse was noted. Results were analysed using SPSS software version. Harris hip score improved from 57 to 80 in all patients initially. Six hips had a fall in Harris hip score to mean value of 34.1 during follow up (9 to 12 months) and underwent total hip replacement. MRI predictors of positive outcome are lesions with grade A extent, Grade A & B location. Bone marrow oedema with lesions less than 50% involvement, medial and central location. Careful selection of patients by MR criteria for core decompression provides satisfactory outcome in precollapse stage of avascular necrosis of hip.

MRI Evaluation of Post Core Decompression Changes in Avascular Necrosis of Hip

PubMed Central

Marupaka, Sravan Kumar; Alluri, Swathi; MD, Naseeruddin; Irfan, Kazi Amir; Jampala, Venkateshwarlu; Apsingi, Sunil; Eachempati, Krishna Kiran

2015-01-01

Introduction Avascular necrosis of hip typically presents in young patients. Core decompression in precollapse stage provides pain relief and preservation of femoral head. The results of core decompression vary considerably despite early diagnosis. The role of MRI in monitoring patients post surgically has not been clearly defined. Aim To study pre and post core decompression MRI changes in avascular necrosis of hip. Materials and Methods This is a contiguous observational cohort of 40 hips treated by core decompression for precollapse avascular necrosis of femoral head, who had a baseline MRI performed before surgery. Core decompression of the femoral head was performed within 4 weeks. Follow up radiograph and MRI scans were done at six months. Harris hip score preoperatively, 1 month and 6 months after the surgery was noted. Success in this study was defined as postoperative increase in Harris hip score (HHS) by 20 points and no additional femoral collapse. End point of clinical adverse outcome as defined by fall in Harris hip score was conversion or intention to convert to total hip replacement (THR). MRI parameters in the follow up scan were compared to the preoperative MRI. Effect of core decompression on bone marrow oedema and femoral head collapse was noted. Results were analysed using SPSS software version. Results Harris hip score improved from 57 to 80 in all patients initially. Six hips had a fall in Harris hip score to mean value of 34.1 during follow up (9 to 12 months) and underwent total hip replacement. MRI predictors of positive outcome are lesions with grade A extent, Grade A & B location. Bone marrow oedema with lesions less than 50% involvement, medial and central location. Conclusion Careful selection of patients by MR criteria for core decompression provides satisfactory outcome in precollapse stage of avascular necrosis of hip. PMID:26816966

Idiopathic Avascular Necrosis of First Metatarsal Head in a Pediatric Patient.

PubMed

Kwon, Young-Uk; Choi, Jang-Seok; Kong, Gyu-Min; Ha, Byung-Ho

Idiopathic avascular necrosis of the first metatarsal head rarely occurs in pediatrics. The present case of avascular necrosis of the first metatarsal head occurred in a 13-year-old male who came to the clinic with a 9-month history of pain in the first metatarsophalangeal joint. Conservative treatment had been applied for 9 months, but the pain had not been relieved. Therefore, surgical treatment, including decompression and debridement, was performed in the first metatarsal head of the patient. After 6 months of follow-up monitoring, full range of motion of the first metatarsophalangeal joint was observed, and the pain had disappeared. No any other complications had developed during 18 months of follow-up monitoring. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Membrane-derived second messenger regulates x-ray-mediated tumor necrosis factor alpha gene induction.

PubMed Central

Hallahan, D E; Virudachalam, S; Kuchibhotla, J; Kufe, D W; Weichselbaum, R R

1994-01-01

Cells adapt to adverse environmental conditions through a wide range of responses that are conserved throughout evolution. Physical agents such as ionizing radiation are known to initiate a stress response that is triggered by the recognition of DNA damage. We have identified a signaling pathway involving the activation of phospholipase A2 and protein kinase C in human cells that confers x-ray induction of the tumor necrosis factor alpha gene. Treatment of human cells with ionizing radiation or H2O2 was associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolished radiation-mediated arachidonate production as well as the subsequent activation of protein kinase C and tumor necrosis factor alpha gene expression. These findings demonstrate that ionizing radiation-mediated gene expression in human cells is regulated in part by extranuclear signal transduction. One practical application of phospholipase A2 inhibitors is to ameliorate the adverse effects of radiotherapy associated with tumor necrosis factor alpha production. Images PMID:8197153

Black esophagus: Acute esophageal necrosis syndrome

PubMed Central

Gurvits, Grigoriy E

2010-01-01

Acute esophageal necrosis (AEN), commonly referred to as “black esophagus”, is a rare clinical entity arising from a combination of ischemic insult seen in hemodynamic compromise and low-flow states, corrosive injury from gastric contents in the setting of esophago-gastroparesis and gastric outlet obstruction, and decreased function of mucosal barrier systems and reparative mechanisms present in malnourished and debilitated physical states. AEN may arise in the setting of multiorgan dysfunction, hypoperfusion, vasculopathy, sepsis, diabetic ketoacidosis, alcohol intoxication, gastric volvulus, traumatic transection of the thoracic aorta, thromboembolic phenomena, and malignancy. Clinical presentation is remarkable for upper gastrointestinal bleeding. Notable symptoms may include epigastric/abdominal pain, vomiting, dysphagia, fever, nausea, and syncope. Associated laboratory findings may reflect anemia and leukocytosis. The hallmark of this syndrome is the development of diffuse circumferential black mucosal discoloration in the distal esophagus that may extend proximally to involve variable length of the organ. Classic “black esophagus” abruptly stops at the gastroesophageal junction. Biopsy is recommended but not required for the diagnosis. Histologically, necrotic debris, absence of viable squamous epithelium, and necrosis of esophageal mucosa, with possible involvement of submucosa and muscularis propria, are present. Classification of the disease spectrum is best described by a staging system. Treatment is directed at correcting coexisting clinical conditions, restoring hemodynamic stability, nil-per-os restriction, supportive red blood cell transfusion, and intravenous acid suppression with proton pump inhibitors. Complications include perforation with mediastinal infection/abscess, esophageal stricture and stenosis, superinfection, and death. A high mortality of 32% seen in the setting of AEN syndrome is usually related to the underlying medical co

[Complete necrosis of the penis and testes by strangulation in a psychotic patient].

PubMed

Bart, S; Culty, T; Pizzoferrato, A-C; Thibault, F; Girault, N; Chartier-Kastler, E; Richard, F

2008-07-01

Complete necrosis of the penis and scrotum due to strangulation of the external genitalia is unusually encountered in urologic emergencies. Urological conservative management is recommended. Delayed presentation is a major source of complications. We report the case of a psychotic patient, who was transferred from the emergency department in a context of complete necrosis of the external genitalia. This patient's history included chronic psychotic disorder and positive HIV serology, but he refused to take either neuroleptic or antiretroviral therapy. Complete amputation of the penis and bilateral orchidectomy were performed. We report the first six months of medical management.

Topical application of nitrosonifedipine, a novel radical scavenger, ameliorates ischemic skin flap necrosis in a mouse model.

PubMed

Fukunaga, Yutaka; Izawa-Ishizawa, Yuki; Horinouchi, Yuya; Sairyo, Eriko; Ikeda, Yasumasa; Ishizawa, Keisuke; Tsuchiya, Koichiro; Abe, Yoshiro; Hashimoto, Ichiro; Tamaki, Toshiaki

2017-04-01

Ischemic skin flap necrosis can occur in random pattern flaps. An excess amount of reactive oxygen species is generated and causes necrosis in the ischemic tissue. Nitrosonifedipine (NO-NIF) has been demonstrated to possess potent radical scavenging ability. However, there has been no study on the effects of NO-NIF on ischemic skin flap necrosis. Therefore, they evaluated the potential of NO-NIF in ameliorating ischemic skin flap necrosis in a mouse model. A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of C57BL/6 mice. NO-NIF was administered by topical injection immediately after surgery and every 24 hours thereafter. Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested on postoperative days 1 and 3 to analyze oxidative stress, apoptosis and endothelial dysfunction. The viable area of the flap in the NO-NIF group was significantly increased (78.30 ± 7.041%) compared with that of the control group (47.77 ± 6.549%, p < 0.01). NO-NIF reduced oxidative stress, apoptosis and endothelial dysfunction, which were evidenced by the decrease of malondialdehyde, p22phox protein expression, number of apoptotic cells, phosphorylated p38 MAPK protein expression, and vascular cell adhesion molecule-1 protein expression while endothelial nitric oxide synthase protein expression was increased. In conclusion, they demonstrated that NO-NIF ameliorated ischemic skin flap necrosis by reducing oxidative stress, apoptosis, and endothelial dysfunction. NO-NIF is considered to be a candidate for the treatment of ischemic flap necrosis. © 2017 by the Wound Healing Society.

Regulation of necrotic cell death: p53, PARP1 and cyclophilin D-overlapping pathways of regulated necrosis?

PubMed

Ying, Yuan; Padanilam, Babu J

2016-06-01

In contrast to apoptosis and autophagy, necrotic cell death was considered to be a random, passive cell death without definable mediators. However, this dogma has been challenged by recent developments suggesting that necrotic cell death can also be a regulated process. Regulated necrosis includes multiple cell death modalities such as necroptosis, parthanatos, ferroptosis, pyroptosis, and mitochondrial permeability transition pore (MPTP)-mediated necrosis. Several distinctive executive molecules, particularly residing on the mitochondrial inner and outer membrane, amalgamating to form the MPTP have been defined. The c-subunit of the F1F0ATP synthase on the inner membrane and Bax/Bak on the outer membrane are considered to be the long sought components that form the MPTP. Opening of the MPTP results in loss of mitochondrial inner membrane potential, disruption of ATP production, increased ROS production, organelle swelling, mitochondrial dysfunction and consequent necrosis. Cyclophilin D, along with adenine nucleotide translocator and the phosphate carrier are considered to be important regulators involved in the opening of MPTP. Increased production of ROS can further trigger other necrotic pathways mediated through molecules such as PARP1, leading to irreversible cell damage. This review examines the roles of PARP1 and cyclophilin D in necrotic cell death. The hierarchical role of p53 in regulation and integration of key components of signaling pathway to elicit MPTP-mediated necrosis and ferroptosis is explored. In the context of recent insights, the indistinct role of necroptosis signaling in tubular necrosis after ischemic kidney injury is scrutinized. We conclude by discussing the participation of p53, PARP1 and cyclophilin D and their overlapping pathways to elicit MPTP-mediated necrosis and ferroptosis in acute kidney injury.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mirkovic, D; Peeler, C; Grosshans, D

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 tomore » 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.« less

Identification of involved tissue during surgical treatment of doxorubicin-induced extravasation necrosis.

PubMed

Cohen, F J; Manganaro, J; Bezozo, R C

1983-01-01

The extravascular escape of intravenously administered doxorubicin (Adriamycin) leads to a painful, slowly enlarging subcutaneous lesion which, if not diagnosed, will progress to a chronic severe cellulitis with inflammatory reaction, ulceration of the skin, and possible further involvement. Past attempts at immediate treatment have failed because of, or have been complicated by, incomplete removal of the doxorubicin with continuing tissue necrosis. Three patients who underwent antineoplastic therapy with doxorubicin suffered extravasation leading to deep tissue necrosis requiring skin grafts. In all cases identification of doxorubicin-containing tissue was accomplished by injection of fluorescein. The residual necrotic tissue that did not fluoresce was removed. A protocol is presented to detect doxorubicin extravasation and distinguish the viable from the nonviable components.

Intestinal Fatty Acid Binding Protein as a Marker of Necrosis and Severity in Acute Pancreatitis.

PubMed

Kupčinskas, Juozas; Gedgaudas, Rolandas; Hartman, Hannes; Sippola, Tomi; Lindström, Outi; Johnson, Colin D; Regnér, Sara

2018-07-01

The aim of this study was to study intestinal fatty acid binding protein (i-FABP) as a potential biomarker in predicting severity of acute pancreatitis (AP). In a prospective multicenter cohort study, plasma levels of i-FABP were measured in 402 patients with AP. Severity of AP was determined based on the 1992 Atlanta Classification. Admission levels of plasma i-FABP were significantly higher in patients with pancreatic necrosis, in patients having systemic complications, in patients treated invasively, in patients treated in the intensive care unit, in patients with severe AP, and in deceased patients. Plasma i-FABP levels on admission yielded an area under curve (AUC) of 0.732 in discriminating patients with or without pancreatic necrosis and AUC of 0.669 in predicting severe AP. Combination of levels of i-FABP and venous lactate on the day of admission showed higher discriminative power in severe AP-AUC of 0.808. Higher i-FABP levels on admission were associated with pancreatic necrosis, systemic complications, and severe AP. Low levels of i-FABP had a high negative predictive value for pancreatic necrosis and severe AP. Combination of levels of i-FABP and venous lactates on admission were superior to either of markers used alone in predicting severe AP.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, Edward T.

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) hmore » 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.« less

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

Efficacy of tumour necrosis factor antagonists on remission, colectomy and hospitalisations in ulcerative colitis: Meta-analysis of placebo-controlled trials.

PubMed

Lopez, Anthony; Ford, Alexander C; Colombel, Jean-Frédéric; Reinisch, Walter; Sandborn, William J; Peyrin-Biroulet, Laurent

2015-05-01

The potential for disease modification of tumour necrosis factor antagonists in ulcerative colitis remains debated. We searched MEDLINE, the Cochrane Library and EMBASE. Clinical response/remission, mucosal healing, colectomy, disease-related hospitalisations, and adverse events were analysed by the methods of Peto and Der Simonian and Laird. Five trials enrolled 3654 patients (anti-tumour necrosis factor=2338). Anti-tumour necrosis factor therapy was more effective than placebo to induce and maintain clinical remission, with a number needed to treat of 12 (95% confidence interval [CI], 7-35) and 6 (95% CI, 4-12) for adalimumab and infliximab, respectively. Anti-tumour necrosis factor therapy was more effective than placebo to induce and maintain mucosal healing, with number needed to treat of 9 (95% CI, 5-48), 7 (95% CI, 5-17), 4 (95% CI, 3-6) for adalimumab, golimumab and infliximab, respectively. Only infliximab was associated with a reduced need for colectomy. Both infliximab and adalimumab were associated with less hospitalisations. Anti-tumour necrosis factor therapy did not increase the risk of adverse events. Anti-tumour necrosis factor therapy is more effective than placebo to induce and maintain clinical remission and mucosal healing. Both infliximab and adalimumab are associated with less hospitalisations. Infliximab reduces the need for colectomy. Anti-tumour necrosis factor therapy does not increase the risk of adverse events. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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.

Metabolic epidermal necrosis in two dogs with different underlying diseases.

PubMed

Bond, R; McNeil, P E; Evans, H; Srebernik, N

1995-05-06

Two dogs with metabolic epidermal necrosis had hyperkeratosis of the footpads accompanied by erythematous, erosive and crusting lesions affecting the muzzle, external genitalia, perineum and periocular regions. Histopathological examination of skin biopsies revealed a superficial hydropic dermatitis with marked parakeratosis. Both dogs had high plasma activities of alkaline phosphatase and alanine aminotransferase and high concentrations of glucose, and also a marked hypoaminoacidaemia. Despite these similarities, the cutaneous eruptions were associated with different underlying diseases. One dog had a pancreatic carcinoma which had metastasised widely; the primary tumour and the metastases showed glucagon immunoreactivity on immunocytochemical staining, and the dog's plasma glucagon concentration was markedly greater than that of control dogs. The other dog had diffuse hepatic disease; its plasma glucagon concentration was similar to that of control samples and cirrhosis was identified post mortem. Metabolic epidermal necrosis in dogs is a distinct cutaneous reaction pattern which may be associated with different underlying systemic diseases; however, the pathogenesis of the skin lesions remains unclear.

Dose-volume histogram analysis of brainstem necrosis in head and neck tumors treated using carbon-ion radiotherapy.

PubMed

Shirai, Katsuyuki; Fukata, Kyohei; Adachi, Akiko; Saitoh, Jun-Ichi; Musha, Atsushi; Abe, Takanori; Kanai, Tatsuaki; Kobayashi, Daijiro; Shigeta, Yuka; Yokoo, Satoshi; Chikamatsu, Kazuaki; Ohno, Tatsuya; Nakano, Takashi

2017-10-01

We aimed to evaluate the relationship between brainstem necrosis and dose-volume histograms in patients with head and neck tumors after carbon-ion radiotherapy. We evaluated 85 patients with head and neck tumors who underwent carbon-ion radiotherapy and were followed-up for ≥12months. Brainstem necrosis was evaluated using the Common Terminology Criteria for Adverse Events (version 4.0). The median follow-up was 24months, and four patients developed grade 1 brainstem necrosis, with 2-year and 3-year cumulative rates of 2.8% and 6.5%, respectively. Receiver operating characteristic curve analysis revealed the following significant cut-off values: a maximum brainstem dose of 48Gy (relative biological effectiveness [RBE]), D1cm 3 of 27Gy (RBE), V40Gy (RBE) of 0.1cm 3 , V30Gy (RBE) of 0.7cm 3 , and V20Gy (RBE) of 1.4cm 3 . Multivariate analysis revealed that V30Gy (RBE) was most significantly associated with brainstem necrosis. The 2-year cumulative rates were 33% and 0% for V30Gy (RBE) of ≥0.7cm 3 and <0.7cm 3 , respectively (p<0.001). The present study indicated that the dose constraints might help minimize brainstem necrosis after carbon-ion radiotherapy. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Labial necrosis after uterine artery embolization for leiomyomata.

PubMed

Yeagley, Thomas J; Goldberg, Jay; Klein, Thomas A; Bonn, Joseph

2002-11-01

Uterine artery embolization is increasingly used as an alternative to myomectomy, hysterectomy, and medical treatment for the management of symptomatic leiomyomata. A woman with an 18-week-size fibroid uterus who underwent uterine artery embolization developed a 3-cm, exquisitely tender, hypopigmented, necrotic-appearing area on the right labium minus. Spontaneous resolution occurred over 4 weeks. Labial necrosis is a possible complication of uterine artery embolization and may be successfully managed with conservative therapy.

Analysis for apoptosis and necrosis on adipocytes, stromal vascular fraction, and adipose-derived stem cells in human lipoaspirates after liposuction.

PubMed

Wang, Wei Z; Fang, Xin-Hua; Williams, Shelley J; Stephenson, Linda L; Baynosa, Richard C; Wong, Nancy; Khiabani, Kayvan T; Zamboni, William A

2013-01-01

Adipose-derived stem cells have become the most studied adult stem cells. The authors examined the apoptosis and necrosis rates for adipocyte, stromal vascular fraction, and adipose-derived stem cells in fresh human lipoaspirates. Human lipoaspirate (n = 8) was harvested using a standard liposuction technique. Stromal vascular fraction cells were separated from adipocytes and cultured to obtain purified adipose-derived stem cells. A panel of stem cell markers was used to identify the surface phenotypes of cultured adipose-derived stem cells. Three distinct stem cell subpopulations (CD90/CD45, CD105/CD45, and CD34/CD31) were selected from the stromal vascular fraction. Apoptosis and necrosis were determined by annexin V/propidium iodide assay and analyzed by flow cytometry. The cultured adipose-derived stem cells demonstrated long-term proliferation and differentiation evidenced by cell doubling time and positive staining with oil red O and alkaline phosphatase. Isolated from lipoaspirates, adipocytes exhibited 19.7 ± 3.7 percent apoptosis and 1.1 ± 0.3 percent necrosis; stromal vascular fraction cells revealed 22.0 ± 6.3 percent of apoptosis and 11.2 ± 1.9 percent of necrosis; stromal vascular fraction cells had a higher rate of necrosis than adipocytes (p < 0.05). Among the stromal vascular fraction cells, 51.1 ± 3.7 percent expressed CD90/CD45, 7.5 ± 1.0 percent expressed CD105/CD45, and 26.4 ± 3.8 percent expressed CD34/CD31. CD34/CD31 adipose-derived stem cells had lower rates of apoptosis and necrosis compared with CD105/CD45 adipose-derived stem cells (p < 0.05). Adipose-derived stem cells had a higher rate of apoptosis and necrosis than adipocytes. However, the extent of apoptosis and necrosis was significantly different among adipose-derived stem cell subpopulations.

Correlation of tumor response on computed tomography with pathological necrosis in hepatocellular carcinoma treated by chemoembolization before liver transplantation.

PubMed

Dioguardi Burgio, Marco; Ronot, Maxime; Bruno, Onorina; Francoz, Claire; Paradis, Valérie; Castera, Laurent; Durand, François; Soubrane, Olivier; Vilgrain, Valérie

2016-11-01

The purpose of this article was to compare the results of Response Evaluation Criteria in Solid Tumors (RECIST), modified Response Evaluation Criteria in Solid Tumors (mRECIST), and European Association for the Study of the Liver (EASL) criteria for the evaluation of tumor necrosis in patients treated with transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma. Response to treatment was evaluated on computed tomography scan by 2 independent readers based on RECIST, mRECIST, and EASL criteria, and compared with tumor necrosis assessed by explant pathology. Necrosis was defined as major when >90%. Factors associated with major necrosis were tested by multivariate analysis. Fifty-eight patients (53 males; mean age, 54 years; range, 31-64 years) were included with 88 nodules. Fifty-one (58%) nodules were shown to have major necrosis. Among them readers 1 and 2 identified a complete response (CR) according to RECIST, mRECIST, and EASL criteria in 2 (4%), 47 (92%), and 47 (92%), and 1 (2%), 45 (88%), and 45 (88%) nodules, respectively. However, 12-14 of 59 nodules classified as CR on mRECIST or EASL criteria were found to have intermediate or minor necrosis (overestimation in 20%-24% of the patients). Combining the classification of CR by mRECIST and EASL criteria and complete lipiodol deposition reduced the overestimation to 11%. Among 59 nodules classified with a CR according to mRECIST or EASL, those with complete lipiodol deposition (n = 36, 61%) had a higher rate of necrosis than those with incomplete lipiodol deposition (n = 23, 39%): 95% versus 68% and 95% versus 63% for reader 1 and 2, respectively. In conclusion, CR based on mRECIST/EASL combined with complete lipiodol deposition was better for identification of major tumor necrosis. Even in the presence of CR according to mRECIST/EASL, incomplete lipiodol deposition should be considered indicative of substantial viable tumor remnant. Liver Transplantation 22 1491

The role of tumour necrosis factor-α and tumour necrosis factor receptor signalling in inflammation-associated systemic genotoxicity

PubMed Central

Westbrook, Aya M.; Wei, Bo; Hacke, Katrin; Xia, Menghang; Braun, Jonathan; Schiestl, Robert H.

2012-01-01

Chronic inflammatory diseases are characterised by systemically elevated levels of tumour necrosis factor (TNF)-α, a proinflammatory cytokine with pleiotropic downstream effects. We have previously demonstrated increased genotoxicity in peripheral leukocytes and various tissues in models of intestinal inflammation. In the present study, we asked whether TNF-α is sufficient to induce DNA damage systemically, as observed in intestinal inflammation, and whether tumour necrosis factor receptor (TNFR) signalling would be necessary for the resultant genotoxicity. In the wild-type mice, 500 ng per mouse of TNF-α was sufficient to induce DNA damage to multiple cell types and organs 1-h post-administration. Primary splenic T cells manifested TNF-α-induced DNA damage in the absence of other cell types. Furthermore, TNFR1−/−TNFR2−/− mice demonstrated decreased systemic DNA damage in a model of intestinal inflammation and after TNF-α injection versus wild-type mice, indicating the necessity of TNFR signalling. Nuclear factor (NF)-κB inhibitors were also able to decrease damage induced by TNF-α injection in wild-type mice. When TNF-α administration was combined with interleukin (IL)-1β, another proinflammatory cytokine, DNA damage persisted for up to 24 h. When combined with IL-10, an anti-inflammatory cytokine, decreased genotoxicity was observed in vivo and in vitro. TNF-α/TNFR-mediated signalling is therefore sufficient and plays a large role in mediating DNA damage to various cell types, subject to modulation by other cytokines and their mediators. PMID:21980144

A necrosis-inducing elicitor domain encoded by both symptomatic and asymptomatic Plantago asiatica mosaic virus isolates, whose expression is modulated by virus replication.

PubMed

Komatsu, Ken; Hashimoto, Masayoshi; Maejima, Kensaku; Shiraishi, Takuya; Neriya, Yutaro; Miura, Chihiro; Minato, Nami; Okano, Yukari; Sugawara, Kyoko; Yamaji, Yasuyuki; Namba, Shigetou

2011-04-01

Systemic necrosis is the most destructive symptom induced by plant pathogens. We previously identified amino acid 1154, in the polymerase domain (POL) of RNA-dependent RNA polymerase (RdRp) of Plantago asiatica mosaic virus (PlAMV), which affects PlAMV-induced systemic necrosis in Nicotiana benthamiana. By point-mutation analysis, we show that amino acid 1,154 alone is not sufficient for induction of necrotic symptoms. However, PlAMV replicons that can express only RdRp, derived from a necrosis-inducing PlAMV isolate, retain their ability to induce necrosis, and transient expression of PlAMV-encoded proteins indicated that the necrosis-eliciting activity resides in RdRp. Moreover, inducible-overexpression analysis demonstrated that the necrosis was induced in an RdRp dose-dependent manner. In addition, during PlAMV infection, necrotic symptoms are associated with high levels of RdRp accumulation. Surprisingly, necrosis-eliciting activity resides in the helicase domain (HEL), not in the amino acid 1,154-containing POL, of RdRp, and this activity was observed even in HELs of PlAMV isolates of which infection does not cause necrosis. Moreover, HEL-induced necrosis had characteristics similar to those induced by PlAMV infection. Overall, our data suggest that necrotic symptoms induced by PlAMV infection depend on the accumulation of a non-isolate specific elicitor HEL (even from nonnecrosis isolates), whose expression is indirectly regulated by amino acid 1,154 that controls replication.

CCL11-induced eosinophils inhibit the formation of blood vessels and cause tumor necrosis.

PubMed

Xing, Yanjiang; Tian, Yijun; Kurosawa, Takamasa; Matsui, Sayaka; Touma, Maki; Yanai, Takanori; Wu, Qiong; Sugimoto, Kenkichi

2016-06-01

We previously demonstrated that IL-18 and CCL11 were highly expressed in an NFSA tumor cell line that showed limited angiogenesis and severe necrosis. However, IL-18 was not responsible for the immune cell accumulation and necrosis. Here, we attempted to clarify the relevance of CCL11 in angiogenesis and tumor formation. We established CCL11-overexpressing MS-K cell clones (MS-K-CCL11) to assess the role of CCL11 in immune cell accumulation and angiogenesis. The MS-K-CCL11 cells did not form tumors in mice. MS-K-CCL11-conditioned medium (CM) and recombinant CCL11 induced macrophage and eosinophil differentiation from bone marrow cells. The MS-K-CCL11-CM effectively recruited the differentiated eosinophils. Furthermore, the eosinophils damaged the MS-K, NFSA and endothelial cells in a dose-dependent manner. Administration of an antagonist of CCR3, a CCL11 receptor, to NFSA tumor-bearing mice restored the blood vessel formation and blocked the eosinophil infiltration into the NFSA tumors. Furthermore, other CCL11-overexpressing LM8 clones were established, and their tumor formation ability was reduced compared to the parental LM8 cells, accompanied by increased eosinophil infiltration, blockade of angiogenesis and necrosis. These results indicate that CCL11 was responsible for the limited angiogenesis and necrosis by inducing and attracting eosinophils in the tumors. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Phloem Necrosis of American Elm in the Mississippi Delta

Treesearch

T. H. Filer

1966-01-01

Phloem necrosis in elms, caused by the virus Morsus ulmi Holmes, has been found at Rolling Fork, Mississippi, 60 miles northwest of Jackson and 47 miles north of Vicksburg, in the Delta hardwoods area. It was first reported in Mississippi in 1941, when it was found at Jackson, and it appeared in the northeastern part of the State in 1945.

Serratia marcescens Necrotizing Fasciitis Presenting as Bilateral Breast Necrosis

PubMed Central

Rehman, Tayyab; Moore, Thomas A.

2012-01-01

Serratia marcescens is an extremely rare cause of necrotizing fasciitis. We report the first case of necrotizing fasciitis of the chest wall due to infection with S. marcescens that initially manifested as bilateral breast necrosis. The patient had a fulminant course leading to death within 72 h of presentation. Literature pertinent to S. marcescens-mediated necrotizing fasciitis is also reviewed. PMID:22837315

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

Regulation of necrotic cell death p53, PARP1 and Cyclophilin D -overlapping pathways of regulated necrosis?

PubMed Central

Ying, Yuan; Padanilam, Babu J.

2017-01-01

In contrast to apoptosis and autophagy, necrotic cell death was considered to be a random, passive cell death without definable mediators. However, this dogma has been challenged by recent developments suggesting that necrotic cell death can also be a regulated process. Regulated necrosis includes multiple cell death modalities such as necroptosis, parthanatos, ferroptosis, pyroptosis, and mitochondrial permeability transition pore (MPTP)-mediated necrosis. Several distinctive executive molecules, particularly residing on the mitochondrial inner and outer membrane, amalgamating to form the MPTP have been defined. The c-subunit of the F1F0ATP synthase on the inner membrane and Bax/Bak on the outer membrane are considered to be the long sought components that form the MPTP. Opening of the MPTP results in loss of mitochondrial inner membrane potential, disruption of ATP production, increased ROS production, organelle swelling, mitochondrial dysfunction and consequent necrosis. Cyclophilin D, along with adenine nucleotide translocator (ANT) and the phosphate carrier (PiC) are considered to be important regulators involved in the opening of MPTP. Increased production of ROS can further trigger other necrotic pathways mediated through molecules such as PARP1, leading to irreversible cell damage. This review examines the roles of PARP1 and cyclophilin D in necrotic cell death. The hierarchical role of p53 in regulation and integration of key components of signaling pathway to elicit MPTP-mediated necrosis and ferroptosis is explored. In the context of recent insights, the indistinct role of necroptosis signaling in tubular necrosis after ischemic kidney injury is scrutinized. We conclude by discussing the participation of p53, PARP1 and cyclophilin D and their overlapping pathways to elicit MPTP-mediated necrosis and ferroptosis in acute kidney injury. PMID:27048819

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. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

Proactive infectious disease approach to dermatologic patients who are taking tumor necrosis factor-alfa antagonists: Part II. Screening for patients on tumor necrosis factor-alfa antagonists.

PubMed

Chirch, Lisa M; Cataline, Philip R; Dieckhaus, Kevin D; Grant-Kels, Jane M

2014-07-01

Tumor necrosis factor-alfa levels are linked to disease severity in patients with inflammatory conditions, such as psoriasis. Inhibitors of this cytokine are commonly used with significant success in the treatment of such inflammatory disorders. Their use, however, can be plagued by infectious complications. An awareness of potential infections associated with these therapies is critical in order to maximize preventive efforts both before and during therapy. This review provides a guide for dermatologists caring for patients in need of this type of biologic therapy to preemptively address the infectious risks. Part II of this continuing medical education article reviews recommended screening methods for patients undergoing evaluations for tumor necrosis factor inhibitor therapy for psoriasis or other dermatologic diseases, and discusses possible prophylactic strategies to use, including the appropriate use of immunizations. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Cardioprotective Role of Tumor Necrosis Factor Receptor-Associated Factor 2 by Suppressing Apoptosis and Necroptosis.

PubMed

Guo, Xiaoyun; Yin, Haifeng; Li, Lei; Chen, Yi; Li, Jing; Doan, Jessica; Steinmetz, Rachel; Liu, Qinghang

2017-08-22

Programmed cell death, including apoptosis, mitochondria-mediated necrosis, and necroptosis, is critically involved in ischemic cardiac injury, pathological cardiac remodeling, and heart failure progression. Whereas apoptosis and mitochondria-mediated necrosis signaling is well established, the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure remain elusive. We examined the role of tumor necrosis factor receptor-associated factor 2 (Traf2) in regulating myocardial necroptosis and remodeling using genetic mouse models. We also performed molecular and cellular biology studies to elucidate the mechanisms by which Traf2 regulates necroptosis signaling. We identified a critical role for Traf2 in myocardial survival and homeostasis by suppressing necroptosis. Cardiac-specific deletion of Traf2 in mice triggered necroptotic cardiac cell death, pathological remodeling, and heart failure. Plasma tumor necrosis factor α level was significantly elevated in Traf2 -deficient mice, and genetic ablation of TNFR1 largely abrogated pathological cardiac remodeling and dysfunction associated with Traf2 deletion. Mechanistically, Traf2 critically regulates receptor-interacting proteins 1 and 3 and mixed lineage kinase domain-like protein necroptotic signaling with the adaptor protein tumor necrosis factor receptor-associated protein with death domain as an upstream regulator and transforming growth factor β-activated kinase 1 as a downstream effector. It is important to note that genetic deletion of RIP3 largely rescued the cardiac phenotype triggered by Traf2 deletion, validating a critical role of necroptosis in regulating pathological remodeling and heart failure propensity. These results identify an important Traf2-mediated, NFκB-independent, prosurvival pathway in the heart by suppressing necroptotic signaling, which may serve as a new therapeutic target for pathological remodeling and heart failure. © 2017 American Heart

Validation of preclinical multiparametric imaging for prediction of necrosis in hepatocellular carcinoma after embolization.

PubMed

Braren, Rickmer; Altomonte, Jennifer; Settles, Marcus; Neff, Frauke; Esposito, Irene; Ebert, Oliver; Schwaiger, Markus; Rummeny, Ernst; Steingoetter, Andreas

2011-11-01

The hepatocellular carcinoma (HCC) exhibits varying degrees of vascularization with more poorly differentiated carcinoma commonly exhibiting high amounts of vascularization. Transcatheter arterial embolization (TAE) of HCC tumor nodules results in varying amounts of tumor necrosis. Reliable quantification of necrosis after TAE, would aid in treatment planning and testing of novel combinatorial treatment regimen. The aim of this work was to validate different imaging parameters as individual or combined predictors of tumor necrosis after TAE in an orthotopic rat HCC tumor model. Unifocal rat HCC was imaged by T(2)-weighted MRI, quantitative dynamic contrast enhanced (DCE) MRI, diffusion weighted MRI (DWI) and [(18)F]-FDG PET imaging before (day-1) and after (days 1 and 3) TAE. Univariate and multivariate regression analyses were carried out to analyze the ability of each imaging parameter to predict the percent residual vital tumor (vtu) and vital tissue (vti) as determined by quantitative histopathology. TAE induced a wide range of tumor necrosis. Tumor volume was the only parameter showing a correlation with vti (r(2) = 0.63) before TAE. After TAE, moderate correlations were found for FDG tracer uptake (r(2) = 0.56) and plasma tissue transfer constant (r(2) = 0.55). Correlations were higher for the extravascular extracellular volume fraction (v(e), r(2) = 0.68) and highest for the apparent diffusion coefficient (ADC, r(2) = 0.86). Multivariate analyses confirmed highest correlation of ADC and v(e) with vtu and vti. DWI and DCE-MRI with the respective parameters ADC (day 3) and v(e) (day 1) were identified as the most promising imaging techniques for the prediction of necrosis. This study validates a preclinical platform allowing for the improved tumor stratification after TAE and thus the testing of novel combinatorial therapy approaches in HCC. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Sudden death associated with myocardial contraction band necrosis in Boer goat kids.

PubMed

Amini, K; Simko, E; Davies, J L

2011-11-01

Parenteral selenium (Se) and vitamin E (Vit E) were administered to all newborn kids at a Boer goat farm where there was previous high neonatal mortality assumed to be due to nutritional myopathy. All treated kids were affected by severe respiratory distress and died within 8 hours of Se/Vit E administration. Gross lesions included severe pulmonary edema, hydrothorax, and hydropericardium. The primary histopathologic finding was severe, acute, and monophasic myocardial contraction band necrosis. The diagnosis was accidental acute selenosis based on trace mineral analysis of the liver. This case highlights an important differential diagnosis in cases of acute myocardial contraction band necrosis and sudden death in goats and emphasizes the need for caution when administering parenteral Se/Vit E preparations.

Prognostic role of tumor necrosis in patients undergoing curative resection for gastric gastrointestinal stromal tumor: a multicenter analysis of 740 cases in China.

PubMed

Liu, Xuechao; Qiu, Haibo; Zhang, Peng; Feng, Xingyu; Chen, Tao; Li, Yong; Tao, Kaixiong; Li, Guoxin; Sun, Xiaowei; Zhou, Zhiwei

2017-12-01

Tumor necrosis is associated with poor clinical outcomes in many malignancies. We aimed to determine whether tumor necrosis was an independent predictor of outcomes in gastric gastrointestinal stromal tumors (GISTs). We retrospectively analyzed data from 740 patients undergoing curative resection for gastric GIST at four centers between 2001 and 2015. Disease-free survival (DFS) was estimated with the Kaplan-Meier method, and associations with prognosis were assessed with Cox regression models. Tumor necrosis was present in 122 cases (16.5%). The prevalence of tumor necrosis increased with higher risk-stratification, including 0.7%, 7.4%, 17.3%, and 39.3% for very low-, low-, intermediate- and high-risk tumors, respectively (P < 0.001). Tumor necrosis was associated with aggressive tumor biology, such as larger tumor size, higher mitotic index, tumor rupture, and presence of nuclear atypia (all P < 0.05). Multivariate analysis revealed that tumor necrosis was an independent predictor of unfavorable DFS (HR: 2.641; 95% CI: 1.359-5.131; P = 0.004). When stratified by the modified National Institutes of Health (NIH) classification, tumor necrosis still independently predicted DFS in high-risk patients (P = 0.001) but not in non-high-risk patients (P = 0.349). The 5-year DFS rate in high-risk patients with and without tumor necrosis was 56.5% and 82.9%, respectively (P = 0.004). Notably, the prognostic significance of tumor necrosis was maintained when the patients were stratified by age, sex, tumor location, tumor size, and mitotic index (All P < 0.05). Tumor necrosis is a useful predictor of outcomes in gastric GIST, especially in high-risk patients. Based on these results, we recommend that the current NIH classification should be further improved and expanded to include tumor necrosis as a valuable prognostic indicator. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Fat Necrosis After Partial-Breast Irradiation With Brachytherapy or Electron Irradiation Versus Standard Whole-Breast Radiotherapy-4-Year Results of a Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loevey, Katalin; Fodor, Janos; Major, Tibor

Purpose: To examine the incidence and clinical relevance of fat necrosis after accelerated partial-breast irradiation (PBI) using interstitial high-dose-rate brachytherapy (HDR-BT) in comparison with partial-breast electron irradiation (ELE) and whole-breast irradiation (WBI). Methods and Materials: Between 1998 and 2004, 258 early-stage breast cancer patients were randomized to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 x 5.2 Gy HDR-BT (n = 88) or 50 Gy ELE (n = 40). The incidence of fat necrosis, its impact on cosmetic outcome, accompanying radiologic features, and clinical symptoms were evaluated. Results: The 4-yearmore » actuarial rate of fat necrosis was 31.1% for all patients, and 31.9%, 36.5%, and 17.7% after WBI, HDR-BT and ELE, respectively (p{sub WBI/HDR-BT} = 0.26; p{sub WBI/ELE} = 0.11; p{sub ELE/HDR-BT} = 0.025). The respective rate of asymptomatic fat necrosis was 20.2%, 25.3%, and 10% of patients. The incidence of symptomatic fat necrosis was not significantly different after WBI (8.5%), HDR-BT (11.4%), and ELE (7.5%). Symptomatic fat necrosis was significantly associated with a worse cosmetic outcome, whereas asymptomatic fat necrosis was not. Fat necrosis was detectable with mammography and/or ultrasound in each case. Additional imaging examinations were required in 21% of cases and aspiration cytology in 42%. Conclusions: Asymptomatic fat necrosis is a common adverse event of breast-conserving therapy, having no significant clinical relevance in the majority of the cases. The incidence of both symptomatic and asymptomatic fat necrosis is similar after conventional WBI and accelerated partial-breast HDR-BT.« less

The chevron osteotomy and avascular necrosis.

PubMed

Rothwell, Matthew; Pickard, James

2013-03-01

Avascular necrosis (AVN) of the first metatarsal head following the chevron procedure for hallux valgus correction, has been reported widely in the literature; however, in practice it is rarely encountered and may be an over reported myth associated with the chevron technique. Although an infrequent complication, the consequences for those who develop post-operative AVN can be severe. This paper presents an overview of the pathogenesis and classification of AVN. It reviews the vascular anatomy of the first metatarsal with reference to the surgical technique of chevron osteotomy with lateral release. Imaging techniques are described and the management of AVN and revision surgery are also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Serum tumour necrosis factor alpha in osteopenic and osteoporotic postmenopausal females: A cross-sectional study in Pakistan.

PubMed

Murad, Rafat; Shezad, Zahra; Ahmed, Saara; Ashraf, Mussarat; Qadir, Murad; Rehman, Rehana

2018-03-01

To compare biochemical parameters serum tumour necrosis factor alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D in postmenopausal women. This cross-sectional study was carried out from June 2015 to July 2016 at Jinnah Medical and Dental College, Karachi, and comprised postmenopausal women. Bone mineral density done by dual energy X-ray absorptiometryscan categorised subjects by World Health Organisation classification into normal (T score > -1) osteopenic (T score between -1 and -2.5) and osteoporotic (T score < -2.5). Biochemical parameters like tumour necrosis alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D were measured by solid phase enzyme amplified sensitivity immunoassay method. SPSS 16 was used to analyse the data. Of the 146 women, 34(23%) were normal, 93(67%) were osteopenic and 19(13%) were osteoporotic. There was significant difference in mean body mass index, serum tumour necrosis factor alpha and calcium in all the three groups (p<0.01). Significant mean difference was observed in serum calcium levels between normal and osteopenic, and between normal and osteoporotic group (p<0.05 each) without any significant mean difference between osteopenic and osteoporotic groups (p>0.05). A significant difference was observed for mean tumour necrosis factor alpha values between normal and osteoporotic groups (p<0.05). Tumour necrosis factor alpha showed negative correlation with bone mineral density in osteopenic and osteoporotic groups (p>0.05). Increased bone turnover in postmenopausal osteopenic women can be predicted by increased serum cytokine.

Evaluation of the effects of implant materials and designs on thermal necrosis of bone in cemented hip arthroplasty.

PubMed

Li, Chaodi; Kotha, Shiva; Mason, James

2003-01-01

The exothermic polymerization of bone cement may induce thermal necrosis of bone in cemented hip arthroplasty. A finite element formulation was developed to predict the evolution of the temperature with time in the cemented hip replacement system. The developed method is capable of taking into account both the chemical reaction that generates heat during bone cement polymerization (through a kinetic model) and the physical process of heat conduction (with an energy balance equation). The possibility of thermal necrosis of bone was then evaluated based on the temperature history in the bone and an appropriate damage criterion. Specifically, we evaluate the role of implant materials and designs on the thermal response of the system. Results indicated that the peak temperature at the bone/cement interface with a metal prosthesis was lower than that with a polymer or a composite prosthesis in hip replacement systems. Necrosis of bone was predicted to occur with a polymer or a composite prosthesis while no necrosis was predicted with a metal prosthesis in the simulated conditions. When reinforcing osteoporotic hips with injected bone cement in the cancellous core of the femur, the volume of bone cement implanted is increased which may increase the risk of thermal necrosis of bone. We evaluate whether this risk can be decreased through the use of an insulator to contain the bone cement. No thermal necrosis of bone was predicted with a 3 mm thick polyurethane insulator while more damage is predicted for the use of bone cement without the insulator. This method provides a numerical tool for the quantitative simulation of the thermal behavior of bone-cement-prosthesis designs and for examining and refining new designs computationally.

Change in nomenclature for the immunologic synapse from Troxis Necrosis to trogocytosis.

PubMed

French, Samuel W

2017-10-01

The immunologic synapse mechanism of liver necrosis was termed Troxis Necrosis meaning "nibbling". (Wang MX et al. and French SW. Exp Mol Pathol 2001, 71: 137-146). This mechanism of liver injury was first named "Piecemeal Necrosis" by Hans Popper. It is involved in autoimmune hepatitis, HCV, HBV, primary biliary cirrhosis and steatohepatitis. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the hepatocytic plasma membrane which quickly leads to the removal of the complex from the liver and uptake by the CD4 lymphocyte. This process is performed by the immunologic synapse now called trogocytosis meaning "gnaw" (Martinez-Martin N et al., Immunity 2011, 35: 208-222 and Dustin ML, Cancer Immunol Res 2014, 2: 1023-1033). The repeated episodes of uptake of the hepatocyte bite by bite causes the hepatocyte to slowly disappear like the Cheshire cat. This immunological synapse process is also involved in drug hepatitis, Hashimoto's thyroiditis, type I diabetes, autoimmune adrenalitis, autoimmune gastritis and cancer therapy. Treatment of Alzheimer's disease is also now being studied with PD-L1 antibody as used in the treatment of cancer allowing recruitment of disease modifying leukocytes to the sites of brain pathology (Schwartz M. Science 2017, 357: 254-255). Acknowledgement: Supported by a Grant from NIAAAUO1-021898. Copyright © 2017. Published by Elsevier Inc.

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. Copyright © 2015 by the American Society of Nephrology.

Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production

PubMed Central

Fortes, Guilherme B.; Alves, Leticia S.; de Oliveira, Rosane; Dutra, Fabianno F.; Rodrigues, Danielle; Fernandez, Patricia L.; Souto-Padron, Thais; De Rosa, María José; Kelliher, Michelle; Golenbock, Douglas; Chan, Francis K. M.

2012-01-01

Diseases that cause hemolysis or myonecrosis lead to the leakage of large amounts of heme proteins. Free heme has proinflammatory and cytotoxic effects. Heme induces TLR4-dependent production of tumor necrosis factor (TNF), whereas heme cytotoxicity has been attributed to its ability to intercalate into cell membranes and cause oxidative stress. We show that heme caused early macrophage death characterized by the loss of plasma membrane integrity and morphologic features resembling necrosis. Heme-induced cell death required TNFR1 and TLR4/MyD88-dependent TNF production. Addition of TNF to Tlr4−/− or to Myd88−/− macrophages restored heme-induced cell death. The use of necrostatin-1, a selective inhibitor of receptor-interacting protein 1 (RIP1, also known as RIPK1), or cells deficient in Rip1 or Rip3 revealed a critical role for RIP proteins in heme-induced cell death. Serum, antioxidants, iron chelation, or inhibition of c-Jun N-terminal kinase (JNK) ameliorated heme-induced oxidative burst and blocked macrophage cell death. Macrophages from heme oxygenase-1 deficient mice (Hmox1−/−) had increased oxidative stress and were more sensitive to heme. Taken together, these results revealed that heme induces macrophage necrosis through 2 synergistic mechanisms: TLR4/Myd88-dependent expression of TNF and TLR4-independent generation of ROS. PMID:22262768

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.

Protein A from orange-spotted nervous necrosis virus triggers type I interferon production in fish cell.

PubMed

Huang, Runqing; Zhou, Qiong; Shi, Yan; Zhang, Jing; He, Jianguo; Xie, Junfeng

2018-05-04

Family Nodaviridae consists of two genera: Alphanodavirus and Betanodavirus, and the latter is classified into four genotypes, including red-spotted grouper nervous necrosis virus, tiger puffer nervous necrosis virus, striped jack nervous necrosis virus, and barfin flounder nervous necrosis virus. Type I interferons (IFNs) play a central role in the innate immune system and antiviral responses, and the interactions between IFN and NNV have been investigated in this study. We have found that the RNA-dependent RNA polymerase (RdRp) from orange-spotted nervous necrosis virus (OGNNV), named protein A, was capable of activating IFN promoter in fathead minnow (FHM) cells. Transient expression of protein A was found to induce IFN expression and secretion, endowing FHM cells with anti-tiger frog virus ability. Protein A from SJNNV can also induce IFN expression in FHM cells but that from Flock House virus (FHV), a well-studied representative species of genus Alphanodavirus, cannot. RdRp activity and mitochondrial localization were shown to be required for protein A to induce IFN expression by means of activating IRF3 but not NFκB. Furthermore, DsRNA synthesized in vitro transcription and poly I:C activated IFN promoter activity when transfected into FHM cells, and dsRNA were also detected in NNV-infected cells. We postulated that dsRNA, a PAMP, was produced by protein A, leading to activation of innate immune response. These results suggest that protein As from NNV are the agonists of innate immune response. This is the first work to demonstrate the interaction between NNV protein A and innate immune system, and may help to understand pathogenesis of NNV. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of nitroglycerin ointment on mastectomy flap necrosis in immediate breast reconstruction: a randomized controlled trial.

PubMed

Gdalevitch, Perry; Van Laeken, Nancy; Bahng, Seokjae; Ho, Adelyn; Bovill, Esta; Lennox, Peter; Brasher, Penelope; Macadam, Sheina

2015-06-01

Mastectomy flap necrosis is a common complication of immediate breast reconstruction that impacts recovery time and reconstructive success. Nitroglycerin ointment is a topical vasodilator that has been shown to improve skin flap survival in an animal model. The objective of this study was to evaluate whether the application of nitroglycerin ointment to the breast skin after mastectomy and immediate reconstruction causes a decrease in the rate of mastectomy flap necrosis compared with placebo. This study was conducted as a randomized controlled trial and included patients aged 21 to 69 years undergoing mastectomy and immediate breast reconstruction at the University of British Columbia-affiliated hospitals (Vancouver, British Columbia, Canada). Patients with a medical history that precluded the administration of nitroglycerin were excluded from the study. The target sample size was 400 patients. Nitroglycerin ointment (45 mg) or a placebo was applied to the mastectomy skin at the time of surgical dressing. The trial was stopped at the first interim analysis after 165 patients had been randomized (85 to the treatment group and 80 to the placebo group). Mastectomy flap necrosis developed in 27 patients (33.8 percent) receiving placebo and in 13 patients (15.3 percent) receiving nitroglycerin ointment; the between-group difference was 18.5 percent (p = 0.006; 95 percent CI, 5.3 to 31.0 percent). Postoperative complications were similar in both groups [nitroglycerin, 22.4 percent (19 of 85); placebo, 28.8 percent (23 of 80)]. In patients undergoing mastectomy and immediate reconstruction, there was a marked reduction in mastectomy flap necrosis in patients who received nitroglycerin ointment. Nitroglycerin ointment application is a simple, safe, and effective way to help prevent mastectomy flap necrosis. Therapeutic, I.

Kinetics of tumor necrosis factor production by photodynamic-therapy-activated macrophages

NASA Astrophysics Data System (ADS)

Pass, Harvey I.; Evans, Steven; Perry, Roger; Matthews, Wilbert

1990-07-01

The ability of photodynamic therapy (PDT) to activate macrophages and produce cytokines, specifically tumor necrosis factor (TNF), is unknown. Three day thioglycolate elicited macrophages were incubated with 25 ug/mi Photofrin II (P11) for 2 hour, after which they were subjected to 630 nm light with fluences of 0-1800 J/m. The amount of TNF produced in the system as well as macrophage viability was measured 1, 3, 6, and 18 hours after POT. The level of TNF produced by the macrophages was significantly elevated over control levels 6 hours after POT and the absolute level of tumor necrosis factor production was influenced by the treatment energy and the resulting macrophage cytotoxicity. These data suggest that POT therapy induced cytotoxicity in vivo may be amplified by macrophage stimulation to secrete cytokines and these cytokines may also participate in other direct/indirect photodynamic therapy effects, i.e. immunosuppression, vascular effects.

Predicting Chemically Induced Duodenal Ulcer and Adrenal Necrosis with Classification Trees

NASA Astrophysics Data System (ADS)

Giampaolo, Casimiro; Gray, Andrew T.; Olshen, Richard A.; Szabo, Sandor

1991-07-01

Binary tree-structured statistical classification algorithms and properties of 56 model alkyl nucleophiles were brought to bear on two problems of experimental pharmacology and toxicology. Each rat of a learning sample of 745 was administered one compound and autopsied to determine the presence of duodenal ulcer or adrenal hemorrhagic necrosis. The cited statistical classification schemes were then applied to these outcomes and 67 features of the compounds to ascertain those characteristics that are associated with biologic activity. For predicting duodenal ulceration, dipole moment, melting point, and solubility in octanol are particularly important, while for predicting adrenal necrosis, important features include the number of sulfhydryl groups and double bonds. These methods may constitute inexpensive but powerful ways to screen untested compounds for possible organ-specific toxicity. Mechanisms for the etiology and pathogenesis of the duodenal and adrenal lesions are suggested, as are additional avenues for drug design.

Heparanase procoagulant activity as a predictor of wound necrosis following diabetic foot amputation.

PubMed

Peled, Eli; Melamed, Eyal; Portal, Tali Banker; Axelman, Elena; Norman, Doron; Brenner, Benjamin; Nadir, Yona

2016-03-01

Trans-metatarsal operation to diabetic foot necrosis is a common procedure although only half of the patients do not need a second amputation due to surgery wound ischemia. No current tools are available for early prediction of surgery success and the clinical decision for a second operation may take weeks. Heparanase protein is involved in inflammation, angiogenesis and coagulation activation. The aim of the study was to evaluate heparanase level and procoagulant activity as an early predictor for success or failure of diabetic foot trans-metatarsal surgery. The study group included 40 patients with diabetic foot necrosis requiring trans-metatarsal surgical intervention. Eighteen patients designated as necrotic group, developed post-surgery necrosis at the surgery wound within the first month, requiring a second more proximal amputation. Skin biopsies from the proximal surgery edge were stained for heparanase, tissue factor (TF), TF pathway inhibitor (TFPI) and by hematoxylin and eosin. Plasma samples were drawn pre-surgery and at 1h, 1week and 1month post-surgery. Samples were tested for heparanase levels by ELISA and TF+heparanase activity, TF activity and heparanase procoagulant activity. Skin biopsy staining did not predict subsequent necrosis. In the non-necrotic group a significant rise in TF+heparanase activity, heparanase activity and heparanase levels were observed 1h and 1week post-surgery. The most significant increase was in heparanase procoagulant activity at the time point of 1h post-surgery (P<0.0001). Pre-surgery TF activity was significantly lower in the non-necrotic group compared to the necrotic group (P<0.05). Measuring heparanase procoagulant activity pre-surgery and 1h post-surgery could potentially serve as an early tool to predict the procedure success. The present results broaden our understanding regarding early involvement of heparanase in the wound healing process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rhabdomyolysis with acute tubular necrosis following occupational inhalation of thinners.

PubMed

Ngajilo, D; Ehrlich, R

2017-07-01

Thinners are mixtures of organic solvents commonly containing toluene, xylene, acetone, hexane, benzene and methyl isobutyl ketone. This report describes a case of rhabdomyolysis with acute tubular necrosis and renal failure, most likely attributable to toluene, following occupational exposure to thinners while cleaning a steel water tank. These adverse health effects have previously been reported following acute poisoning or intentional inhalation by drug abusers, but rarely in the occupational setting. Poor working conditions, lack of health and safety training and delayed treatment contributed to the onset and severity of the patient's complications. This case emphasizes the need for strict control measures, including adequate ventilation, training on working in confined spaces, appropriate personal protective equipment and emergency rescue procedures in such settings. In addition, rhabdomyolysis, acute tubular necrosis and renal failure should be added to safety data material as possible complications of excessive inhalation of thinners. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Delayed-onset heparin-induced skin necrosis: a rare complication of perioperative heparin therapy.

PubMed

Gan, Weh Kiat

2017-11-03

An uncommon case of delayed-onset dalteparin-induced skin necrosis in an 83-year-old Caucasian female patient associated with heparin-induced thrombocytopaenia (HIT) presenting on day 30 following dalteparin therapy is reported. Investigations revealed mild thrombocytopaenia with normal protein C, protein S, coagulation screen and positive test for heparin-platelet factor-4 antibody. Clinical diagnosis of heparin-induced skin necrosis with HIT was made. Dalteparin injection was discontinued promptly and substituted with fondaparinux therapy. The patient achieved good recovery following cessation of dalteparin therapy and was subsequently discharged. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Necrosis avid near infrared fluorescent cyanines for imaging cell death and their use to monitor therapeutic efficacy in mouse tumor models

PubMed Central

Xie, Bangwen; Stammes, Marieke A.; van Driel, Pieter B.A.A.; Cruz, Luis J.; Knol-Blankevoort, Vicky T.; Löwik, Martijn A.M.; Mezzanotte, Laura; Que, Ivo; Chan, Alan; van den Wijngaard, Jeroen P.H.M.; Siebes, Maria; Gottschalk, Sven; Razansky, Daniel; Ntziachristos, Vasilis; Keereweer, Stijn; Horobin, Richard W.; Hoehn, Mathias; Kaijzel, Eric L.; van Beek, Ermond R.; Snoeks, Thomas J.A.; Löwik, Clemens W.G.M.

2015-01-01

Quantification of tumor necrosis in cancer patients is of diagnostic value as the amount of necrosis is correlated with disease prognosis and it could also be used to predict early efficacy of anti-cancer treatments. In the present study, we identified two near infrared fluorescent (NIRF) carboxylated cyanines, HQ5 and IRDye 800CW (800CW), which possess strong necrosis avidity. In vitro studies showed that both dyes selectively bind to cytoplasmic proteins of dead cells that have lost membrane integrity. Affinity for cytoplasmic proteins was confirmed using quantitative structure activity relations modeling. In vivo results, using NIRF and optoacoustic imaging, confirmed the necrosis avid properties of HQ5 and 800CW in a mouse 4T1 breast cancer tumor model of spontaneous necrosis. Finally, in a mouse EL4 lymphoma tumor model, already 24 h post chemotherapy, a significant increase in 800CW fluorescence intensity was observed in treated compared to untreated tumors. In conclusion, we show, for the first time, that the NIRF carboxylated cyanines HQ5 and 800CW possess strong necrosis avid properties in vitro and in vivo. When translated to the clinic, these dyes may be used for diagnostic or prognostic purposes and for monitoring in vivo tumor response early after the start of treatment. PMID:26472022

Proteomic changes in plasma of broiler chickens with femoral head necrosis

USDA-ARS?s Scientific Manuscript database

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...

Tumor necrosis and clinical outcomes following neoadjuvant therapy in soft tissue sarcoma: A systematic review and meta-analysis.

PubMed

Salah, Samer; Lewin, Jeremy; Amir, Eitan; Abdul Razak, Albiruni

2018-05-19

The prognostic role of tumor necrosis following neoadjuvant therapy is established in bone sarcomas but remains unclear in soft tissue sarcomas (STS). We searched MEDLINE, MEDLINE in progress, EMBASE and Cochrane to identify studies that investigated neoadjuvant therapy in STS. Studies were required to report survival data based on extent of necrosis, or provided individual patient data allowing estimation thereof. Hazard ratios (HR) for relapse-free (RFS) and overall survival (OS) and odds ratios (OR) for recurrence at 3 years and for death at 5 years were pooled in a random effect meta-analysis. Associations between patient characteristics and attainment of ≥90% necrosis were explored. 21 studies comprising 1663 patients were included. Extremity tumors were most common (n = 1554; 93%). Induction regimens included chemotherapy with radiotherapy (n = 924; 56%), chemotherapy alone (n = 412; 25%), radiotherapy alone (n = 78; 5%), isolated limb perfusion (ILP) (n = 231; 14%), and targeted therapy/radiotherapy (n = 18; 1%). Patients with <90% necrosis had higher hazard of recurrence (hazard ratio [HR] 1.47; 95% CI: 1.06-2.04; p = 0.02) and death (HR 1.86; 95% CI: 1.41-2.46; p < 0.001). Risk of recurrence at 3 years (OR = 3.35; 95% CI: 2.27-4.92; p < 0.001) and of death at 5 years (OR 2.60; 95% CI: 1.59-4.26; p < 0.001) were similarly increased. Compared to other modalities, ILP was associated with higher odds of achieving ≥90% necrosis (OR 12.1; 95% CI: 3.69-39.88; p < 0.001). Tumour necrosis <90% following neoadjuvant therapy is associated with increased recurrence risk and inferior OS in patients with STS. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Antibiotic Injections Control Elm Phloem Necrosis in the Urban Ecosystem

Treesearch

T. H. Filer

1976-01-01

When nine American and cedar elms showing symptoms of elm phloem necrosis were given repeated injections of tetracycline antibiotics for several years, all treated trees recovered and appeared healthy by 1976. All but one of the untreated checks died. Of 10 severely infected American elms treated only during the summer of 1972, seven died and the other three showed...

CYLD Deubiquitinates RIP1 in the TNFα-Induced Necrosome to Facilitate Kinase Activation and Programmed Necrosis

PubMed Central

Moquin, David M.; McQuade, Thomas; Chan, Francis Ka-Ming

2013-01-01

Background Necroptosis/programmed necrosis is initiated by a macro-molecular protein complex termed the necrosome. Receptor interacting protein kinase 1 (RIPK1/RIP1) and RIP3 are key components of the necrosome. TNFα is a prototypic inducer of necrosome activation, and it is widely believed that deubiquitination of RIP1 at the TNFR-1 signaling complex precedes transition of RIP1 into the cytosol where it forms the RIP1-RIP3 necrosome. Cylindromatosis (CYLD) is believed to promote programmed necrosis by facilitating RIP1 deubiquitination at this membrane receptor complex. Methodology/Principal Findings We demonstrate that RIP1 is indeed the primary target of CYLD in TNFα-induced programmed necrosis. We observed that CYLD does not regulate RIP1 ubiquitination at the TNF receptor. TNF and zVAD-induced programmed necrosis was highly attenuated in CYLD-/- cells. However, in the presence of cycloheximide or SMAC mimetics, programmed necrosis was only moderately reduced in CYLD-/- cells. Under the latter conditions, RIP1-RIP3 necrosome formation is only delayed, but not abolished in CYLD-/- cells. We further demonstrate that RIP1 within the NP-40 insoluble necrosome is ubiquitinated and that CYLD regulates RIP1 ubiquitination in this compartment. Hence, RIP1 ubiquitination in this late-forming complex is greatly increased in CYLD-/- cells. Increased RIP1 ubiquitination impairs RIP1 and RIP3 phosphorylation, a signature of kinase activation. Conclusions/Significance Our results show that CYLD regulates RIP1 ubiquitination in the TNFα-induced necrosome, but not in the TNFR-1 signaling complex. In cells sensitized to programmed necrosis with SMAC mimetics, CYLD is not essential for necrosome assembly. Since SMAC mimetics induces the loss of the E3 ligases cIAP1 and cIAP2, reduced RIP1 ubiquitination could lead to reduced requirement for CYLD to remove ubiquitin chains from RIP1 in the TNFR-1 complex. As increased RIP1 ubiquitination in the necrosome correlates with

Mastectomy Skin Necrosis After Breast Reconstruction: A Comparative Analysis Between Autologous Reconstruction and Implant-Based Reconstruction.

PubMed

Sue, Gloria R; Lee, Gordon K

2018-05-01

Mastectomy skin necrosis is a significant problem after breast reconstruction. We sought to perform a comparative analysis on this complication between patients undergoing autologous breast reconstruction and patients undergoing 2-stage expander implant breast reconstruction. A retrospective review was performed on consecutive patients undergoing autologous breast reconstruction or 2-stage expander implant breast reconstruction by the senior author from 2006 through 2015. Patient demographic factors including age, body mass index, history of diabetes, history of smoking, and history of radiation to the breast were collected. Our primary outcome measure was mastectomy skin necrosis. Fisher exact test was used for statistical analysis between the 2 patient cohorts. The treatment patterns of mastectomy skin necrosis were then analyzed. We identified 204 patients who underwent autologous breast reconstruction and 293 patients who underwent 2-stage expander implant breast reconstruction. Patients undergoing autologous breast reconstruction were older, heavier, more likely to have diabetes, and more likely to have had prior radiation to the breast compared with patients undergoing implant-based reconstruction. The incidence of mastectomy skin necrosis was 30.4% of patients in the autologous group compared with only 10.6% of patients in the tissue expander group (P < 0.001). The treatment of this complication differed between these 2 patient groups. In general, those with autologous reconstructions were treated with more conservative means. Although 37.1% of patients were treated successfully with local wound care in the autologous group, only 3.2% were treated with local wound care in the tissue expander group (P < 0.001). Less than half (29.0%) of patients in the autologous group were treated with an operative intervention for this complication compared with 41.9% in the implant-based group (P = 0.25). Mastectomy skin necrosis is significantly more likely to occur after

Johnsongrass mosaic virus contributes to maize lethal necrosis in East Africa

USDA-ARS?s Scientific Manuscript database

Maize lethal necrosis (MLN), a severe virus disease of maize, has emerged in East Africa in recent years with devastating effects on production and food security where maize is a staple subsistence crop. In extensive surveys of MLN-symptomatic plants in East Africa, sequences of Johnsongrass mosaic ...

Biological and genetic characterization of new and known necroviruses causing an emerging systemic necrosis disease of corn salad (Valerianella locusta L.) in France.

PubMed

Verdin, Eric; Marais, Armelle; Wipf-Scheibel, Catherine; Faure, Chantal; Pelletier, Brigitte; David, Perrine; Svanella-Dumas, Laurence; Poisblaud, Clement; Lecoq, Herve'; Candresse, Thierry

2018-02-28

An emerging systemic necrosis disease of corn salad was first observed in the Nantes region of France in the late 2000's. Classical virology and high-throughput sequencing approaches demonstrated that the disease is associated with four different necroviruses, tobacco necrosis virus A (TNVA), tobacco necrosis virus D (TNVD), olive mild mosaic virus (OMMV) and a novel recombinant Alphanecrovirus for which the name corn salad necrosis virus (CSNV) is proposed. Satellite tobacco necrosis virus (STNV) was also frequently observed. Koch's postulates were completed for all four agents, each one alone being able to cause systemic necrosis of varying severity in corn salad. OMMV was the most frequently observed virus and causes the most severe symptoms. TNVA was the second, both in terms of prevalence and symptom severity while TNVD and CSNV were only rarely observed and cause the less severe symptoms. The emergence of this systemic disease may have been favoured by the short and repeated cropping cycles used for corn salad, possibly allowing the selection of necrovirus isolates with an improved ability to systemically invade this specialty crop.

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

Overexpression of HO-1 assisted PM2.5-induced apoptosis failure and autophagy-related cell necrosis.

PubMed

Zhou, Wei; Yuan, Xiaoyan; Zhang, Li; Su, Baoting; Tian, Dongdong; Li, Yang; Zhao, Jun; Wang, Yimei; Peng, Shuangqing

2017-11-01

Severe smog/haze events accompanied by extremely high concentrations of airborne fine particulate matter (PM2.5) have emerged frequently in China and the potential health risks have attracted ever-growing attention. During these episodes, a surge in hospital visits for acute respiratory symptoms and respiratory diseases exacerbation has been reported to be associated with acute exposure to high-levels of particulate matters. To investigate cell fate determination and the underlying pathogenic mechanisms during severe haze episodes or smog events, we exposed human lung epithelial cells (BEAS-2B) to PM2.5 (0-400μg/mL) for 24h and found that high doses of PM2.5 caused cell necrosis and autophagy dysfunction, while co-treatment with the autophagy inhibitor 3-MA could partially reduce PM2.5-induced cell necrosis. Exposure to PM2.5 also increased the expression and mitochondrial transposition of heme oxygenase 1 (HO-1), which consequently reduced the release of cytochrome C from mitochondria to cytosol. Knockdown of HO-1 by siRNA attenuated the mitochondrial accumulation of HO-1, reversed HO-1-induced the reduction of cytochrome C release and promoted PM2.5-induced cell apoptosis. In contrast to necrosis, PM2.5-induced autophagy was independent of HO-1. In conclusion, our results demonstrate that acute exposure to high PM2.5 concentrations causes autophagy-related cell necrosis. The decrease in cytochrome C release and apoptosis by upregulation of HO-1 maybe assist PM2.5-induced autophagy-related cell necrosis. Further, this study reveals dual roles for HO-1 in PM2.5-induced cytotoxicity and presents a possible explanation for the onset of acute respiratory symptoms under extreme particulate air pollution. Copyright © 2017. Published by Elsevier Inc.

Steroid Induced Bilateral Avascular Necrosis of Head of Femur in an Adult Male Patient - A Case Report.

PubMed

Jadeja, Dharamvirsinh; Solanki, Vipul; Chavada, Bhavesh; Tripathi, Chandrabhanu

2016-01-01

A 28 year old male patient, known case of pemphigus vulgaris was on dexamethasone pulse therapy. Total 7 pulses were given after that he developed avascular necrosis of head of femur on both sides, which was confirmed by digital X- ray and MRI. Avascular necrosis is a disabling and progressive condition in young patients gradually leads to femoral head collapse and eventual total hip arthroplasty. As per WHO-UMC causality assessment criteria, the association between reaction and drug was possible, Naranjo's score was 7. According to Modified Schumock and Thornton's criteria, this reaction was not preventable. The Modified Hartwig and Siegel's scale showed that the reaction was severe (level 6). Here we present a case where the use of steroid for pemphigus vulgaris resulting in the development of bilateral avascular necrosis of head of femur.

Radiofrequency thermal ablation in canine femur: evaluation of coagulation necrosis reproducibility and MRI-histopathologic correlation.

PubMed

Lee, Jeong Min; Choi, Seong Hong; Park, Hee Seon; Lee, Min Woo; Han, Chang Jin; Choi, Joon-il; Choi, Ja-Young; Hong, Sung Hwan; Han, Joon Koo; Choi, Byung Ihn

2005-09-01

Our purposes were to determine whether a single application of radiofrequency energy to normal bone can create coagulation necrosis reproducibly and to assess the accuracy of MRI at revealing the extent of radiofrequency-induced thermal bone injury. Using a 200-W generator and a 17-gauge cooled-tip electrode, a total of 11 radiofrequency ablations were performed under fluoroscopic guidance in the distal femurs of seven dogs. Radiofrequency was applied in standard monopolar mode at 100 W for 10 min. During radiofrequency ablation, the changes in impedance and currents were recorded. MRI, including unenhanced T1- and T2-weighted images and contrast-enhanced fat-suppressed T1-weighted images, was performed to evaluate ablation regions. Six dogs were killed on day 4 after MRI and one dog on day 7. In all animals, radiofrequency ablation created a well-defined coagulation necrosis and no significant complications were noted. The mean long-axis diameter and the mean short-axis diameter of the coagulation zones produced were 45.9 +/- 5.5 mm and 17.7 +/- 2.7 mm, respectively. At gross examination, thermal ablation regions appeared as a central, light-brown area with a dark-brown peripheral hemorrhagic zone, which was surrounded by a pale-yellow rim. On MRI, the ablated areas showed multilayered zones with signal intensities that differed from normal marrow on unenhanced images and a perfusion defect on contrast-enhanced T1-weighted images. The maximum difference between lesion sizes on MR images, established by measuring macroscopic coagulation necrosis, was 3 mm. The correlation between the diameter of coagulation necrosis and lesion size at MRI was strong, with correlation coefficients ranging from 0.89 for unenhanced T1-weighted images and 0.97 for unenhanced T2-weighted images to 0.98 for contrast-enhanced T1-weighted images (p < 0.05). Radiofrequency ablation created well-defined coagulation necrosis in a reproducible manner, and MRI accurately determined the extent

Cortical laminar necrosis in dengue encephalitis-a case report.

PubMed

Garg, Ravindra Kumar; Rizvi, Imran; Ingole, Rajan; Jain, Amita; Malhotra, Hardeep Singh; Kumar, Neeraj; Batra, Dhruv

2017-04-20

Dengue encephalitis is a rare neurological manifestation of dengue fever. Its clinical presentation is similar to other viral encephalitides and encephalopathy. No single specific finding on magnetic resonance imaging of dengue encephalitis has yet been documented. They are highly variable and atypical. A 15-year boy presented with fever, the headache and altered sensorium of 12-day duration. On neurological examination, his Glasgow Coma Scale score was 10 (E3M4V3). There was no focal neurological deficit. Laboratory evaluation revealed leukopenia and marked thrombocytopenia. Dengue virus IgM antibody was positive both in serum and cerebrospinal fluid. Magnetic resonance imaging of the brain revealed signal changes in bilateral parietooccipital and left frontal regions (left hemisphere more involved than the right hemisphere). There was gyriform enhancement bilateral parietooccipital regions consistent with cortical laminar necrosis. Bilaterally diffuse subcortical white matter was also involved and subtle T2 hyperintensity involving both basal ganglia was noted. Gradient echo sequence revealed presence of hemorrhage in the subcortical white matter. Patient was treated conservatively and received platelet transfusion. Patient became fully conscious after 7 days. In a patient with highly suggestive dengue e\\ephalitis, we describe an unusual magnetic resonance imaging finding. This report is possibly the first instance of cortical laminar necrosis in such a setting.

The NLP toxin family in Phytophthora sojae includes rapidly evolving groups that lack necrosis-inducing activity.

PubMed

Dong, Suomeng; Kong, Guanghui; Qutob, Dinah; Yu, Xiaoli; Tang, Junli; Kang, Jixiong; Dai, Tingting; Wang, Hai; Gijzen, Mark; Wang, Yuanchao

2012-07-01

Necrosis- and ethylene-inducing-like proteins (NLP) are widely distributed in eukaryotic and prokaryotic plant pathogens and are considered to be important virulence factors. We identified, in total, 70 potential Phytophthora sojae NLP genes but 37 were designated as pseudogenes. Sequence alignment of the remaining 33 NLP delineated six groups. Three of these groups include proteins with an intact heptapeptide (Gly-His-Arg-His-Asp-Trp-Glu) motif, which is important for necrosis-inducing activity, whereas the motif is not conserved in the other groups. In total, 19 representative NLP genes were assessed for necrosis-inducing activity by heterologous expression in Nicotiana benthamiana. Surprisingly, only eight genes triggered cell death. The expression of the NLP genes in P. sojae was examined, distinguishing 20 expressed and 13 nonexpressed NLP genes. Real-time reverse-transcriptase polymerase chain reaction results indicate that most NLP are highly expressed during cyst germination and infection stages. Amino acid substitution ratios (Ka/Ks) of 33 NLP sequences from four different P. sojae strains resulted in identification of positive selection sites in a distinct NLP group. Overall, our study indicates that expansion and pseudogenization of the P. sojae NLP family results from an ongoing birth-and-death process, and that varying patterns of expression, necrosis-inducing activity, and positive selection suggest that NLP have diversified in function.

SU-D-16A-07: Photobleaching Predicts Necrosis in Interstitial PDT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, M; Finlay, J; Liu, B

Purpose: Dosimetry for PDT has proven to be a challenge thus far, and for prediction of PDT outcome, a singlet oxygen model based on fundamental photophysical parameters has been developed. Previously, the photobleaching effect of photosensitizers was taken into account in the singlet oxygen explicit dosimetry model; here we report of direct measurements of photobleaching in the same model to assess the conditions under which implicit dosimetry using photobleaching can serve as an intermediate surrogate for PDT damage. Methods: Fluorescence spectra were measured interstitially in sensitized mouse tumors prior to after irradiation via a cylindrical diffuser. Photobleaching was determined bymore » the relative decrease in fluorescence amplitude from the initial pre-treatment measurement. Spectra were analyzed by singular value decomposition to determine the photosensitizer concentration. Different photosensitizers were used to see the effect of photobleaching on PDT outcome and the impact of fluence on photobleaching. The drugs used were BPD (at two drug-light intervals), HPPH, and Photofrin. PDT outcome was determined by tumor necrosis radii measured upon sectioning and staining of treated tumors. Results: Post-PDT photosentizer concentrations were compared to initial pre-PDT photosensitizer concentrations, and the decrease was greater with a higher fluence measured during treatment. Furthermore, photobleaching and necrosis radius were found to be positively correlated. The relationship between photobleaching and necrosis radius is sensitizer-dependent, however the differences among sensitizers can be understood in terms of their respective photophysical parameters. Conclusions: Photobleaching is predictive of PDT outcome, but a comprehensive singlet oxygen model, has the potential to further improve the prediction of PDT outcome and the understanding of implicit dosimetry.« less

Antimicrobial activity of a multispecies probiotic (Ecologic 641) against pathogens isolated from infected pancreatic necrosis.

PubMed

Ridwan, B U; Koning, C J M; Besselink, M G H; Timmerman, H M; Brouwer, E C; Verhoef, J; Gooszen, H G; Akkermans, L M A

2008-01-01

Although probiotic prophylaxis has been suggested to prevent small bowel bacterial overgrowth, bacterial translocation and infection of pancreatic necrosis in severe acute pancreatitis, limited data are available on their antimicrobial activity. Using the well-diffusion method, we studied the antimicrobial properties of a multispecies probiotic product (Ecologic 641) against a collection of pathogens cultured from infected pancreatic necrosis. All individual probiotic strains included in the multispecies preparation were able to inhibit the growth of the pathogens to some extent. However, the combination of the individual strains (i.e. the multispecies preparation) was able to inhibit all pathogenic isolates. Probiotic-free supernatants adjusted to pH 7 were not able to inhibit pathogen growth. Ecologic 641 is capable of inhibiting growth of a wide variety of pathogens isolated from infected pancreatic necrosis. The antimicrobial properties are to a large extent explained by the production of organic acids. Ecologic 641 is currently being used in a Dutch nationwide double-blind, placebo-controlled, randomized multicentre trial in patients with predicted severe acute pancreatitis.

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Septum necrosis following CPAP treatment of preterm infant].

PubMed

Fjaeldstad, Alexander; Cipliene, Rasa; Ramsgaard-Jensen, Trine; Ebbesen, Finne

2014-05-26

This case describes the complications of intensive respiratory support in a preterm infant. During two months of rigorous nasal continuous positive airway pressure (CPAP) therapy with intermittent use of CPAP-mask and -prongs, an ulcer in the nasal mucus membrane developed into septum necrosis. Preterm infants are in high risk of needing long-term respiratory support, why it is important to bear in mind that binasal CPAP-prongs have proved to be more effective than mononasal therapy, and that CPAP-prongs and -mask have different sites of injury.

Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy.

PubMed

Ruben, Jeremy D; Dally, Michael; Bailey, Michael; Smith, Robin; McLean, Catriona A; Fedele, Pasqual

2006-06-01

To investigate radiation necrosis in patients treated for glioma in terms of incidence, outcomes, predictive and prognostic factors. Records were reviewed for 426 patients followed up until death or for at least 3 years. Logistic regression analysis was performed to identify predictive and prognostic factors. Multivariate survival analysis was conducted using Cox proportional hazards regression. Separate analyses were performed for the subset of 352 patients who received a biologically effective dose (BED) > or =85.5 Gy2 (> or =45 Gy/25 fractions) who were at highest risk for radionecrosis. Twenty-one patients developed radionecrosis (4.9%). Actuarial incidence plateaued at 13.3% after 3 years. In the high-risk subset, radiation parameters confirmed as risk factors included total dose (p < 0.001), BED (p < 0.005), neuret (p < 0.001), fraction size (p = 0.028), and the product of total dose and fraction size (p = 0.001). No patient receiving a BED <96 Gy2 developed radionecrosis. Subsequent chemotherapy significantly increased the risk of cerebral necrosis (p = 0.001) even when adjusted for BED (odds ratio [OR], 5.8; 95% confidence interval [CI], 1.6-20.3) or length of follow-up (OR, 5.4; 95% CI, 1.5-19.3). Concurrent use of valproate appeared to delay the onset of necrosis (p = 0.013). The development of radionecrosis did not affect survival (p = 0.09). Cerebral necrosis is unlikely at doses below 50 Gy in 25 fractions. The risk increases significantly with increasing radiation dose, fraction size, and the subsequent administration of chemotherapy.

Apoptotic cells subjected to cold/warming exposure disorganize apoptotic microtubule network and undergo secondary necrosis.

PubMed

Oropesa-Ávila, Manuel; Fernández-Vega, Alejandro; de la Mata, Mario; Garrido-Maraver, Juan; Cotán, David; Paz, Marina Villanueva; Pavón, Ana Delgado; Cordero, Mario D; Alcocer-Gómez, Elizabet; de Lavera, Isabel; Lema, Rafael; Zaderenko, Ana Paula; Sánchez-Alcázar, José A

2014-09-01

Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath the plasma membrane which plays a critical role in preserving cell morphology and plasma membrane integrity. The aim of this study was to examine the effect of cold/warming exposure on apoptotic microtubules and plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptotic H460 cells that cold/warming exposure disorganized apoptotic microtubules and allowed the access of active caspases to the cellular cortex and the cleavage of essential proteins in the preservation of plasma membrane permeability. Cleavage of cellular cortex and plasma membrane proteins, such as α-spectrin, paxilin, focal adhesion kinase and calcium ATPase pump (PMCA-4) involved in cell calcium extrusion resulted in increased plasma permeability and calcium overload leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the addition of the pan-caspase inhibitor z-VAD during cold/warming exposure that induces AMN depolymerization avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Likewise, apoptotic microtubules stabilization by taxol during cold/warming exposure also prevented cellular cortex and plasma membrane protein cleavage and secondary necrosis. Furthermore, microtubules stabilization or caspase inhibition during cold/warming exposure was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that cold/warming exposure of apoptotic cells induces secondary necrosis which can be prevented by both, microtubule stabilization or caspase inhibition.

Avascular necrosis of the femoral head in children with acute lymphoblastic leukemia: a 4- to 9-year follow-up study.

PubMed

Madadi, Firooz; Shamsian, Bibi Shahin; Alavi, Samin; Madadi, Firoozeh; Eajazi, Alireza; Aslani, Afshin

2011-10-05

Avascular necrosis of the femoral head is usually seen in children aged 1.5 to 10 years, reaching a peak incidence between the ages of 4 and 9. Avascular necrosis of the femoral head is a known complication of corticosteroid therapy in acute lymphoblastic leukemia. There are few reports in the literature regarding the natural history of this condition, and there is no consensus on its management. This study examined the natural history of avascular necrosis of the femoral head in children with leukemia. From 1993 to 2006, a total of 865 children with acute lymphoblastic leukemia were admitted to the hematology-oncology ward of a children's hospital. The diagnosis of acute lymphoblastic leukemia was established by bone marrow aspiration. Based on clinical and radiographic findings, avascular necrosis of the femoral head was found in 7 patients; these patients underwent follow-up for 4 to 9 years. Avascular necrosis of the femoral head was clinically symptomatic in all of the children, and they had advanced radiographic collapse of the femoral head. However, the head of the femur was not at risk in any patient based on clinical and radiographic findings. Patients received supportive treatment such as abduction brace and physiotherapy. After 4 to 9 years of follow-up, clinical and radiographic results were satisfactory. Provided that the head of the femur is not at risk, avascular necrosis of the femoral head in children with acute lymphoblastic leukemia may be successfully managed with nonoperative care. Copyright 2011, SLACK Incorporated.

Impact of preexisting tumor necrosis on the efficacy of stereotactic radiosurgery in the treatment of brain metastases in women with breast cancer.

PubMed

Xu, Zhiyuan; Marko, Nicholas F; Angelov, Lilyana; Barnett, Gene H; Chao, Samuel T; Vogelbaum, Michael A; Suh, John H; Weil, Robert J

2012-03-01

Breast cancer is the second most common source of brain metastasis. Stereotactic radiosurgery (SRS) can be an effective treatment for some patients with brain metastasis (BM). Necrosis is a common feature of many brain tumors, including BM; however, the influence of tumor necrosis on treatment efficacy of SRS in women with breast cancer metastatic to the brain is unknown. A cohort of 147 women with breast cancer and BM treated consecutively with SRS over 10 years were studied. Of these, 80 (54.4%) had necrosis identified on pretreatment magnetic resonance images and 67 (46.4%) did not. Survival times were computed using the Kaplan-Meier method. Log-rank tests were used to compare groups with respect to survival times, Cox proportional hazards regression models were used to perform univariate and multivariate analyses, and chi-square and Fisher exact tests were used to compare clinicopathologic covariates. Neurological survival (NS) and survival after SRS were decreased in BM patients with necrosis at the time of SRS compared with patients without necrosis by 32% and 27%, respectively (NS median survival, 25 vs 17 months [log-rank test, P = .006]; SRS median survival, 15 vs 11 months [log-rank test, P = .045]). On multivariate analysis, HER2 amplification status and necrosis influenced NS and SRS after adjusting for standard clinical features, including BM number, size, and volume as well as Karnofsky performance status. Neuroimaging evidence of necrosis at the time of SRS significantly diminished the efficacy of therapy and was a potent prognostic marker. Copyright © 2011 American Cancer Society.

Total Hip Arthroplasty in Patients With Avascular Necrosis After Hematopoietic Stem Cell Transplantation.

PubMed

Vijapura, Anita; Levine, Harlan B; Donato, Michele; Hartzband, Mark A; Baker, Melissa; Klein, Gregg R

2018-03-01

The immunosuppressive regimens required for hematopoietic stem cell transplantation predispose recipients to complications, including avascular necrosis. Cancer-related comorbidities, immunosuppression, and poor bone quality theoretically increase the risk for perioperative medical complications, infection, and implant-related complications in total joint arthroplasty. This study reviewed 20 primary total hip arthroplasties for avascular necrosis in 14 patients. Outcomes were assessed at routine clinical visits and Harris hip scores were calculated. Follow-up radiographs were evaluated for component malposition, loosening, polyethylene wear, and osteolysis. Average follow-up was 44.5 months for all patients. Postoperative clinical follow-up revealed good to excellent outcomes, with significant improvement in functional outcome scores. There were no periprosthetic infections or revisions for aseptic loosening. There was 1 dislocation on postoperative day 40, which was treated successfully with a closed reduction. Two patients with a prior history of venous thromboembolism developed a pulmonary embolus on postoperative day 13 and 77, respectively. Four patients died several months to years after arthroplasty of complications unrelated to the surgical procedure. Total hip arthroplasty can both be safely performed and greatly improve quality of life in recipients of hematopoietic stem cell transplantation who develop avascular necrosis. However, prolonged venous thromboembolism prophylaxis should be carefully considered in this high-risk patient population. [Orthopedics. 2018; 41(2):e257-e261.]. Copyright 2018, SLACK Incorporated.

The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.

PubMed

Pung, Yuh Fen; Chilian, William M; Bennett, Martin R; Figg, Nichola; Kamarulzaman, Mohd Hamzah

2017-03-01

Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia. NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN. Copyright © 2017 the American Physiological Society.

Acute retinal necrosis complicating chicken pox in a healthy adult: a case report and review of literature.

PubMed

Tajunisah, Iqbal; Reddy, Sagili Chandrasekhara

2007-01-01

We report a case of unilateral acute retinal necrosis (ARN) with marked vitritis and retinal necrosis leading to retinal breaks following chicken pox successfully treated with intravenous acyclovir followed by oral acyclovir, orbital floor triamcinolone injections to contain the inflammation, and barrier laser therapy to secure the retinal breaks with good visual outcome. This case is unusual in its severity and the novel use orbital floor triamcinolone therapy to contain ARN inflammation.

Diffuse FDG uptake due to fat necrosis following transverse rectus abdominus myocutaneous (TRAM) flap reconstruction.

PubMed

Dobbs, Nathan B; Latifi, Hamid R

2013-08-01

We report a case of a 57-year-old female patient with right breast invasive ductal carcinoma. Bilateral mastectomy and TRAM flap reconstructions were performed. Postoperatively, a palpable focus was identified within the left breast. PET/CT showed hypermetabolism throughout the reconstructed left breast, correlating with mixed fat attenuation and inflammatory soft tissue. MRI showed extensive fat necrosis/oil cyst formation in the left breast. As a TRAM flap reconstruction with fat-rich tissue can be damaged intraoperatively due to surgical manipulation, abnormal FDG uptake in this setting is more likely related to fat necrosis than recurrent tumor.

[Building immune microsphere against tumor necrosis factor-alpha (TNF-alpha)].

PubMed

Wang, Qin; Wu, Xiongfei; Wang, Junxia; Liu, Hong; Li, Lian; Jin, Xiyu

2005-12-01

We have constructed the immune microsphere against tumor necrosis factor-alpha (TNF-alpha) prospectively, hoping to establish the experiment groundwork in more researches which could be used in specific elimination of the TNF-alpha by blood purification method for the future. The recombinant human tumor necrosis factor-alpha monoclonal antibody (rHTNF-alpha McAb) was wrapped on the polystyrene microsphere (PSM) carrier connecting poly-L-lysine (PLL) beforehand. They were earmarked by the fluorescein isothiocyanate (FITC) respectively. The packing conditions were examined using the inversted and fluorescence microscopes and the spectrophotometer. The results showed that the best conditions for wrapping were 20 degrees C, pH9.5 and 60 minutes. The PLL content was not changed in the washing fluid after coating, which indicated the wrapping was quite firm. At the same temperature and same coating time, the rHTNF-alpha McAb coated on the PLL was obviously substantial when the concentration of glutaraldehyde solution was 0.2%. The findings demonstrated that the built immune microsphers can be used as a novel adsorption material. This method is simple and economic, and it offers a new approach to the related studies.

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

PubMed

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

2016-06-10

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.

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

Characterization of necrosis-inducing NLP proteins in Phytophthora capsici.

PubMed

Feng, Bao-Zhen; Zhu, Xiao-Ping; Fu, Li; Lv, Rong-Fei; Storey, Dylan; Tooley, Paul; Zhang, Xiu-Guo

2014-05-08

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. 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. 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 PcNLP2, PcNLP6, and PcNLP14 may

Comparative evaluation of HMG CoA reductase inhibitors in experimentally-induced myocardial necrosis: Biochemical, morphological and histological studies.

PubMed

Variya, Bhavesh C; Patel, Snehal S; Trivedi, Jinal I; Gandhi, Hardik P; Rathod, S P

2015-10-05

The present study was carried out to evaluate the protective effect of different statins on isoproterenol (ISO) induced myocardial necrosis. Atorvastatin, rosuvastatin, fluvastatin, simvastatin and pravastatin (10 mg/kg/day) were administered for 12 weeks. After pretreatment of 12 weeks myocardial necrosis was induced by subsequent injection of ISO (85 mg/kg/day, s.c.) to wistar rats. Serum biochemical parameters like glucose, lipid profile, cardiac markers and transaminases were evaluated. Animals were killed and heart was excised for histopathology and antioxidant study. Statins pretreated rats showed significant protection against ISO induced elevation in serum biochemical parameters and serum level of cardiac marker enzymes and transaminase level as compared to ISO control group. Mild to moderate protection was observed in different statins treated heart in histopathology and TTC stained sections. Result from our study also revealed that statins could efficiently protect against ISO intoxicated myocardial necrosis by impairing membrane bound enzyme integrity and endogenous antioxidant enzyme levels. Amongst all statins used, rosuvastatin and pravastatin were found to have maximum cardio-protective activity against ISO induced myocardial necrosis as compared to other statins. Copyright © 2015 Elsevier B.V. All rights reserved.

Necrosis and Apoptosis in Hepatocellular Carcinoma Following Low-Dose Versus High-Dose Preoperative Chemoembolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu Wei, E-mail: dr-lw@163.com; Li Yanhao, E-mail: liyanhao@fimmu.com; He Xiaofeng

Our purpose was to study necrosis and apoptosis of hepatocellular carcinoma (HCC) cells after preoperative transcatheter arterial chemoembolization (TACE) with use of low-dose and high-dose anticancer drugs in HCCs. Fifty-four patients with advanced but surgically resectable HCC were studied. Thirty-four patients who elected to undergo preoperative superselective TACE were randomized to low- and high-dose TACE. Patients in group A (n = 16) received low-dose anticancer drugs: 2 mg mitomycin C (MMC), 10 mg epirubicin (EPI), and 100 mg carboplatin (CBP). Patients in group B (n = 18) were given high doses of anticancer drugs (10 mg MMC, 40 mg EPI,more » and 300 mg CBP). Hepatic resection was subsequently performed. Group C comprised 20 patients who underwent resection without TACE. In all patients the necrosis rates and apoptosis index of tumor cells were evaluated by pathologic examinations and terminal deoxynucleotidyl transferase-mediated nick-end labeling assay. There was no significant difference between group A and group B in tumor response (p > 0.05) after TACE. Necrosis rates in groups A, B, and C were 88.4 {+-} 11.1%, 87.1 {+-} 12.5%, and 7.3 {+-} 3.5%, respectively. There was no significant difference between group A and group B (p > 0.05), while statistical difference was found between group A and group C (p < 0.001) and between group B and group C (p < 0.001). Apoptosis indexes in the three groups were 11.0 {+-} 4.0%, 10.7 {+-} 3.9%, and 5.6 {+-} 2.6%, respectively. Statistical difference exhibited between group A and group C (p < 0.001) and group B versus group C (p < 0.001). No significant difference was observed between group A and group B (p > 0.05). In conclusion, superselective TACE with low- and high-dose chemotherapeutic agents induced similar degrees of cellular apoptosis and necrosis.« less

Caspase blockade induces RIP3-mediated programmed necrosis in Toll-like receptor-activated microglia.

PubMed

Kim, S J; Li, Jianrong

2013-07-11

Microglia are the resident immune cells in the central nervous system and key players against pathogens and injury. However, persistent microglial activation often exacerbates pathological damage and has been implicated in many neurological diseases. Despite their pivotal physiological and pathophysiological roles, how the survival and death of activated microglia is regulated remains poorly understood. We report here that microglia activated through Toll-like receptors (TLRs) undergo RIP1/RIP3-dependent programmed necrosis (necroptosis) when exposed to the pan caspase inhibitor zVAD-fmk. Although zVAD-fmk and the caspase-8 inhibitor IETD-fmk had no effect on unstimulated primary microglia, they markedly sensitized microglia to TLR1/2,3,4,7/8 ligands or TNF treatment, triggering programmed necrosis that was completely blocked by R1P1 kinase inhibitor necrostatin-1. Interestingly, necroptosis induced by TLR ligands and zVAD was restricted to microglial cells and was not observed in astrocytes, neurons or oligodendrocytes even though they are known to express certain TLRs. Deletion of genes encoding TNF or TNFR1 failed to prevent lipopolysaccharide- and poly(I:C)-induced microglial necroptosis, unveiling a TNF-independent programmed necrosis pathway in TLR3- and TLR4-activated microglia. Microglia from mice lacking functional TRIF were fully protected against TLR3/4 activation and zVAD-fmk-induced necrosis, and genetic deletion of rip3 also prevented microglia necroptosis. Activation of c-jun N-terminal kinase and generation of specific reactive oxygen species were downstream signaling events required for microglial cell death execution. Taken together, this study reveals a robust RIP3-dependent necroptosis signaling pathway in TLR-activated microglia upon caspase blockade and suggests that TLR signaling and programmed cell death pathways are closely linked in microglia, which could contribute to neuropathology and neuroinflammation when dysregulated.

Vascular peroxide 1 promotes ox-LDL-induced programmed necrosis in endothelial cells through a mechanism involving β-catenin signaling.

PubMed

Zhang, Yin-Zhuang; Wang, Lei; Zhang, Jie-Jie; Xiong, Xiao-Ming; Zhang, Di; Tang, Xuan-Meng; Luo, Xiu-Ju; Ma, Qi-Lin; Peng, Jun

2018-05-03

Vascular peroxidase 1 (VPO1) plays a key role in mediation of cardiovascular oxidative injury. This study aims to determine whether VPO1 can promote programmed necrosis of endothelial cells and the underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low-density lipoprotein (ox-LDL, 100 μg/mL) for 48 h to induce cell injury, which showed an elevation in cell necrosis (reflected by the increased propidium iodide (PI) positive-staining cells, LDH release and decreased cell viability), concomitant with an increase in programmed necrosis-relevant proteins including receptor-interacting protein kinase 1/3 (RIPK1/3), p-RIPK3 and mixed lineage kinase domain like (MLKL); these phenomena were attenuated by necrostatin-1(Nec-1) and RIPK3 siRNA. Meanwhile, VPO1 was up-regulated in ox-LDL-treated endothelial cells accompanied by a decrease in GSK-3β activity and p-β-catenin levels, and an elevation of β-catenin levels; these phenomena were reversed in the presence of VPO1 siRNA or hypochlorous acid (HOCl) inhibitor; replacement of ox-LDL with HOCl could also induce endothelial programmed necrosis and activate the β-catenin signaling; β-catenin inhibitor could also suppress ox-LDL-induced RIPK-dependent necrosis. In hyperlipidemic patients, the plasma level of VPO1 was obviously increased concomitant with an elevation in plasma levels of RIPK1, RIPK3 and MLKL, and they were positively correlated. VPO1 plays an important role in promotion of endothelial programmed necrosis under hyperlipidemic conditions through activation of β-catenin signaling. It may serve as a novel therapeutic target for prevention of endothelial dysfunction in hyperlipidemia. Copyright © 2018 Elsevier B.V. All rights reserved.

Growth promotion in plants by rice necrosis mosaic virus.

PubMed

Ghosh, S K

1982-08-01

Ludwigia perennis L. infected with rice necrosis mosaic virus (RNMV) showed an increase in both shoot growth and leaf size, along with characteristic chlorotic lesions on leaves. The promotion of growth over the controls extended over a considerable period of time (70 d). Inoculation with RNMV resulted in increased plant height, leaf size, stem diameter, and number and size of fiber bundles in Corchorus olitorius L., C. capsularis L., Hibiscus sabdariffa L. and H. cannabinus L.

Tissue necrosis following extravasation of acyclovir in an adolescent: A case report.

PubMed

Neocleous, Charalambos; Andonopoulou, Eleni; Adramerina, Alkistis; Pegkou, Antigoni; Savelieva, Olga; Georgiadou, Petroula; Drikos, Ioannis

2017-05-01

Extravasation of intravenously infused vesicant solutions is a common problem in medical practice, which can lead to severe and progressive tissue dysfunction, ranging from persistent tissue oedema and fibrosis to delayed tissue necrosis. Acyclovir is a known vesicant medication administrated in paediatric patients, which appears to irritate venous and soft tissue if extravasated. We present the first case involving the extravasation of intravenously infused acyclovir in a female adolescent patient, which caused tissue necrosis and left behind a residual scar lesion. Nursing and medical staff should be aware of the potential dermatological side effects of intravenously infused acyclovir and other medications, even a long time after infusion, and the possible lack of initial local symptoms and signs. Early recognition of extravasation and prompt management are critical in preventing further morbidity, and optimizing outcomes. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Expression of tumour necrosis factor alpha and accumulation of fibronectin in coronary artery restenotic lesions retrieved by atherectomy.

PubMed Central

Clausell, N.; de Lima, V. C.; Molossi, S.; Liu, P.; Turley, E.; Gotlieb, A. I.; Adelman, A. G.; Rabinovitch, M.

1995-01-01

BACKGROUND--The formation of coronary artery neointima experimentally induced in piglets after cardiac transplantation is related to an immune-inflammatory reaction associated with increased expression of T cells and inflammatory mediators (tumour necrosis factor alpha and interleukin 1 beta) and upregulation of fibronectin. In vivo blockade of tumour necrosis factor alpha in rabbits after cardiac transplantation results in reduced neointimal formation. The objective of this study was to investigate the hypothesis that coronary restenosis after atherectomy or percutaneous balloon angioplasty is associated with a similar inflammatory cascade initiated by mechanical injury. METHODS--Specimens taken at coronary atherectomy were analysed from 16 patients. Nine had had the procedure performed twice, firstly, to remove a primary lesion, and secondly, to remove a restenotic lesion. Seven had percutaneous balloon angioplasty after removal of restenotic tissue. Coronary atherectomy specimens were analysed by immunohistochemistry for the presence of T cells, macrophages, major histocompatibility complex II, interleukin 1 beta, tumour necrosis factor alpha, fibronectin, and the receptor for hyaluronan mediated motility. RESULTS--The groups were clinically and angiographically similar with equivalent lumens before and after atherectomy. Restenotic lesions had increased expression of tumour necrosis factor alpha and fibronectin compared with the primary lesions (P < 0.05 for both). There was also a trend towards a greater number of T cells and increased expression of interleukin 1 beta. CONCLUSIONS--Restenosis is associated with increased expression of tumour necrosis factor alpha and fibronectin, suggesting that an immune-inflammatory reaction probably contributes to neointimal formation and may represent a form of wound healing and repair secondary to mechanical injury. Images PMID:7626352

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake.

PubMed

Ferdek, Pawel E; Jakubowska, Monika A; Gerasimenko, Julia V; Gerasimenko, Oleg V; Petersen, Ole H

2016-11-01

Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas. Bile acids are known to induce Ca 2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored. Here we show that cholate and taurocholate elicit more dramatic Ca 2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3-sulfate primarily affects acinar cells. Ca 2+ signals and necrosis are strongly dependent on extracellular Ca 2+ as well as Na + ; and Na + -dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells. Bile acid-mediated pancreatic damage can be further escalated by bradykinin-induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca 2+ signals and necrosis in acinar cells. However, bile acid-elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca 2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3-sulfate (TLC-S), known to induce Ca 2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca 2+ signals on extracellular Na + and the presence of sodium-taurocholate cotransporting polypeptide (NTCP) indicate a Na + -dependent bile acid

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

PubMed Central

Jakubowska, Monika A.; Gerasimenko, Julia V.; Gerasimenko, Oleg V.; Petersen, Ole H.

2016-01-01

Key points Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas.Bile acids are known to induce Ca2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored.Here we show that cholate and taurocholate elicit more dramatic Ca2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3‐sulfate primarily affects acinar cells.Ca2+ signals and necrosis are strongly dependent on extracellular Ca2+ as well as Na+; and Na+‐dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells.Bile acid‐mediated pancreatic damage can be further escalated by bradykinin‐induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Abstract Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid‐elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3‐sulfate (TLC‐S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium–taurocholate cotransporting polypeptide (NTCP) indicate a Na

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

HOW to Differentiate Dutch Elm Disease from Elm Phloem Necrosis

Treesearch

Lester Paul Gibson; Arthur R. Hastings; Leon A. LeMadeliene

1981-01-01

Dutch elm disease (DED) and elm phloem necrosis are the two most serious diseases of elm in the United States (Figs. 1 and 2). Most native species of elm are susceptible to both diseases. Dutch elm disease is caused by a fungus, Ceratocystis u1mi (Buisman) C. Moreau, and is transmitted by two species of elm bark beetles-the smaller European elm bark beetle, Scolytus...

Purtscher's retinopathy and renal cortical necrosis: two rare vaso-occlusive complications in a patient with acute pancreatitis: a case report.

PubMed

Haque, Wasim Md Mohosin Ul; Ananna, Mehruba Alam; Haque, Hasna Fahmima; Rahim, Muhammad Abdur; Samad, Tabassum; Iqbal, Sarwar

2016-11-15

Purtscher's retinopathy and renal cortical necrosis are two rare vaso-occlusive complications of acute pancreatitis. Purtscher's retinopathy causes sudden impairment of vision, which was first reported in a patient with head trauma. Subsequently, it was also reported as a complication of acute pancreatitis and few other clinical conditions. Acute pancreatitis also rarely causes renal cortical necrosis leading to acute kidney injury. However, the simultaneous presence of both complications is rarely reported. A 20-year-old Bengali man presented to our hospital with a history of acute upper abdominal pain, vomiting, anuria, and disorientation. He was ultimately found to have bilateral complete blindness due to Purtscher's retinopathy and acute kidney injury due to renal cortical necrosis, as sequelae of acute pancreatitis. He became dialysis-dependent, his vision did not recover, and he died 16 months after diagnosis. This case highlights Purtscher's retinopathy and renal cortical necrosis might be considered as a recognized pair complication of acute pancreatitis.

Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity and pharynx.

PubMed

Alexander, David; Alexander, Keith; Valentino, Joseph

2012-11-01

Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid transmucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Retrospective chart review. Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. The majority of patients will initially deny the behavior, frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow-up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented, with one resulting in death. The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue, which can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Intranasal tissue necrosis associated with opioid abuse: Case report and systematic review.

PubMed

Morrison, Danielle A; Wise, Sarah K; DelGaudio, John M; Chowdhury, Naweed I; Levy, Joshua M

2017-12-27

Opioid abuse is a common disorder affecting over 2 million Americans. Intranasal tissue necrosis is a previously described sequela of nasal opioid inhalation, with a similar presentation to invasive fungal rhinosinusitis (IFRS). The goal of this case report and systematic review is to evaluate the evidence supporting this uncommon disease, with qualitative analysis of the presentation, management and treatment outcomes. MEDLINE, EMBASE, Google Scholar, Scopus, and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilized to identify English-language studies reporting intranasal mucosal injury associated with prescription opioid abuse. Primary outcomes included clinical presentation, treatment strategies, and outcomes. Systematic review identified 61 patients for qualitative analysis. Common clinical features include facial pain without a history of chronic sinusitis or known immunodeficiency. Diagnostic nasal endoscopy revealed superficial debris with underlying tissue necrosis, consistent with a preliminary diagnosis of IFRS. Characteristic pathologic findings include mucosal ulceration with an overlying acellular substrate, often with polarizable material. Fungal colonization is often reported, with several accounts of angiocentric invasion in immunocompetent patients. Complete symptom resolution is expected following surgical debridement with cessation of intranasal opioid inhalation, with 89% of identified patients experiencing a complete resolution of disease. Intranasal opioid abuse is a prevalent condition associated with chronic pain and tissue necrosis that is clinically concerning for invasive fungal disease. Whereas IFRS must be excluded, even in patients without known immunodeficiency, complete resolution of symptoms can be expected following surgical debridement with cessation of opioid abuse. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Interaction between Cucumber mosaic virus 2b protein and plant catalase induces a specific necrosis in association with proteasome activity.

PubMed

Murota, Katsunori; Shimura, Hanako; Takeshita, Minoru; Masuta, Chikara

2017-01-01

Cucumber mosaic virus (CMV) can induce a specific necrosis on Arabidopsis through the interaction between the CMV 2b protein and host catalase, in which the ubiquitin-proteasome pathway may be involved. We previously reported that the CMV 2b protein, the viral RNA silencing suppressor, interacted with the H 2 O 2 scavenger catalase (CAT3), leading to necrosis on CMV-inoculated Arabidopsis leaves. We here confirmed that CMV could more abundantly accumulate in the CAT3-knockout mutant (cat3), and that CAT3 makes host plants a little more tolerant to CMV. We also found that the necrosis severity is not simply explained by a high level of H 2 O 2 given by the lack of CAT3, because the recombinant CMV, CMV-N, induced much milder necrosis in cat3 than in the wild type, suggesting some specific mechanism for the necrosis induction. To further characterize the 2b-inducing necrosis in relation to its binding to CAT3, we conducted the agroinfiltration experiments to overexpress CAT3 and 2b in N. benthamiana leaves. The accumulation levels of CAT3 were higher when co-expressed with the CMV-N 2b (N2b) than with CMV-Y 2b (Y2b). We infer that N2b made a more stable complex with CAT3 than Y2b did, and the longevity of the 2b-CAT3 complex seemed to be important to induce necrosis. By immunoprecipitation (IP) with an anti-ubiquitin antibody followed by the detection with anti-CAT3 antibodies, we detected a higher molecular-weight smear and several breakdown products of CAT3 among the IP-proteins. In addition, the proteasome inhibitor MG132 treatment could actually increase the accumulation levels of CAT3. This study suggests that the host proteasome pathway is, at least partially, responsible for the degradation of CAT3, which is manifested in CMV-infected tissues.

The predictive and prognostic value of tumour necrosis in muscle invasive bladder cancer patients receiving radiotherapy with or without chemotherapy in the BC2001 trial (CRUK/01/004)

PubMed Central

Choudhury, Ananya; West, Catharine M; Porta, Nuria; Hall, Emma; Denley, Helen; Hendron, Carey; Lewis, Rebecca; Hussain, Syed A; Huddart, Robert; James, Nicholas

2017-01-01

Background: Severe chronic hypoxia is associated with tumour necrosis. In patients with muscle invasive bladder cancer (MIBC), necrosis is prognostic for survival following surgery or radiotherapy and predicts benefit from hypoxia modification of radiotherapy. Adding mitomycin C (MMC) and 5-fluorouracil (5-FU) chemotherapy to radiotherapy improved locoregional control (LRC) compared to radiotherapy alone in the BC2001 trial. We hypothesised that tumour necrosis would not predict benefit for the addition of MMC and 5-FU to radiotherapy, but would be prognostic. Methods: Diagnostic tumour samples were available from 230 BC2001 patients. Tumour necrosis was scored on whole-tissue sections as absent or present, and its predictive and prognostic significance explored using Cox proportional hazards models. Survival estimates were obtained by Kaplan–Meier methods. Results: Tumour necrosis was present in 88/230 (38%) samples. Two-year LRC estimates were 71% (95% CI 61–79%) for the MMC/5-FU chemoradiotherapy group and 49% (95% CI 38–59%) for the radiotherapy alone group. When analysed by tumour necrosis status, the adjusted hazard ratios (HR) for MMC/5-FU vs. no chemotherapy were 0.46 (95% CI: 0.12–0.99; P=0.05, necrosis present) and 0.55 (95% CI: 0.31–0.98; P=0.04, necrosis absent). Multivariable analysis of prognosis for LRC by the presence vs. absence of necrosis yielded a HR=0.89 (95% CI 0.55–1.44, P=0.65). There was no significant association for necrosis as a predictive or prognostic factor with respect to overall survival. Conclusions: Tumour necrosis was neither predictive nor prognostic, and therefore MMC/5-FU is an appropriate radiotherapy-sensitising treatment in MIBC independent of necrosis status. PMID:28125821

Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

PubMed

Yang, Chen; Huang, Junlin; Huang, Xiaowen; Huang, Shaozhuo; Cheng, Jiaxin; Liao, Weixin; Chen, Xuewen; Wang, Xueyi; Dai, Shixue

2018-05-12

The association between anti-tumor necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumor necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. MEDLINE, EMBASE and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumor necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. Twelve studies comprising 285811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumor necrosis factor alpha agents exposed and anti-tumor necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR], 1.43 95%CI, 0.91-2.25, p= 0.116; random effects: risk ratio [RR], 0.83 95%CI, 0.47-1.48, p=0.534). However, monotherapy of anti-tumor necrosis factor alpha agents (random effects: IRR=1.65, 95%CI, 1.16-2.35; p=0.006; random effects: RR=1.00, 95%CI, 0.39-2.59; p=0.996) or combination therapy (random effects: IRR=3.36, 95%CI, 2.23-5.05; p< 0.001; random effects: RR=1.90, 95%CI, 0.66-5.44; p=0.233) can significantly increase the risk of lymphoma. Exposition of anti-tumor necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumor necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.

Rapid simultaneous determination of apoptosis, necrosis, and viability in sulfur mustard exposed HaCaT cell cultures.

PubMed

Heinrich, A; Balszuweit, F; Thiermann, H; Kehe, K

2009-12-15

Sulfur mustard (SM; bis(2-chloroethyl)sulphide; HD) is a blister inducing agent causing DNA damage and subsequently, cell death, mostly by apoptosis in basal keratinocytes. Despite intensive investigations on the cellular mechanism, there are, as of now, no causal therapeutics to prevent or antagonize SM-related damage to cells and tissues. In order to develop treatment strategies against vesication, it is important to distinguish apoptosis from necrosis in SM treated human keratinocytes. DNA fragmentation is a hallmark of apoptosis and regulated by a cascade of enzymes (endonucleases, DNase I, NUC 18), which finally cut the chromatin into specific formations of 180-200 base pairs, the nucleosomes. A feasible way to monitor apoptosis is the detection of nucleosomes by means of the Cell Death Detection ELISA(plus) (CDDE). In contrast, during necrosis DNA fragmentation is at random and delivers larger fragments, which therefore are significantly less in number and predominantly occur in cell culture supernatant. To monitor necrosis, we measured the release of intracellular adenylate kinase (AK) into cell culture supernatant by means of the ToxiLight Bioluminescence Assay (TL). With combination of the Cell Death Detection ELISA(plus) and the ToxiLight Bioluminescence Assay, we acquired more comprehensive information on cell survival and mechanisms of cell death, following an SM exposure. To validate the assay we tested common apoptosis- and necrosis-inducing agents like SM 300 microM for 30 min, Lewisite (L) 60 microM for 5 min and Triton X-100 0.1%. The results show that it is possible to differentiate between the two modes of cell death and to quantify their extent. This assay is highly effective in quantifying apoptosis and necrosis caused by cytotoxic agents and in estimating protective effects of potential active pharmaceutical ingredients.

FPLC and liquid-chromatography mass spectrometry identify candidate necrosis-inducing proteins from culture filtrates of the fungal wheat pathogen Zymoseptoria tritici

USDA-ARS?s Scientific Manuscript database

Culture filtrates (CFs) of the fungal wheat pathogen Zymoseptoria tritici were assayed for necrosis-inducing activity after infiltration in leaves of various wheat cultivars. Active fractions were partially purified and characterized. The necrosis-inducing factors in CFs are proteinaceous, heat st...

The Major Acute-Phase Protein, Serum Amyloid P Component, in Mice Is Not Involved in Endogenous Resistance against Tumor Necrosis Factor Alpha-Induced Lethal Hepatitis, Shock, and Skin Necrosis

PubMed Central

Van Molle, Wim; Hochepied, Tino; Brouckaert, Peter; Libert, Claude

2000-01-01

The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) induces lethal hepatitis when injected into d-(+)-galactosamine-sensitized mice on the one hand or systemic inflammatory response syndrome (SIRS) in normal mice on the other hand. We studied whether serum amyloid P component (SAP), the major acute-phase protein in mice, plays a protective role in both lethal models. For this purpose, we used SAP0/0 mice generated by gene targeting. We studied the lethal response of SAP0/0 or SAP+/+ mice to both lethal triggers but found no differences in the sensitivity of both types of mice. We also investigated whether SAP is involved in establishing two types of endogenous protection: one using a single injection of interleukin-1β (IL-1β) for desensitization and clearly involving a liver protein, the other by tolerizing mice for 5 days using small doses of human TNF-α. Although after IL-1β or after tolerization the SAP levels in the serum had risen fourfold in the control mice and not in the SAP0/0 mice, the same extents of desensitization and tolerization were achieved. Finally, we observed that the induction of hemorrhagic necrosis in the skin of mice by two consecutive local injections with TNF-α was not altered in SAP0/0 mice. We conclude that the presence or absence of SAP has no influence on the sensitivity of mice to TNF-α-induced hepatitis, SIRS, and hemorrhagic necrosis or on the endogenous protective mechanisms of desensitization or tolerization. PMID:10948120

Tumor necrosis factor alpha and pulmonary function in Saskatchewan grain handlers.

PubMed

McDuffie, Helen H; Nakagawa, Kazuko; Pahwa, Punam; Shindo, Junichi; Hashimoto, Mirai; Nakada, Naoyuki; Ghosh, Sunita; Kirychuk, Shelley P; Hucl, Pierre

2006-05-01

The objective of this study was to estimate the contribution of lifestyle (cigarettes) and tumor necrosis factor (TNF) alpha polymorphisms at position 308 of the tumor necrosis factor alpha gene promotor (TNF-308*1/*2) to pulmonary function among grain handlers. Employed male grain handlers (157) provided occupational and respiratory symptom information, pulmonary function measurements, and DNA for genotyping. The genotypes of 101 were TNF-308*1/*1, 47 were *1/*2, and nine were *2/*2. Current smokers whose genotype was *2/*2 or *1/*2 had lower values compared with other combinations of genotype and smoking status. Among *1/*1 homozygotes, current smokers had better percent of predicted forced expiratory volume in 1 second (P = 0.04) mean values than nonsmokers and better percent of predicted forced vital capacity than exsmokers (P = 0.017) or nonsmokers (P = 0.008). These results indicate the complexity of determining which workers will develop acute and chronic adverse pulmonary conditions in response to exposure to grain dust and the toxins in cigarette smoke interacting with their genotype.

Subcutaneous injection of liquid and foamed polidocanol: extravasation is not responsible for skin necrosis during reticular and spider vein sclerotherapy.

PubMed

Schuller-Petrović, S; Pavlović, M D; Neuhold, N; Brunner, F; Wölkart, G

2011-08-01

Cutaneous necrosis is one of the most annoying complications of reticular and spider vein sclerotherapy. The precise incidence of the complication is not known, although various sources reported incidence between 0.2% and 1.2%. Among a few mechanisms proposed to explain it, extravasation of the sclerosant into the perivascular tissue has been cited as the major cause. The aim of the experimental study in rats was to examine the potential of various concentrations and volumes of polidocanol in both liquid and foam forms to cause cutaneous necrosis after superficial subcutaneous injection. Twenty-four female Sprague Dawley rats were injected subcutaneously different concentrations (0.5%, 1%, 2% and 3%) of polidocanol as well as different preparations of polidocanol (liquid vs. foam) and volumes (0.1-0.5 mL). The animals were sacrificed 10 days after injections and biopsy specimens were obtained. Cutaneous necrosis was not seen at volumes <0.5 mL regardless of the concentration or form of polidocanol injected. Foam preparation was shown to be less potent in inducing necrosis with a minimal strength being 2% in comparison with the liquid form where 1% was sufficient to produce overt cutaneous necrosis. This experimental study shows that extravasation of polidocal in usual circumstances of sclerotherapy of spider and reticular veins cannot be a significant cause of cutaneous necrosis rarely observed in this setting. It is particularly true for the foamed polidocanol where 1% strength seems safe if injected extravascularly in volumes up to 0.5 mL. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Viral erythrocytic necrosis: Chapter 2.2.7

USGS Publications Warehouse

Winton, James R.; Hershberger, Paul K.

2014-01-01

In spite of extensive efforts, the etiological agent of VEN has not been propagated in fish cell lines making its characterization difficult. However, transmission electron microscopy (TEM) of red blood cells from diseased fish convincingly demonstrates the presence of iridovirus-like particles that have been given the name erythrocytic necrosis virus (ENV). While the ENV virions in red blood cells of various species of fish from differing geographic locations may appear morphologically distinct (Smail 1982; Wolf 1988), at least one strain of ENV has now been partially sequenced, confirming it to be a member of the family Iridoviridae (Emmenegger et al. in press). However, the genetic relatedness of ENV from various fish hosts has not yet been investigated. 

Acute esophageal necrosis and low-flow state

PubMed Central

Burtally, Ahmad; Gregoire, Philippe

2007-01-01

Acute esophageal necrosis (AEN), also called black esophagus, is quite exceptional. Endoscopic findings show circumferential black discolouration of the esophagus with or without exudates. The etiology of AEN is presently unknown and is assumed to be multifactorial. Distal esophageal involvement with proximal extension ending sharply at the gastroesophageal junction is the most common presentation. The present case report describes the clinical and endoscopic evolution of black esophagus observed in a patient with significant peripheral vascular disease, who was presented to the intensive care unit at the Hopital Saint-Francois d’Assise (Quebec City, Quebec). Through an extensive review of the literature, common underlying clinical conditions of patients diagnosed with AEN have been identified. PMID:17431514

[Skin necrosis resulting from the extravasation of intravenous injections].

PubMed

Ikhefoulma, Soumaya; Mahiou, Abelhamid; Perillat, Isabelle

2012-09-01

Extravasation is the diffusion of a product injected intravenously into the perivascular or subcutaneous spaces. Skin necrosis of iatrogenic origin can be observed for example with a subcutaneous perfusion of solution containing potassium chloride or the extravasation of 30% hypertonic glucose serum. Whenever a product is injected, the administration route for which the product has obtained marketing authorisation must be respected and a perfusion time of at least 4 to 5 hours per litre of solution perfused must be observed.

Herpes Simplex Encephalitis during Treatment with Tumor Necrosis Factor-α Inhibitors

PubMed Central

Bradford, Russell D.; Pettit, April C.; Wright, Patty W.; Mulligan, Mark J.; Moreland, Larry W.; McLain, David A.; Gnann, John W.; Bloch, Karen C.

2012-01-01

We report 3 cases of herpes simplex virus encephalitis in patients receiving tumor necrosis factor-alpha (TNF-α) inhibitors for rheumatologic disorders. Although TNF-α inhibitors have been reported to increase the risk of other infectious diseases, to our knowledge, an association between anti–TNF-α drugs and herpes simplex virus encephalitis has not been previously described. PMID:19681709

Tumor necrosis a regulation of adipokine gene expression in neonatal adipose tissue

USDA-ARS?s Scientific Manuscript database

The neonatal period is also a time of significant stress and susceptibility to infection, conditions which favor the secretion of tumor necrosis a. The present study was designed to determine if TNFa can alter adipokine gene expression within the adipose tissue of neonatal swine. Primary stromal v...

Elevated serum tumor necrosis factor-alpha and soluble tumor necrosis factor receptors correlate with aberrant energy metabolism in liver cirrhosis.

PubMed

Shiraki, Makoto; Terakura, Yoichi; Iwasa, Junpei; Shimizu, Masahito; Miwa, Yoshiyuki; Murakami, Nobuo; Nagaki, Masahito; Moriwaki, Hisataka

2010-03-01

Protein-energy malnutrition is frequently observed in patients with liver cirrhosis and is associated with their poor prognosis. Tumor necrosis factor-alpha (TNF-alpha) is elevated in those patients and may contribute to the alterations of energy metabolism. Our aim was to characterize the aberrant energy metabolism in cirrhotic patients with regard to TNF-alpha. Twenty-four patients (mean age 65 +/- 6 y) with viral liver cirrhosis who did not have hepatocellular carcinoma or acute infections were studied. Twelve healthy volunteers were recruited after matching for age, gender, and body mass index with the patients and served as controls (59 +/- 8 y). Serum levels of TNF-alpha, soluble 55-kDa TNF receptor (sTNF-R55), soluble 75-kDa TNF receptor (sTNF-R75), and leptin were determined by immunoassay. Substrate oxidation rates of carbohydrate and fat were estimated by indirect calorimetry after overnight bedrest and fasting. In cirrhotic patients, serum levels of TNF-alpha, sTNF-R55, and sTNF-R75 were significantly higher than those in the controls and correlated with the increasing grade of disease severity as defined by Child-Pugh classification. Serum leptin concentration was not different between cirrhotics and controls but correlated with their body mass index. The decrease in substrate oxidation rate of carbohydrate and the increase in substrate oxidation rate of fat significantly correlated with serum TNF-alpha, sTNF-R55, and sTNF-R75 concentrations. Tumor necrosis factor-alpha might be associated with the aberrant energy metabolism in patients with liver cirrhosis. Copyright (c) 2010 Elsevier Inc. All rights reserved.

The "starfield" pattern of cerebral fat embolism from bone marrow necrosis in sickle cell crisis.

PubMed

Dhakal, Laxmi P; Bourgeois, Kirk; Barrett, Kevin M; Freeman, William D

2015-04-01

Sickle cell disease may manifest with cerebrovascular and systemic complications. Sickle crisis that results in avascular necrosis of long bones with resultant cerebral fat embolism syndrome is rare and has a characteristic "starfield" pattern on MRI. This "starfield" MRI pattern should raise suspicion for sickle cell crisis in patients without a known history of the disease, which can lead to earlier sickle cell red blood cell exchange transfusion and treatment. We present a case of a male who presented emergently with acute seizure, coma with a characteristic MRI pattern, which lead to the diagnosis of avascular bone marrow necrosis and cerebral fat embolism syndrome from sickle cell crisis.

Defining external factors that determine neuronal survival, apoptosis and necrosis during excitotoxic injury using a high content screening imaging platform.

PubMed

Anilkumar, Ujval; Weisova, Petronela; Schmid, Jasmin; Bernas, Tytus; Huber, Heinrich J; Düssmann, Heiko; Connolly, Niamh M C; Prehn, Jochen H M

2017-01-01

Cell death induced by excessive glutamate receptor overactivation, excitotoxicity, has been implicated in several acute and chronic neurological disorders. While numerous studies have demonstrated the contribution of biochemically and genetically activated cell death pathways in excitotoxic injury, the factors mediating passive, excitotoxic necrosis are less thoroughly investigated. To address this question, we developed a high content screening (HCS) based assay to collect high volumes of quantitative cellular imaging data and elucidated the effects of intrinsic and external factors on excitotoxic necrosis and apoptosis. The analysis workflow consisted of robust nuclei segmentation, tracking and a classification algorithm, which enabled automated analysis of large amounts of data to identify and quantify viable, apoptotic and necrotic neuronal populations. We show that mouse cerebellar granule neurons plated at low or high density underwent significantly increased necrosis compared to neurons seeded at medium density. Increased extracellular Ca2+ sensitized neurons to glutamate-induced excitotoxicity, but surprisingly potentiated cell death mainly through apoptosis. We also demonstrate that inhibition of various cell death signaling pathways (including inhibition of calpain, PARP and AMPK activation) primarily reduced excitotoxic apoptosis. Excitotoxic necrosis instead increased with low extracellular glucose availability. Our study is the first of its kind to establish and implement a HCS based assay to investigate the contribution of external and intrinsic factors to excitotoxic apoptosis and necrosis.

Defining external factors that determine neuronal survival, apoptosis and necrosis during excitotoxic injury using a high content screening imaging platform

PubMed Central

Weisova, Petronela; Schmid, Jasmin; Bernas, Tytus; Huber, Heinrich J.; Düssmann, Heiko; Connolly, Niamh M. C.; Prehn, Jochen H. M.

2017-01-01

Cell death induced by excessive glutamate receptor overactivation, excitotoxicity, has been implicated in several acute and chronic neurological disorders. While numerous studies have demonstrated the contribution of biochemically and genetically activated cell death pathways in excitotoxic injury, the factors mediating passive, excitotoxic necrosis are less thoroughly investigated. To address this question, we developed a high content screening (HCS) based assay to collect high volumes of quantitative cellular imaging data and elucidated the effects of intrinsic and external factors on excitotoxic necrosis and apoptosis. The analysis workflow consisted of robust nuclei segmentation, tracking and a classification algorithm, which enabled automated analysis of large amounts of data to identify and quantify viable, apoptotic and necrotic neuronal populations. We show that mouse cerebellar granule neurons plated at low or high density underwent significantly increased necrosis compared to neurons seeded at medium density. Increased extracellular Ca2+ sensitized neurons to glutamate-induced excitotoxicity, but surprisingly potentiated cell death mainly through apoptosis. We also demonstrate that inhibition of various cell death signaling pathways (including inhibition of calpain, PARP and AMPK activation) primarily reduced excitotoxic apoptosis. Excitotoxic necrosis instead increased with low extracellular glucose availability. Our study is the first of its kind to establish and implement a HCS based assay to investigate the contribution of external and intrinsic factors to excitotoxic apoptosis and necrosis. PMID:29145487

A study of tail tip necrosis in young fattening bulls on slatted floors.

PubMed

Madsen, E B; Nielsen, K

1985-01-01

A questionnaire sent to 78 producers revealed that tail tip necrosis was seen only in units with fattening bulls housed on slatted floors. Out of 43 such units, 20 (46.5 per cent) reported that tail tip necrosis was a herd problem. All 43 herds were visited, owners were interviewed and housing and management data recorded. It is concluded that tail tip necrosis is a multifactorial disease. The initial lesion is caused by tramping, but the following factors are essential in the development and severity of the disease, i) slatted concrete floors, ii) close confinement, iii) hot season and iv) body weight above 200 kg. The stocking density (expressed as kg bodyweight per square meter pen) was significantly higher in problem herds (210 kg/m2) than in control herds (165 kg/m2). There was a close relationship between high environmental temperature and tail tip necroses. The majority of incidents occurred during the warm season (May through September), very few cases were seen during the colder months. The general morbidity and mortality rates were significantly higher in problem herds than in control herds. Microbiology of affected tails revealed mixed infections in most cases, with Corynebacterium pyogenes and Bacteroides melaninogenicus as the most frequently isolated organisms. Principles of treatment and prevention are discussed. There is evidence to assume that a 10-20 per cent reduction in stocking density could be an efficient prophylactic measure.

Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

PubMed Central

Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N; de Oliveira, Cristiane; Crowell, Michael D; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I; Khalid, Asif; Whitcomb, David C; DeLany, James P; Cline, Rachel A; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P

2016-01-01

Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP. PMID:25500204

Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T cells

PubMed Central

Tone, Masahide; Tone, Yukiko; Adams, Elizabeth; Yates, Stephen F.; Frewin, Mark R.; Cobbold, Stephen P.; Waldmann, Herman

2003-01-01

Recently, agonist antibodies to glucocorticoid-induced tumor necrosis factor receptor (GITR) (tumor necrosis factor receptor superfamily 18) have been shown to neutralize the suppressive activity of CD4+CD25+ regulatory T cells. It was anticipated that this would be the role of the physiological ligand. We have identified and expressed the gene for mouse GITR ligand and have confirmed that its interaction with GITR reverses suppression by CD4+CD25+ T cells. It also, however, provides a costimulatory signal for the antigen-driven proliferation of naïve T cells and polarized T helper 1 and T helper 2 clones. RT-PCR and mAb staining revealed mouse GITR ligand expression in dendritic cells, macrophages, and B cells. Expression was controlled by the transcription factor NF-1 and potentially by alternative splicing of mRNA destabilization sequences. PMID:14608036

Surgically Induced Scleral Necrosis in a Patient With Rheumatoid Arthritis After AGV Implantation.

PubMed

Kumar, Suresh; Ichhpujani, Parul; Thakur, Sahil

2018-03-01

Surgically induced scleral necrosis (SINS) is a rare entity that has till date not been reported in a patient of glaucoma undergoing Ahmed glaucoma valve (AGV) implantation. We present a case of primary open-angle glaucoma who underwent AGV implantation followed by development of scleral necrosis, involving both the scleral patch graft and host sclera. After failure of surgical and medical management, AGV had to be explanted. The patient was diagnosed with rheumatoid arthritis and had to be treated with steroids and azathioprine for the same. SINS is a potentially disastrous complication of ocular surgery that can occur in patients with systemic diseases like rheumatoid arthritis and requires aggressive management to salvage the eye. SINS can occur with AGV implantation. Treatment may require aggressive medical and surgical intervention. It is imperative to evaluate patients for systemic illness before planning an AGV implant.

Bone marrow necrosis secondary to imatinib usage, mimicking spinal metastasis on magnetic resonance imaging and FDG-PET/CT.

PubMed

Aras, Yavuz; Akcakaya, Mehmet Osman; Unal, Seher N; Bilgic, Bilge; Unal, Omer Faruk

2012-01-01

Imatinib mesylate has become the treatment of choice for gastrointestinal stromal tumors (GISTs) and has made a revolutionary impact on survival rates. Bone marrow necrosis is a very rare adverse event in malignant GIST. Bone metastases are also rarely encountered in the setting of this disease. The authors report on a patient with malignant GIST who developed a bone lesion, mimicking spinal metastasis on both MR imaging and FDG-PET/CT. Corpectomy and anterior fusion was performed, but the pathology report was consistent with bone marrow necrosis. Radiological and clinical similarities made the distinction between metastasis and bone marrow necrosis challenging for the treating physicians. Instead of radical surgical excision, more conservative methods such as percutaneous or endoscopic bone biopsies may be more useful for pathological confirmation, even though investigations such as MR imaging and FDG-PET/CT indicate metastatic disease.

FPLC and liquid-chromatography mass spectrometry identify candidate necrosis-inducing proteins from culture filtrates of the fungal wheat pathogen Zymoseptoria tritici.

PubMed

Ben M'Barek, Sarrah; Cordewener, Jan H G; Tabib Ghaffary, Seyed M; van der Lee, Theo A J; Liu, Zhaohui; Mirzadi Gohari, Amir; Mehrabi, Rahim; America, Antoine H P; Robert, Olivier; Friesen, Timothy L; Hamza, Sonia; Stergiopoulos, Ioannis; de Wit, Pierre J G M; Kema, Gerrit H J

2015-06-01

Culture filtrates (CFs) of the fungal wheat pathogen Zymoseptoria tritici were assayed for necrosis-inducing activity after infiltration in leaves of various wheat cultivars. Active fractions were partially purified and characterized. The necrosis-inducing factors in CFs are proteinaceous, heat stable and their necrosis-inducing activity is temperature and light dependent. The in planta activity of CFs was tested by a time series of proteinase K (PK) co-infiltrations, which was unable to affect activity 30min after CF infiltrations. This suggests that the necrosis inducing proteins (NIPs) are either absent from the apoplast and likely actively transported into mesophyll cells or protected from the protease by association with a receptor. Alternatively, plant cell death signaling pathways might be fully engaged during the first 30min and cannot be reversed even after PK treatment. Further fractionation of the CFs with the highest necrosis-inducing activity involved fast performance liquid chromatography, SDS-PAGE and mass spectrometry. This revealed that most of the proteins present in the fractions have not been described before. The two most prominent ZtNIP encoding candidates were heterologously expressed in Pichia pastoris and subsequent infiltration assays showed their differential activity in a range of wheat cultivars. Copyright © 2015 Elsevier Inc. All rights reserved.

Bilateral avascular necrosis of the femoral head due to the use of heroin: A case report.

PubMed

Ozkunt, Okan; Sarıyılmaz, Kerim; Sungur, Mustafa; Ilen, Ferhat; Dikici, Fatih

2015-01-01

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. 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. 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. Heroin use will be important problem for population. That's why is crucial to understand the effect of heroin. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Colon Necrosis Due to Sodium Polystyrene Sulfonate with and without Sorbitol: An Experimental Study in Rats.

PubMed

Ayoub, Isabelle; Oh, Man S; Gupta, Raavi; McFarlane, Michael; Babinska, Anna; Salifu, Moro O

2015-01-01

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. 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. 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. 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.

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

Intranasal Hydrocodone-Acetaminophen Abuse Induced Necrosis of the Nasal Cavity and Pharynx

PubMed Central

Alexander, David; Alexander, Keith; Valentino, Joseph

2012-01-01

Objectives Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid trans mucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Study Design Retrospective chart review. Methods Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. Results The majority of patients will initially deny the behavior frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented with one resulting in death. Conclusions The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue that can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Study Design Chart review, level of evidence: 4 PMID:22965281

A novel quantitative immunomagnetic reduction assay for Nervous necrosis virus.

PubMed

Yang, Shieh Yueh; Wu, Jen Leih; Tso, Chun Hsi; Ngou, Fang Huar; Chou, Hsin Yiu; Nan, Fan Hua; Horng, Herng Er; Lu, Ming Wei

2012-09-01

Rapid, sensitive, and automatic detection platforms are among the major approaches of controlling viral diseases in aquaculture. An efficient detection platform permits the monitoring of pathogen spread and helps to enhance the economic benefits of commercial aquaculture. Nervous necrosis virus (NNV), the cause of viral encephalopathy and retinopathy, is among the most devastating aquaculture viruses that infect marine fish species worldwide. In the present study, a highly sensitive magnetoreduction assay was developed for detecting target biomolecules with a primary focus on NNV antigens. A standard curve of the different NNV concentrations that were isolated from infected Malabar grouper (Epinephelus malabaricus) was established before experiments were conducted. The test solution was prepared by homogeneous dispersion of magnetic nanoparticles coated with rabbit anti-NNV antibody. The magnetic nanoparticles in the solution were oscillated by magnetic interaction with multiple externally applied, alternating current magnetic fields. The assay's limit of detection was approximately 2 × 10(1) TCID(50)/ml for NNV. Moreover, the immunomagnetic reduction readings for other aquatic viruses (i.e., 1 × 10(7) TCID(50)/ml for Infectious pancreatic necrosis virus and 1 × 10(6.5) TCID(50)/ml for grouper iridovirus) were below the background noise in the NNV solution, demonstrating the specificity of the new detection platform.

Role of tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and associated proteins in coronary artery disease and cardiac events.

PubMed

Chemaly, Melody; McGilligan, Victoria; Gibson, Mark; Clauss, Matthias; Watterson, Steven; Alexander, H Denis; Bjourson, Anthony John; Peace, Aaron

2017-12-01

Tumour necrosis factor alpha converting enzyme (TACE/ADAM17) is a member of the A disintegrin and metalloproteinase (ADAM) family of ectodomain shedding proteinases. It regulates many inflammatory processes by cleaving several transmembrane proteins, including tumour necrosis factor alpha (TNFα) and its receptors tumour necrosis factor alpha receptor 1 and tumour necrosis factor alpha receptor 2. There is evidence that TACE is involved in several inflammatory diseases, such as ischaemia, heart failure, arthritis, atherosclerosis, diabetes and cancer as well as neurological and immune diseases. This review summarizes the latest discoveries regarding the mechanism of action and regulation of TACE. It also focuses on the role of TACE in atherosclerosis and coronary artery disease (CAD), highlighting clinical studies that have investigated its expression and protein activity. The multitude of substrates cleaved by TACE make this enzyme an attractive target for therapy and a candidate for biomarker research and development in CAD. Crown Copyright © 2017. Published by Elsevier Masson SAS. All rights reserved.

Use of the medial femoral condyle vascularized bone flap in traumatic avascular necrosis of the navicular: a case report.

PubMed

Holm, Janson; Vangelisti, Garrett; Remmers, Jared

2012-01-01

The medial femoral condyle vascularized bone flap has a high success rate in published literature regarding its use in nonunions and avascular necrosis of the upper and lower extremities. It is reported to have minimal donor site morbidity and the ability to provide structural support and torsional strength to load-bearing areas. The flap has found particular success in the treatment of scaphoid nonunions. The tarsal navicular, similar to the scaphoid, is largely articular cancellous bone with little surface area for vascular inflow. These anatomic features make the navicular prone to nonunion and avascular necrosis in traumatic scenarios. We describe a case of nonunion and avascular necrosis of the tarsal navicular occurring as sequelae of a high-impact midfoot injury sustained in an automobile accident. After an initial attempt at open reduction and internal fixation with midfoot bridge plating, subsidence and nonunion resulted. An attempt at arthrodesis of the talonavicular and naviculocuneiform joints was then undertaken. This too failed, leading to the development of additional collapse and avascular necrosis. The site was treated with a medial femoral condyle vascularized bone flap. In this single case, the patient returned to pain-free ambulation and reported excellent outcomes and functional capacity. Although we present a successful case, a larger case series is necessary to establish the use of this flap as a reliable option for the treatment of nonunion and avascular necrosis of the tarsal navicular. Copyright © 2012 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

24(S)-hydroxycholesterol induces neuronal cell death through necroptosis, a form of programmed necrosis.

PubMed

Yamanaka, Kazunori; Saito, Yoshiro; Yamamori, Tohru; Urano, Yasuomi; Noguchi, Noriko

2011-07-15

24(S)-Hydroxycholesterol (24S-OHC) produced by cholesterol 24-hydroxylase expressed mainly in neurons plays an important physiological role in the brain. Conversely, it has been reported that 24S-OHC possesses potent cytotoxicity. The molecular mechanisms of 24S-OHC-induced cell death have not yet been fully elucidated. In this study, using human neuroblastoma SH-SY5Y cells and primary cortical neuronal cells derived from rat embryo, we characterized the form of cell death induced by 24S-OHC. SH-SY5Y cells treated with 24S-OHC exhibited neither fragmentation of the nucleus nor caspase activation, which are the typical characteristics of apoptosis. 24S-OHC-treated cells showed necrosis-like morphological changes but did not induce ATP depletion, one of the features of necrosis. When cells were treated with necrostatin-1, an inhibitor of receptor-interacting serine/threonine kinase 1 (RIPK1) required for necroptosis, 24S-OHC-induced cell death was significantly suppressed. The knockdown of RIPK1 by transfection of small interfering RNA of RIPK1 effectively attenuated 24S-OHC-induced cell death. It was found that neither SH-SY5Y cells nor primary cortical neuronal cells expressed caspase-8, which was regulated for RIPK1-dependent apoptosis. Collectively, these results suggest that 24S-OHC induces neuronal cell death by necroptosis, a form of programmed necrosis.

24(S)-Hydroxycholesterol Induces Neuronal Cell Death through Necroptosis, a Form of Programmed Necrosis*

PubMed Central

Yamanaka, Kazunori; Saito, Yoshiro; Yamamori, Tohru; Urano, Yasuomi; Noguchi, Noriko

2011-01-01

24(S)-Hydroxycholesterol (24S-OHC) produced by cholesterol 24-hydroxylase expressed mainly in neurons plays an important physiological role in the brain. Conversely, it has been reported that 24S-OHC possesses potent cytotoxicity. The molecular mechanisms of 24S-OHC-induced cell death have not yet been fully elucidated. In this study, using human neuroblastoma SH-SY5Y cells and primary cortical neuronal cells derived from rat embryo, we characterized the form of cell death induced by 24S-OHC. SH-SY5Y cells treated with 24S-OHC exhibited neither fragmentation of the nucleus nor caspase activation, which are the typical characteristics of apoptosis. 24S-OHC-treated cells showed necrosis-like morphological changes but did not induce ATP depletion, one of the features of necrosis. When cells were treated with necrostatin-1, an inhibitor of receptor-interacting serine/threonine kinase 1 (RIPK1) required for necroptosis, 24S-OHC-induced cell death was significantly suppressed. The knockdown of RIPK1 by transfection of small interfering RNA of RIPK1 effectively attenuated 24S-OHC-induced cell death. It was found that neither SH-SY5Y cells nor primary cortical neuronal cells expressed caspase-8, which was regulated for RIPK1-dependent apoptosis. Collectively, these results suggest that 24S-OHC induces neuronal cell death by necroptosis, a form of programmed necrosis. PMID:21613228

Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis.

PubMed

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

2014-01-01

Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. 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. VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

Genetic traits of avascular necrosis of the femoral head analyzed by array comparative genomic hybridization and real-time polymerase chain reaction.

PubMed

Hwang, Jung-Taek; Baik, Seung-Ho; Choi, Jin-Soo; Lee, Kweon-Haeng; Rhee, Seung-Koo

2011-01-03

In an attempt to observe the genetic traits of avascular necrosis of the femoral head, we analyzed the genomic alterations in blood samples of 18 patients with avascular necrosis of the femoral head (9 idiopathic and 9 alcoholic cases) using the array comparative genomic hybridization method and real-time polymerase chain reaction. Several candidate genes were identified that may induce avascular necrosis of the femoral head, and we investigated their role in the pathomechanism of osteonecrosis of bone. The frequency of each candidate gene over all the categories of avascular necrosis of the femoral head was also calculated by real-time polymerase chain reaction. The highest frequency specific genes in each category were FLJ40296, CYP27C1, and CTDP1. FLJ40296 and CYP27C1 had the highest frequency (55.6%) in the idiopathic category. FLJ40296 had a high frequency (44.4%) in the alcoholic category, but CYP27C1 had a relatively low frequency (33.3%) in the alcoholic category. However, CTDP1 showed a significantly high frequency (55.6%) in the alcoholic category and a low frequency (22.2%) in the idiopathic category. Although we statistically analyzed the frequency of each gene with Fisher's exact test, we could not prove statistical significance due to the small number of samples. Further studies are needed with larger sample numbers. If the causal genes of avascular necrosis of the femoral head are found, they may be used for early detection, prognosis prediction, and genomic treatment of avascular necrosis of the femoral head in the future. Copyright 2011, SLACK Incorporated.

Cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser.

PubMed

Alexsandra da Silva Neto Trajano, Larissa; da Silva, Camila Luna; de Carvalho, Simone Nunes; Cortez, Erika; Mencalha, André Luiz; de Souza da Fonseca, Adenilson; Stumbo, Ana Carolina

2016-07-01

Low-level infrared laser is considered safe and effective for treatment of muscle injuries. However, the mechanism involved on beneficial effects of laser therapy are not understood. The aim was to evaluate cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser at therapeutic fluences. C2C12 myoblast cultures at different (2 and 10 %) fetal bovine serum (FBS) concentrations were exposed to low-level infrared laser (808 nm, 100 mW) at different fluences (10, 35, and 70 J/cm(2)) and evaluated after 24, 48, and 72 h. Cell viability was evaluated by WST-1 assay; reactive oxygen species (ROS), apoptosis, and necrosis were evaluated by flow cytometry. Cell viability was decreased atthe lowest FBS concentration. Laser exposure increased the cell viability in myoblast cultures at 2 % FBS after 48 and 72 h, but no significant increase in ROS was observed. Apoptosis was decreased at the higher fluence and necrosis was increased at lower fluence in myoblast cultures after 24 h of laser exposure at 2 % FBS. No laser-induced alterations were obtained at 10 % FBS. Results show that level of reactive oxygen species is not altered, at least to those evaluated in this study, but low-level infrared laser exposure affects cell viability, apoptosis, and necrosis in myoblast cultures depending on laser fluence and physiologic conditions of cells.

Radiolabeled Rhein as Small-Molecule Necrosis Avid Agents for Imaging of Necrotic Myocardium.

PubMed

Luo, Qi; Jin, Qiaomei; Su, Chang; Zhang, Dongjian; Jiang, Cuihua; Fish, Anne Folta; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

2017-01-17

A rapid and accurate identification of necrotic myocardium is of great importance for diagnosis, risk stratification, clinical decision-making, and prognosis evaluation of myocardial infarction. Here, we explored technetium-99m labeled rhein derivatives for rapid imaging of the necrotic myocardium. Three hydrazinonicotinic acid-linker-rhein (HYNIC-linker-rhein) derivatives were synthesized, and then, these synthetic compounds were labeled with technetium-99m using ethylenediaminediacetic acid (EDDA) and tricine as coligands [ 99m Tc(EDDA)-HYNIC-linker-rhein]. The necrosis avidity of the three 99m Tc-labeled rhein derivatives was tested in a mouse model of ethanol-induced muscular necrosis by gamma counting, histochemical staining, and autoradiography. A lead tracer for visualization of necrotic myocardium was assessed by single photon emission computed tomography/computed tomography (SPECT/CT) imaging in a rat model with reperfused myocardial infarction. The necrosis avidity mechanism of the tracer was explored by DNA binding studies in vitro and blocking experiments in vivo. Results showed that the uptake in necrotic muscles of the three 99m Tc-compounds was higher than that in viable muscles (P < 0.001). Autoradiography and histochemical staining results were consistent with selective uptake of the radiotracer in the necrotic regions. Among the these tracers, 99m Tc(EDDA)-HYNIC-ethylenediamine-rhein [ 99m Tc(EDDA)-HYNIC-2C-rhein] displayed the best distribution profiles for imaging. The necrotic myocardium lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-2C-rhein at 1 h after injection. The necrotic-to-viable myocardium and necrotic myocardium-to-blood uptake ratios of 99m Tc(EDDA)-HYNIC-2C-rhein were 4.79 and 3.02 at 1 h after injection. DNA binding studies suggested HYNIC-linker-rhein bound to DNA through intercalation. The uptake of 99m Tc(EDDA)-HYNIC-2C-rhein in necrotic muscle was significantly blocked by excessive unlabeled rhein, with

Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.

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,more » 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

Fatty acids trigger mitochondrion-dependent necrosis.

PubMed

Rockenfeller, Patrick; Ring, Julia; Muschett, Vera; Beranek, Andreas; Buettner, Sabrina; Carmona-Gutierrez, Didac; Eisenberg, Tobias; Khoury, Chamel; Rechberger, Gerald; Kohlwein, Sepp D; Kroemer, Guido; Madeo, Frank

2010-07-15

Obesity is characterised by lipid accumulation in non-adipose tissues, leading to organ degeneration and a wide range of diseases, including diabetes, heart attack and liver cirrhosis. Free fatty acids (FFA) are believed to be the principal toxic triggers mediating the adverse cellular effects of lipids. Here, we show that various cooking oils used in human nutrition cause cell death in yeast in the presence of a triacylglycerol lipase, mimicking the physiological microenvironment of the small intestine. Combining genetic and cell death assays, we demonstrate that elevated FFA concentrations lead to necrotic cell death, as evidenced by loss of membrane integrity and release of nuclear HMGB1. FFA-mediated necrosis depends on functional mitochondria and leads to the accumulation of reactive oxygen species. We conclude that lipotoxicity is executed via a mitochondrial necrotic pathway, challenging the dogma that the adverse effects of lipid stress are exclusively apoptotic.

Impact of Acellular Dermal Matrix (ADM) Use Under Mastectomy Flap Necrosis on Perioperative Outcomes of Prosthetic Breast Reconstruction.

PubMed

Kim, So Young; Bang, Sa Ik

2017-04-01

There is conflicting data on the potential necrotic complications of acellular dermal matrix (ADM) use in breast reconstruction, and most studies focus on mastectomy flap necrosis as an outcome measure associated with ADM use. The aim of this study was to examine cases with necrotic complications with and without the use of ADM and to investigate whether ADM affected perioperative outcomes in cases with necrotic complications. Patients who experienced mastectomy flap necrosis following mastectomy with tissue expander placement between January 2009 and March 2015 were retrospectively reviewed. The primary outcome was explantation of the expander, and other associated outcomes such as seroma or infection were also recorded. A total of 57 breasts with mastectomy flap necrosis were identified: 32 of which were in the non-ADM group and 25 in the ADM group. The rate of explantation was 28% (7/25) in the ADM group versus 6.3% (2/32) in the non-ADM group, which was significantly different (P = 0.034). The ADM group had a significantly higher rate of "major" infection requiring surgical debridement than the non-ADM group (P = 0.016). Multivariate analysis showed that the use of ADM was trending toward an increasing expander rate with borderline significance (P = 0.05). This study demonstrated that ADM use under mastectomy flap necrosis was a potential risk for explantation of the expander and major infection. Surgeons should be cautious with the use of ADM with devascularized mastectomy skin flaps prone to necrosis. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Surgical management of pancreatic necrosis: A practice management guideline from the Eastern Association for the Surgery of Trauma.

PubMed

Mowery, Nathan T; Bruns, Brandon R; MacNew, Heather G; Agarwal, Suresh; Enniss, Toby M; Khan, Mansoor; Guo, Weidun Alan; Cannon, Jeremy W; Lissauer, Matthew E; Duane, Therese M; Hildreth, Amy N; Pappas, Peter A; Gries, Lynn M; Kaiser, Meghann; Robinson, Bryce R H

2017-08-01

Pancreatic or peripancreatic tissue necrosis confers substantial morbidity and mortality. New modalities have created a wide variation in approaches and timing of interventions for necrotizing pancreatitis. As acute care surgery evolves, its practitioners are increasingly being called upon to manage these complex patients. A systematic review of the MEDLINE database using PubMed was performed. English language articles regarding pancreatic necrosis from 1980 to 2014 were included. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included operative timing, the use of adjuvant therapy and the type of operative repair. Grading of Recommendations, Assessment, Development and Evaluations methodology was applied to question development, outcome prioritization, evidence quality assessments, and recommendation creation. Eighty-eight studies were included and underwent full review. Increasing the time to surgical intervention had an improved outcome in each of the periods evaluated (72 hours, 12-14 days, 30 days) with a significant improvement in outcomes if surgery was delayed 30 days. The use of percutaneous and endoscopic procedures was shown to postpone surgery and potentially be definitive. The use of minimally invasive surgery for debridement and drainage has been shown to be safe and associated with reduced morbidity and mortality. Acute Care Surgeons are uniquely trained to care for those with pancreatic necrosis due their training in critical care and complex surgery with ongoing shock. In adult patients with pancreatic necrosis, we recommend that pancreatic necrosectomy be delayed until at least day 12. During the first 30 days of symptoms with infected necrotic collections, we conditionally recommend surgical debridement only if the patients fail to improve after radiologic or endoscopic drainage. Finally, even with documented infected necrosis, we recommend that patients undergo a step-up approach to

Recent advances in detection and control of infectious hematopoietic necrosis virus in aquaculture

USGS Publications Warehouse

Winton, James R.

1991-01-01

Infectious hematopoietic necrosis (IHN) is one of the most important viral diseases of salmon and trout reared in culture. The disease remains untreatable with avoidance being the only control measure. Much has been learned about the chemical, physical, and serological characteristics of the rhabdovirus causing IHN, but critical gaps exist in our understanding of the biology of the virus in nature. The tools of molecular biology have provided improved methods for detection of pathogens and new strategies for control of viral diseases. This paper reviews several recent improvements in methods for detecting infectious hematopoietic necrosis virus including the application of enzyme-linked immunosorbent assays, development of monoclonal antibodies and DNA probes, and use of the polymerase chain reaction. New strategies for control of IHN through the use of better water treatment, more resistant fish, antiviral drugs or chemicals, and new generation vaccines are discussed.

Susceptibility of cultured juveniles of several marine fish to the sevenband grouper nervous necrosis virus.

PubMed

Tanaka, S; Kuriyama, I; Nakai, T; Miyazaki, T

2003-02-01

Piscine nodaviruses (betanodaviruses) have been tentatively divided into four genotypes (SJNNV, RGNNV, TPNNV and BFNNV) and it is suggested that host specificity is different among these genotypes. In the present study, a betanodavirus [sevenband grouper nervous necrosis virus (SGNNV)] belonging to the redspotted grouper nervous necrosis virus (RGNNV) genotype, to which most betanodaviruses from warm water fish are identified, was evaluated for its pathogenicity to hatchery-reared juveniles of several marine fish species. When challenged with the virus by a bath method (10(5.1) TCID50 mL(-1)), sevenband grouper, Epinephelus septemfasciatus, Japanese flounder, Paralichthys olivaceus, and tiger puffer, Takifugu rubripes, displayed behavioural abnormalities and mortalities with distinct histopathological signs of viral nervous necrosis and heavily immunostained cells were observed in the central nervous tissues and retina. Bath-challenged rock fish, Sebastiscus marmoratus, and a hybrid of sevenband grouper and kelp grouper, E. moara, did not display any behavioural abnormality or mortality during the experimental period, although many fish showed slight signs of viral infection in nerve cells. Kelp grouper and red sea bream, Pagrus major, showed no behavioural abnormality, mortality or immunohistopathological changes after the virus challenge. These results are, in part, consistent with the natural host range of RGNNV, indicating the complexity in the host specificity of betanodaviruses.

Detection of Apoptosis and Necrosis in Normal Human Lung Cells Using 1H NMR Spectroscopy

NASA Astrophysics Data System (ADS)

Shih, Chwen-Ming; Ko, Wun-Chang; Yang, Liang-Yo; Lin, Chien-Ju; Wu, Jui-Sheng; Lo, Tsui-Yun; Wang, Shwu-Huey; Chen, Chien-Tsu

2005-05-01

This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their types and the percentage of cell death were assessed on a flow cytometer. Cadmium (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells, respectively, as revealed by phosphatidylserine externalization on a flow cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm) to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the percentage of apoptosis and strongly and positively correlated with PI staining after Cd treatment (r2 = 0.9868, P < 0.01). In contrast, this ratio only increased slightly within 2-h Hg treatment, and longer Hg exposure failed to produce further increase. Following 2-h Hg exposure, the spectral intensity of choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel tool with a quantitative potential to distinguish apoptosis from necrosis as early as the onset of cell death in normal human lung cells.

Involvement of Lysosome Membrane Permeabilization and Reactive Oxygen Species Production in the Necrosis Induced by Chlamydia muridarum Infection in L929 Cells.

PubMed

Chen, Lixiang; Wang, Cong; Li, Shun; Yu, Xin; Liu, Xue; Ren, Rongrong; Liu, Wenwen; Zhou, Xiaojing; Zhang, Xiaonan; Zhou, Xiaohui

2016-04-28

Chlamydiae, obligate intracellular bacteria, are associated with a variety of human diseases. The chlamydial life cycle undergoes a biphasic development: replicative reticulate bodies (RBs) phase and infectious elementary bodies (EBs) phase. At the end of the chlamydial intracellular life cycle, EBs have to be released to the surrounded cells. Therefore, the interactions between Chlamydiae and cell death pathways could greatly influence the outcomes of Chlamydia infection. However, the underlying molecular mechanisms remain elusive. Here, we investigated host cell death after Chlamydia infection in vitro, in L929 cells, and showed that Chlamydia infection induces cell necrosis, as detected by the propidium iodide (PI)-Annexin V double-staining flow-cytometric assay and Lactate dehydrogenase (LDH) release assay. The production of reactive oxygen species (ROS), an important factor in induction of necrosis, was increased after Chlamydia infection, and inhibition of ROS with specific pharmacological inhibitors, diphenylene iodonium (DPI) or butylated hydroxyanisole (BHA), led to significant suppression of necrosis. Interestingly, live-cell imaging revealed that Chlamydia infection induced lysosome membrane permeabilization (LMP). When an inhibitor upstream of LMP, CA-074-Me, was added to cells, the production of ROS was reduced with concomitant inhibition of necrosis. Taken together, our results indicate that Chlamydia infection elicits the production of ROS, which is dependent on LMP at least partially, followed by induction of host-cell necrosis. To our best knowledge, this is the first live-cell-imaging observation of LMP post Chlamydia infection and report on the link of LMP to ROS to necrosis during Chlamydia infection.

Bilateral breast calciphylaxis in a patient who survived earlier extensive tissue necrosis 5 years previously: A case report.

PubMed

Verstappen, E M J; Maaskant-Braat, A J G; Scheltinga, M R

2018-05-07

Calciphylaxis is a rare condition including patchy dermal necrosis that mostly affects chronic hemodialysis patients. The syndrome usually heralds impending death although patients may survive following a set of measures including an adapted dialysis regimen. The present case is a unique patient who recovered from an earlier episode of upper leg calciphylaxis 5 years previously but developed fatal bilateral breast necrosis. A 69 year old Caucasian woman with a history of atrial fibrillation, hypertension, CVA, hyperparathyroidectomy for secondary hyperparathyroidism and end stage renal disease with hemodialysis recovered in 2012 from extensive symptomatic left upper leg necrosis due to calciphylaxis. In 2017, she developed painful, necrotic ulcers on both breasts, again due to calciphylaxis. She had no history of anticoagulants use but she did use prednisolone 5mg/day. She received adequate wound care, pain medication, antibiotics and dialysis frequency was increased with an addition of sodium thiosulfate. A bilateral ablation was discussed but she decided to stop all treatment following pulmonary aspiration and passed away one week later. Calciphylaxis is a rare diagnosis that should be considered in patients with renal insufficiency developing painful patches of skin necrosis. A multidisciplinary treatment approach including hyperparathyroidectomy, modified hemodialysis and wound treatment is recommended. There is limited evidence for surgical intervention. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[The role of core decompression for the treatment of femoral head avascular necrosis in renal transplant recipients].

PubMed

Zivcić-Cosić, Stela; Stalekar, Hrvoje; Mamula, Mihaela; Miletić, Damir; Orlić, Lidija; Racki, Sanjin; Cicvarić, Tedi

2012-10-01

Avascular bone necrosis is a relatively rare but significant complication in renal transplant recipients because it causes progressive pain and invalidity. It can be the consequence of the action of numerous causative factors, but it is mostly connected to corticosteroid treatment.The underlying pathophysiologic mechanism is a diminished blood flow to the bone leading to necrosis and bone destruction. During the past 25-years period, 570 renal transplantations and five combined kidney and pancreas transplantations were performed in our centre. A part of the patients was lost to follow-up due to the separation of Croatia from the former Republic of Yugoslavia. After transplantation, we revealed aseptic necrosis of the femoral head in five female patients. All patients had a history of treatment with pulse doses of corticosteroids. At transplantation the average age of the patients was 52.2 yrs (range 46 to 62 yrs), and dialytic treatment before transplantation lasted in average 9.2 yrs (range 2.5 to 21.2 yrs). The period between renal transplantation and the development of clinical signs of avascular bone necrosis lasted in average 1.2 yrs (range 0.3 to 2.3 yrs). We will demonstrate our 62-year old female patient with terminal renal failure caused by post-streptococcal glomerulonephritis, who was treated with peritoneal dialysis 2.5 years before renal transplantation. Twenty months before renal transplantation the patient received pulse doses of corticosteroids, together with immunoglobulins and plasmapheresis, for the treatment of an acute polyradiculoneuritis Guillaine Barré. After transplantation a standard immunosuppressive protocol was applied which included tacrolimus, mycophenolate mofetil, corticosteroids and induction with basiliximab. Four months after transplantation the patient started to feel pain in the right hip after longer standing, in addition to the earlier long-lasting problems caused by bilateral coxarthrosis. The pelvic radiograph showed

Cationic nanocarriers induce cell necrosis through impairment of Na+/K+-ATPase and cause subsequent inflammatory response

PubMed Central

Wei, Xiawei; Shao, Bin; He, Zhiyao; Ye, Tinghong; Luo, Min; Sang, Yaxiong; Liang, Xiao; Wang, Wei; Luo, Shuntao; Yang, Shengyong; Zhang, Shuang; Gong, Changyang; Gou, Maling; Deng, Hongxing; Zhao, Yinglan; Yang, Hanshuo; Deng, Senyi; Zhao, Chengjian; Yang, Li; Qian, Zhiyong; Li, Jiong; Sun, Xun; Han, Jiahuai; Jiang, Chengyu; Wu, Min; Zhang, Zhirong

2015-01-01

Nanocarriers with positive surface charges are known for their toxicity which has limited their clinical applications. The mechanism underlying their toxicity, such as the induction of inflammatory response, remains largely unknown. In the present study we found that injection of cationic nanocarriers, including cationic liposomes, PEI, and chitosan, led to the rapid appearance of necrotic cells. Cell necrosis induced by cationic nanocarriers is dependent on their positive surface charges, but does not require RIP1 and Mlkl. Instead, intracellular Na+ overload was found to accompany the cell death. Depletion of Na+ in culture medium or pretreatment of cells with the Na+/K+-ATPase cation-binding site inhibitor ouabain, protected cells from cell necrosis. Moreover, treatment with cationic nanocarriers inhibited Na+/K+-ATPase activity both in vitro and in vivo. The computational simulation showed that cationic carriers could interact with cation-binding site of Na+/K+-ATPase. Mice pretreated with a small dose of ouabain showed improved survival after injection of a lethal dose of cationic nanocarriers. Further analyses suggest that cell necrosis induced by cationic nanocarriers and the resulting leakage of mitochondrial DNA could trigger severe inflammation in vivo, which is mediated by a pathway involving TLR9 and MyD88 signaling. Taken together, our results reveal a novel mechanism whereby cationic nanocarriers induce acute cell necrosis through the interaction with Na+/K+-ATPase, with the subsequent exposure of mitochondrial damage-associated molecular patterns as a key event that mediates the inflammatory responses. Our study has important implications for evaluating the biocompatibility of nanocarriers and designing better and safer ones for drug delivery. PMID:25613571

Towards a 'human-like' model of tuberculosis: intranasal inoculation of LPS induces intragranulomatous lung necrosis in mice infected aerogenically with Mycobacterium tuberculosis.

PubMed

Cardona, P J; Llatjós, R; Gordillo, S; Díaz, J; Viñado, B; Ariza, A; Ausina, V

2001-01-01

It is well known that one of the differences between murine and human tuberculosis is the lack of intragranulomatous necrosis in the former. The aim of this study was to create a feasible and reproducible model of an experimental model of murine tuberculosis in which this necrosis should be present. Considering the Shwartzman reaction as a possible explanation for intragranulomatous necrosis in human tuberculosis, C57Bl/6 mice, infected aerogenically with a virulent strain of Mycobacterium tuberculosis, were intranasally inoculated with lipopolysaccharide (LPS) on day 19 postinfection (p.i.). Twenty-four hours later, neutrophils infiltrated the lung parenchyma in a significant level, and 10 days after necrosis could be detected in the centres of primary granulomas, that showed scanty macrophages and large amounts of collagen on an eosinophilic background. On the other hand, a significant decrease in the concentration of colony forming units (CFU) could be appreciated 24 h after the LPS inoculation. Afterwards, nonbronchogenic spreading of granulomas increased and higher levels of interferon (IFN)-gamma mRNA were detected. These results lend support to the Shwartzman reaction as the origin of the intragranulomatous necrosis in the M. tuberculosis infection, and provides a useful tool to improve experimental murine models in tuberculosis.

Avascular necrosis of the femoral head in patients treated for leukaemia. Assessment of the need for a diagnostic protocol.

PubMed

Alguacil Pinel, J; Vila Vives, P; Salom Taverner, M

To evaluate the incidence of avascular necrosis of the hip in leukaemia patients treated in our hospital with high doses of corticosteroids in order to evaluate the necessity for an early detection protocol. Observational-descriptive and retrospective study from 2005 to 2016 of 253 patients diagnosed with paediatric leukaemia. Patients with musculoskeletal pathology were identified and patients with avascular necrosis were analysed. A total of 26 patients (10%) had musculoskeletal symptoms. Three patients with avascular necrosis (1.2%) were analysed. One girl, 7 years old, was treated conservatively with traction - suspension and discharge. Two boys, an 11 and a 15.4 year-old,who developed graft-versus-host disease secondary to bone marrow transplantation, and whose treatment included high doses of corticosteroids, developed avascular necrosis of the hip. One was treated with bisphosphonates and forage and the other ended up with a total hip arthroplasty. The occurrence of musculoskeletal symptoms during the treatment of leukaemia is different according to the bibliographic series (0.43 -12.6%). Some authors observe an increased risk in female patients between the ages of 10 and 17. A retrospective study reveals that there is a delay of 3.9 months in the diagnosis of CAP since the onset of pain. Other authors relate NAV to loading joints, age and high doses of corticosteroids. Based on the low incidence of avascular necrosis of the hip in our 14-year-old population treated for leukaemia, the creation of diagnostic protocols seems not to be necessary. However, close monitoring of patients with potential risk factors recognized in the literature, is advisable. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

The acquisition of molecular determinants involved in potato virus Y necrosis capacity leads to fitness reduction in tobacco plants.

PubMed

Rolland, Mathieu; Kerlan, Camille; Jacquot, Emmanuel

2009-01-01

The prevalence of necrotic potato virus Y (PVY) in natural populations could reflect increased fitness of necrotic isolates. In this paper, the effects of the acquisition of molecular determinants (A/G(2213) and A/C(2271)) involved in necrosis capacity on both the number of progeny produced and the competitiveness of PVY were characterized. The relationship between necrosis and fitness was tested using (i) Nicotiana tabacum cv. Xanthi and Nicotiana clevelandii, (ii) necrotic PVY(N)-605 and non-necrotic PVY(O)-139 isolates, (iii) single-mutated (PVY(KR) and PVY(ED)) and double-mutated (PVY(KRED)) versions of PVY(N)-605 and (iv) three quantitative PCR assays specific for nt A(2213), G(2213) and A(2271) of the PVY genome. The data demonstrated effects of both the genetic background and nt 2213 and 2271 on the fitness of PVY. Quantification of PVY RNA in singly infected plants revealed that both the PVY(N)-605 genetic background and the acquisition of necrotic capacity resulted in a decrease in the number of progeny produced. Competition experiments revealed that the genetic background of PVY(N) had a positive impact on competitiveness. In contrast, nucleotides involved in necrotic properties were associated with decreased fitness. Finally, in the host that did not respond to infection with necrosis, the benefit associated with the PVY(N)-605 genetic background was higher than the cost associated with the acquisition of molecular determinants involved in necrosis capacity. The opposite result was obtained in the host responding to the infection with necrosis. These results indicate that the emergence of necrotic isolates from a non-necrotic population is unlikely in tobacco.

Effects of octenidine mouth rinse on apoptosis and necrosis of human fibroblasts and epithelial cells - an in vitro study.

PubMed

Schmidt, J; Zyba, V; Jung, K; Rinke, S; Haak, R; Mausberg, R F; Ziebolz, D

2018-04-01

This study aimed at comparing the cytotoxicity of a new octenidine mouth rinse (MR) on gingival fibroblasts and epithelial cells using different established MRs. Octenidol (OCT), Chlorhexidine 0.2% (CHX), Meridol (MER), Oral B (OB), and control (PBS only) were used. Human primary gingival fibroblasts (HGFIBs) and human primary nasal epithelial cells (HNEPCs) were cultivated in cell-specific media (2 × 10 5 cells/well) and treated with a MR or PBS for 1, 5, and 15 min. All tests were performed in duplicate and repeated 12 times. The apoptosis and necrosis were determined using a Caspase-3/7 assay and LDH assay, respectively. The data were analyzed using two-way analysis of variance with subsequent Mann-Whitney U-test. No significant differences could be found between the incubation times of the MR, neither for apoptosis nor necrosis (p > 0.05). Regarding apoptosis of HGFIBs, MRs had no influence at all. In HNEPCs, OCT induced relevantly lower apoptosis than CHX (p = 0.01). Considering necrosis, MER showed the lowest numbers of necrotic HGFIBs and HNEPCs, whereas OB induced the highest number of necrotic cells. The differences between both MR were statistically relevant (p < 0.01). OCT did neither differ from the other MRs nor from the control (PBS) in induction of necrosis in both cell types. In conclusion, the slightly negative effect of OCT considering apoptosis and necrosis of HGFIBs and HNEPCs is nearly the same or even lower compared to the established MRs included in this study. The results confirm that OCT is a potential alternative to CHX.