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Sample records for acute tubular necrosis

  1. Microvascular inflammation and acute tubular necrosis are major histologic features of hantavirus nephropathy.

    PubMed

    Gnemmi, Viviane; Verine, Jérôme; Vrigneaud, Laurence; Glowacki, François; Ratsimbazafy, Anderson; Copin, Marie-Christine; Dewilde, Anny; Buob, David

    2015-06-01

    Hantavirus nephropathy (HVN) is an uncommon etiology of acute renal failure due to hantavirus infection. Pathological features suggestive of HVN historically reported are medullary interstitial hemorrhages in a background of acute interstitial nephritis (AIN). However, interstitial hemorrhages may be lacking because of medullary sampling error. This emphasizes that other pathological criteria may be of interest. We performed a retrospective clinicopathological study of 17 serologically proven HVN cases with renal biopsy from 2 nephrology centers in northern France. Histologic analysis was completed by immunohistochemistry with anti-CD3, anti-CD68, and anti-CD34 antibodies. Three control groups were not related to hantavirus infection: acute tubular necrosis (ATN) of ischemic or toxic etiology and AIN were used for comparison. Renal biopsy analysis showed that almost all HVN cases with medullary sampling (9/10) displayed interstitial hemorrhages, whereas focal hemorrhages were detected in 2 of the 7 "cortex-only" specimens. ATN was common, as it was present in 15 (88.2%) of 17 HVN cases. By contrast, interstitial inflammation was scarce with no inflammation or only slight inflammation, representing 15 (88.2%) of 17 cases. Moreover, HVN showed inflammation of renal microvessels with cortical peritubular capillaritis and medullary vasa recta inflammation; peritubular capillaritis was significantly higher in HVN after comparison with ischemic and toxic ATN controls (P = .0001 and P = .003, respectively), but not with AIN controls. Immunohistochemical studies highlighted the involvement of T cells and macrophages in renal microvascular inflammation related to HVN. Our study showed that microvascular inflammation, especially cortical peritubular capillaritis, and ATN are important histologic features of HVN. PMID:25791582

  2. BIOPSY PROVEN ACUTE TUBULAR NECROSIS DUE TO RHABDOMYOLYSIS IN A DENGUE FEVER PATIENT: A CASE REPORT AND REVIEW OF LITERATURE

    PubMed Central

    Repizo, Liliany P.; Malheiros, Denise M.; Yu, Luis; Barros, Rui T.; Burdmann, Emmanuel A.

    2014-01-01

    Renal histology results are very scarce in dengue-associated rhabdomyolysis patients developing acute kidney injury (AKI). We report a case of dengue fever-induced AKI associated to rhabdomyolysis with a renal biopsy showing acute tubular necrosis (ATN) and renal deposition of myoglobin. A 28-year-old patient who presented dengue fever (DF) complicated by severe AKI and rhabdomyolysis is described. The patient required hemodialysis for three weeks. A renal biopsy revealed ATN with positive staining for myoglobin in the renal tubuli. The patient was discharged with recovered renal function. In conclusion, this case report described a biopsy proven ATN associated to DF-induced rhabdomyolysis, in which renal deposition of myoglobin was demonstrated. We suggest that serum creatine phosphokinase should be monitored in DF patients to allow for an early diagnosis of rhabdomyolysis and the institution of renal protective measures. PMID:24553615

  3. Acute tubular necrosis (ATN) presenting with an unusually prolonged period of marked polyuria heralded by an abrupt oliguric phase

    PubMed Central

    Ramoutar, Virin; Landa, Cristian; James, Leighton R

    2014-01-01

    A 50-year-old African-American man presented with acute tubular necrosis (ATN) secondary to hypotension from non-typhoid Salmonella gastroenteritis and bacteraemia. The oliguric phase lasted only 24 h followed by prolonged polyuria for 20 days, with urine output in excess of 16 L/day at maximum. As indexed in PubMed this is only the second published case of this nature since 1974, in which an abrupt oliguric phase of 24 h or less heralded prolonged polyuria in ATN. The diagnosis is challenging as fractional excretion of sodium early in the clinical course and rapid normalisation of serum creatinine with intravenous fluids (IVF) may point towards prerenal azotaemia resulting in a premature discharge from hospital. Patients with an abrupt oliguric phase may suffer a secondary renal insult from the profound fluid loss that is to follow and may need inpatient monitoring with supplemental IVF to prevent deleterious outcomes. PMID:25150229

  4. Acute tubular necrosis

    MedlinePlus

    ... in the following cases: Decreased mental status Fluid overload Increased potassium level Pericarditis Removal of toxins that ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  5. Acute tubular necrosis

    MedlinePlus

    ... is often caused by a lack of blood flow and oxygen to the kidney tissues (ischemia of the kidneys). ... treating conditions that can lead to decreased blood flow as well as decreased oxygen to the kidneys can reduce the risk for ...

  6. Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis

    PubMed Central

    Kim, Kyung Min; Sung, Kyoung; Yang, Hea Koung; Kim, Seong Heon; Kim, Hye Young; Ban, Gil Ho; Park, Su Eun; Lee, Hyoung Doo

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature. PMID:27186222

  7. [Acute retinal necrosis].

    PubMed

    Lucke, K; Reinking, U; el-Hifnawi, E; Dennin, R H; Laqua, H

    1988-12-01

    The authors report on three patients with acute retinal necrosis who were treated with the virostatic agent Acyclovir and who underwent vitreoretinal surgery with silicone oil filling for total retinal detachment. In two eyes the retina was reattached, but useful vision was only preserved in one patient. Titers from blood and the vitreous, as well as microscopic findings in retinal biopsies, support the view that the necrosis is caused by a herpes simplex virus infection. After therapy with Acyclovir was instituted no further progression on the necrosis was observed. However, the development of retinal detachment could not be prevented. Early diagnosis and antiviral therapy are essential to improve the otherwise poor prognosis in this rare syndrome. PMID:3221657

  8. Black Anal Canal: Acute Necrosis

    PubMed Central

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

    2016-01-01

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

  9. 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

  10. Acute oesophageal necrosis (black oesophagus).

    PubMed

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

    2016-03-01

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

  11. Epidermal growth factor attenuates tubular necrosis following mercuric chloride damage by regeneration of indigenous, not bone marrow-derived cells

    PubMed Central

    Yen, Tzung-Hai; Alison, Malcolm R; Goodlad, Robert A; Otto, William R; Jeffery, Rosemary; Cook, H Terence; Wright, Nicholas A; Poulsom, Richard

    2015-01-01

    To assess effects of epidermal growth factor (EGF) and pegylated granulocyte colony-stimulating factor (P-GCSF; pegfilgrastim) administration on the cellular origin of renal tubular epithelium regenerating after acute kidney injury initiated by mercuric chloride (HgCl2). Female mice were irradiated and male whole bone marrow (BM) was transplanted into them. Six weeks later recipient mice were assigned to one of eight groups: control, P-GCSF+, EGF+, P-GCSF+EGF+, HgCl2, HgCl2+P-GCSF+, HgCl2+EGF+ and HgCl2+P-GCSF+EGF+. Following HgCl2, injection tubular injury scores increased and serum urea nitrogen levels reached uraemia after 3 days, but EGF-treated groups were resistant to this acute kidney injury. A four-in-one analytical technique for identification of cellular origin, tubular phenotype, basement membrane and S-phase status revealed that BM contributed 1% of proximal tubular epithelium in undamaged kidneys and 3% after HgCl2 damage, with no effects of exogenous EGF or P-GCSF. Only 0.5% proximal tubular cells were seen in S-phase in the undamaged group kidneys; this increased to 7–8% after HgCl2 damage and to 15% after addition of EGF. Most of the regenerating tubular epithelium originated from the indigenous pool. BM contributed up to 6.6% of the proximal tubular cells in S-phase after HgCl2 damage, but only to 3.3% after additional EGF. EGF administration attenuated tubular necrosis following HgCl2 damage, and the major cause of this protective effect was division of indigenous cells, whereas BM-derived cells were less responsive. P-GCSF did not influence damage or regeneration. PMID:25389045

  12. Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury

    PubMed Central

    Sancho-Martínez, Sandra M.; López-Novoa, José M.; López-Hernández, Francisco J.

    2015-01-01

    The histological substrate of many forms of intrinsic acute kidney injury (AKI) has been classically attributed to tubular necrosis. However, more recent studies indicate that necrosis is not the main form of cell death in AKI and that other forms such as apoptosis, regulated necrosis (i.e. necroptosis and parthanatos), autophagic cell death and mitotic catastrophe, also participate in AKI and that their contribution depends on the cause and stage of AKI. Herein, we briefly summarize the main characteristics of the major types of cell death and we also critically review the existing evidence on the occurrence of different types of cell death reported in the most common experimental models of AKI and human specimens. We also discuss the pathophysiological mechanisms linking tubule epithelial cell death with reduced glomerular filtration, azotaemia and hydroelectrolytic imbalance. For instance, special relevance is given to the analysis of the inflammatory component of some forms of cell death over that of others, as an important and differential pathophysiological determinant. Finally, known molecular mechanisms and signalling pathways involved in each cell death type pose appropriate targets to specifically prevent or reverse AKI, provided that further knowledge of their participation and repercussion in each AKI syndrome is progressively increased in the near future. PMID:26413280

  13. Acute tubular nephropathy in a patient with acute HIV infection: review of the literature.

    PubMed

    Ananworanich, Jintanat; Datta, Anandita A; Fletcher, James Lk; Townamchai, Natavudh; Chomchey, Nitiya; Kroon, Eugene; Sereti, Irini; Valcour, Victor; Kim, Jerome H

    2014-01-01

    We report a 57-year old man with diabetes mellitus and hypertension who presented with acute HIV infection. Routine blood tests showed an elevated blood urea nitrogen and creatinine. Renal biopsy showed acute tubular nephropathy, which has not been reported to occur during acute HIV infection, in the absence of rhabdomyolysis or multiple organ system failure. Antiretroviral therapy was initiated. His renal failure gradually resolved without further intervention. At one year of follow-up his HIV RNA was undetectable, and his renal function was normal. The case illustrates a rare manifestation of acute HIV infection - acute renal failure - in an older man with diabetes and hypertension. In this setting acute kidney injury might mistakenly have been attributed to his chronic comorbidities, and this case supports early HIV-1 testing in the setting of a high index of suspicion. PMID:25745498

  14. Contemporary management of infected necrosis complicating severe acute pancreatitis

    PubMed Central

    Jamdar, Saurabh; Siriwardena, Ajith K

    2006-01-01

    Pancreatic necrosis complicating severe acute pancreatitis is a challenging scenario in contemporary critical care practice; it requires multidisciplinary care in a setting where there is a relatively limited evidence base to support decision making. This commentary provides a concise overview of current management of patients with infected necrosis, focusing on detection, the role of pharmacologic intervention, and the timing and nature of surgical interventions. Fine-needle aspiration of necrosis remains the mainstay for establishment of infection. Pharmacological intervention includes antibiotic therapy as an adjunct to surgical debridement/drainage and, more recently, drotrecogin alfa. Specific concerns remain regarding the suitability of drotrecogin alfa in this setting. Early surgical intervention is unhelpful; surgery is indicated when there is strong evidence for infection of necrotic tissue, with the current trend being toward 'less drastic' surgical interventions. PMID:16356213

  15. Clinical Manifestation of Self-Limiting Acute Retinal Necrosis

    PubMed Central

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

    2014-01-01

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

  16. Emerging concepts in the management of acute retinal necrosis.

    PubMed

    Wong, Robert William; Jumper, J Michael; McDonald, H Richard; Johnson, Robert N; Fu, Arthur; Lujan, Brandon J; Cunningham, Emmett T

    2013-05-01

    Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon condition caused by infection of the retina by one of the herpes family of viruses, most typically varicella zoster virus or herpes simplex virus and less commonly cytomegalovirus. Clinical diagnosis can be challenging and is often aided by PCR-based analysis of ocular fluids. Treatment typically involves extended use of one or more antiviral agents. Long term retinal detachment risk is high. We review the literature on ARN and present an approach to the diagnosis and management of this serious condition. PMID:23235944

  17. 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

  18. Antiviral selection in the management of acute retinal necrosis

    PubMed Central

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

    2010-01-01

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

  19. Gallbladder torsion with acute cholecystitis and gross necrosis

    PubMed Central

    Alkhalili, Eyas; Bencsath, Kalman

    2014-01-01

    A 92-year-old woman presented to the emergency department with a 2-week history of worsening right-sided abdominal pain. On examination she had right mid-abdominal tenderness. Laboratory studies demonstrated leukocytosis with normal liver function tests. A CT of the abdomen was remarkable for a large fluid collection in the right abdomen and no discernible gallbladder in the gallbladder fossa. An ultrasound confirmed the suspicion of a distended, floating gallbladder. The patient was taken to the operating room for laparoscopic cholecystectomy. The gallbladder was found to have volvulised in a counter -clockwise manner around its pedicle, with gross necrosis of the gallbladder. She underwent laparoscopic cholecystectomy. Pathological examination revealed acute necrotising calculus cholecystitis. PMID:24862426

  20. Acute retinal necrosis secondary to herpes simplex virus type 2 with preexisting chorioretinal scarring.

    PubMed

    Moesen, Ingemarie; Khemka, Sneh; Ayliffe, William

    2008-01-01

    Acute retinal necrosis in children is a devastating disease that requires early diagnosis and treatment. The authors describe a rarely reported case of bilateral acute retinal necrosis in a child caused by neonatal herpes simplex virus type 2, where the presence of previous chorioretinal scarring made diagnosis challenging. PMID:18286969

  1. Expression of Tumor Necrosis Factor in Human Acute Cardiac Rejection

    PubMed Central

    Arbustini, Eloisa; Grasso, Maurizia; Diegoli, Marta; Bramerio, Manuela; Foglieni, Andrea Scotti; Albertario, Marco; Martinelli, Luigi; Gavazzi, Antonello; Goggi, Claudio; Campana, Carlo; Vigano, Mario

    1991-01-01

    The authors performed an immunohistochemical study on expression of tumor necrosis factor alpha (TNFα) in endomyocardial biopsies from human cardiac allografts. TNFα immunoreactivity was found in 45% biopsies with mild acute rejection, in 83% biopsies with focal moderate rejection, in 80% biopsies with diffuse moderate rejection. Biopsies with absent rejection did not show immunoreactive cells. In mild rejection, positive cells were few and scanty monocytes and macrophages (MAC-387 and LN5 positive cells) and T lymphocytes (UCHL-1/CD45 RO positive cells) (up to 20% of all infiltrating cells). Expression of major histocompatibility complex (MHC) class II antigens on infiltrating and endothelial cells occurred earlier and independent of TNFα reactivity. Number of immunoreactive cells increased in moderate rejection (up to 50%). Immunoreactivity was also present in nonpigmented macrophages in part of the biopsies with resolving rejection (45%). The authors conclude that TNFα is expressed in acute cardiac rejection by immunologically activated inflammatory cells. Immunoreactive cells increase in number with increasing severity of the reaction. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:1928295

  2. Quantitation of Acute Necrosis After Experimental Myocardial Infarction

    PubMed Central

    Yeap, Xin-Yi; Dehn, Shirley; Adelman, Jeremy; Lipsitz, Jeremy; Thorp, Edward B.

    2016-01-01

    Myocardial infarction (MI) is death and necrosis of myocardial tissue secondary to ischemia. MI is associated with adverse cardiac remodeling, progressive heart chamber dilation, ventricular wall thinning, and loss of cardiac function. Myocardial necrosis can be experimentally induced in rodents to simulate human MI by surgical occlusion of coronary arteries. When induced in knockout or transgenic mice, this model is useful for the identification of molecular modulators of cell death, cardiac remodeling, and preclinical therapeutic potential. Herein we outline in tandem, methods for microsurgical ligation of the left anterior descending artery followed by quantitation of myocardial necrosis. Necrosis is quantified after staining the heart with triphenyltetrazolium chloride. PMID:23733573

  3. Use of drug therapy to manage acute cutaneous necrosis of the skin.

    PubMed

    Wallace, Jill S; Hall, John C

    2010-04-01

    Acute cutaneous necrosis is defined as a sudden onset of gangrenous skin changes in the skin, associated with significant morbidity and mortality. The following diseases are included in this discussion: coumadin necrosis, heparin necrosis, brown recluse spider bite, necrotizing fasciitis, vasculitis, pyoderma gangrenosum, calciphylaxis, clotting abnormalities and embolic phenomena. The importance of early diagnosis, early distinction and early drug therapy or drug withdrawal must match the diagnosis for maximal preservation of the skin and underlying tissue. PMID:20514791

  4. Tumor necrosis factor-α induces a biphasic change in claudin-2 expression in tubular epithelial cells: role in barrier functions.

    PubMed

    Amoozadeh, Yasaman; Dan, Qinghong; Xiao, Jenny; Waheed, Faiza; Szászi, Katalin

    2015-07-01

    The inflammatory cytokine tumor necrosis factor-α (TNF-α) is a pathogenic factor in acute and chronic kidney disease. TNF-α is known to alter expression of epithelial tight junction (TJ) proteins; however, the underlying mechanisms and the impact of this effect on epithelial functions remain poorly defined. Here we describe a novel biphasic effect of TNF-α on TJ protein expression. In LLC-PK1 tubular cells, short-term (1-6 h) TNF-α treatment selectively elevated the expression of the channel-forming TJ protein claudin-2. In contrast, prolonged (>8 h) TNF-α treatment caused a marked downregulation in claudin-2 and an increase in claudin-1, -4, and -7. The early increase and the late decrease in claudin-2 expression involved distinct mechanisms. TNF-α slowed claudin-2 degradation through ERK, causing the early increase. This increase was also mediated by the EGF receptor and RhoA and Rho kinase. In contrast, prolonged TNF-α treatment reduced claudin-2 mRNA levels and promoter activity independent from these signaling pathways. Electric Cell-substrate Impedance Sensing measurements revealed that TNF-α also exerted a biphasic effect on transepithelial resistance (TER) with an initial decrease and a late increase. Thus there was a good temporal correlation between TNF-α-induced claudin-2 protein and TER changes. Indeed, silencing experiments showed that the late TER increase was at least in part caused by reduced claudin-2 expression. Surprisingly, however, claudin-2 silencing did not prevent the early TER drop. Taken together, the TNF-α-induced changes in claudin-2 levels might contribute to TER changes and could also play a role in newly described functions of claudin-2 such as proliferation regulation. PMID:25948735

  5. Tumor necrosis factor-α induces a biphasic change in claudin-2 expression in tubular epithelial cells: role in barrier functions

    PubMed Central

    Amoozadeh, Yasaman; Dan, Qinghong; Xiao, Jenny; Waheed, Faiza

    2015-01-01

    The inflammatory cytokine tumor necrosis factor-α (TNF-α) is a pathogenic factor in acute and chronic kidney disease. TNF-α is known to alter expression of epithelial tight junction (TJ) proteins; however, the underlying mechanisms and the impact of this effect on epithelial functions remain poorly defined. Here we describe a novel biphasic effect of TNF-α on TJ protein expression. In LLC-PK1 tubular cells, short-term (1–6 h) TNF-α treatment selectively elevated the expression of the channel-forming TJ protein claudin-2. In contrast, prolonged (>8 h) TNF-α treatment caused a marked downregulation in claudin-2 and an increase in claudin-1, -4, and -7. The early increase and the late decrease in claudin-2 expression involved distinct mechanisms. TNF-α slowed claudin-2 degradation through ERK, causing the early increase. This increase was also mediated by the EGF receptor and RhoA and Rho kinase. In contrast, prolonged TNF-α treatment reduced claudin-2 mRNA levels and promoter activity independent from these signaling pathways. Electric Cell-substrate Impedance Sensing measurements revealed that TNF-α also exerted a biphasic effect on transepithelial resistance (TER) with an initial decrease and a late increase. Thus there was a good temporal correlation between TNF-α-induced claudin-2 protein and TER changes. Indeed, silencing experiments showed that the late TER increase was at least in part caused by reduced claudin-2 expression. Surprisingly, however, claudin-2 silencing did not prevent the early TER drop. Taken together, the TNF-α-induced changes in claudin-2 levels might contribute to TER changes and could also play a role in newly described functions of claudin-2 such as proliferation regulation. PMID:25948735

  6. Coagulopathy and encephalopathy in a dog with acute hepatic necrosis.

    PubMed

    Strombeck, D R; Krum, S; Rogers, Q

    1976-10-15

    Disseminated intravascular coagulation developed secondary to hepatic necrosis in a 5-year-old Saint Bernard. Although the coagulopathy responded to treatment with heparin, the dog died from the combined effects of gastric hemorrhage and encephalopathy, both of which are complications of hepatic necrosis. PMID:977448

  7. Alteration of Fatty Acid Oxidation in Tubular Epithelial Cells: From Acute Kidney Injury to Renal Fibrogenesis

    PubMed Central

    Simon, Noémie; Hertig, Alexandre

    2015-01-01

    Renal proximal tubular cells are the most energy-demanding cells in the body. The ATP that they use is mostly produced in their mitochondrial and peroxisomal compartments, by the oxidation of fatty acids. When those cells are placed under a biological stress, such as a transient hypoxia, fatty acid oxidation (FAO) is shut down for a period of time that outlasts injury, and carbohydrate oxidation does not take over. Facing those metabolic constraints, surviving tubular epithelial cells exhibit a phenotypic switch that includes cytoskeletal rearrangement and production of extracellular matrix proteins, most probably contributing to acute kidney injury-induced renal fibrogenesis, thence to the development of chronic kidney disease. Here, we review experimental evidence that dysregulation of FAO profoundly affects the fate of tubular epithelial cells, by promoting epithelial-to-mesenchymal transition, inflammation, and eventually interstitial fibrosis. Restoring physiological production of energy is undoubtedly a possible therapeutic approach to unlock the mesenchymal reprograming of tubular epithelial cells in the kidney. In this respect, the benefit of the use of fibrates is uncertain, but new drugs that could specifically target this metabolic pathway, and, hopefully, attenuate renal fibrosis merit future research. PMID:26301223

  8. Renal tubular Notch signaling triggers a prosenescent state after acute kidney injury.

    PubMed

    Sörensen-Zender, Inga; Rong, Song; Susnik, Nathan; Zender, Steffen; Pennekamp, Petra; Melk, Anette; Haller, Hermann; Schmitt, Roland

    2014-04-15

    The aging kidney has a diminished regenerative potential and an increased tendency to develop tubular atrophy and fibrosis after acute injury. In this study, we found that activation of tubular epithelial Notch1 signaling was prolonged in the aging kidney after ischemia/reperfusion (IR) damage. To analyze the consequences of sustained Notch activation, we generated mice with conditional inducible expression of Notch1 intracellular domain (NICD) in proximal tubules. NICD kidneys were analyzed 1 and 4 wk after renal IR. Conditional NICD expression was associated with aggravated tubular damage, a fibrotic phenotype, and the expression of cellular senescence markers p21 and p16(INK4a). In wild-type mice pharmacological inhibition of Notch using the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) improved tubulo-interstitial damage and antagonized the prosenescent pathway activation after IR. In vitro, activation of Notch signaling with delta-like-ligand-4 caused prosenescent changes in tubular cells while inhibition with DAPT attenuated these changes. In conclusion, our data suggest that sustained epithelial Notch activation after IR might contribute to the inferior outcome of old kidneys after injury. Sustained epithelial activation of Notch is associated with a prosenescent phenotype and maladaptive repair. PMID:24573392

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

    PubMed

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

    2014-05-01

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

  10. Tumor Necrosis Factor Alpha Promoter Polymorphism and Severity of Acute Kidney Injury

    PubMed Central

    Susantitaphong, Paweena; Perianayagam, Mary C.; Tighiouart, Hocine; Liangos, Orfeas; Bonventre, Joseph V.; Jaber, Bertrand L.

    2016-01-01

    Background Tumor necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the pathobiology of acute kidney injury (AKI). Methods We explored the association of a functional polymorphism in the promoter region (rs1800629) of the TNFA gene with severity of AKI, as defined by level of glomerular filtration (serum cystatin C and creatinine) and tubular injury (urinary NAG, KIM-1, α-GST, and π-GST) markers, in 262 hospitalized adults. Results In unadjusted analyses, compared with the GG genotype, the TNFA GA and AA genotype groups tended to have higher enrollment (p = 0.08), peak (p = 0.004), and discharge (p = 0.004) serum creatinine levels, and the AA genotype tended to have a higher enrollment serum cystatin C level (p = 0.04). Compared with the GG genotype, the TNFA GA and AA genotype groups tended to have a higher urinary KIM-1 level (p = 0.03), and the AA genotype group tended to have a higher urinary π-GST level (p = 0.03). After adjustment for sex, race, age, baseline estimated glomerular filtration rate, sepsis, and dialysis requirement, compared with the GG genotype, the TNFA minor A-allele group had a higher peak serum creatinine of 1.03 mg/dl (0.43, 1.63; p = 0.001) and a higher urinary KIM-1 (relative ratio: 1.73; 95% CI: 1.16, 2.59; p = 0.008). The TNFA minor A-allele group also had a higher Multiple Organ Failure score of 0.26 (95% CI: 0.03, 0.49; p = 0.024) after adjustment for sex, race, age, and sepsis. Conclusions The TNFA rs1800629 gene polymorphism is associated with markers of kidney disease severity and distant organ dysfunction among patients with AKI. Larger studies are needed to confirm these relationships. PMID:23796916

  11. Ablation of proximal tubular suppressor of cytokine signaling 3 enhances tubular cell cycling and modifies macrophage phenotype during acute kidney injury.

    PubMed

    Susnik, Nathan; Sörensen-Zender, Inga; Rong, Song; von Vietinghoff, Sibylle; Lu, Xia; Rubera, Isabelle; Tauc, Michel; Falk, Christine S; Alexander, Warren S; Melk, Anette; Haller, Herrmann; Schmitt, Roland

    2014-06-01

    Suppressor of cytokine signaling 3 (SOCS-3) is an important intracellular negative regulator of several signaling pathways. We found that SOCS-3 is highly expressed in renal proximal tubules during acute kidney injury. To test the impact of this, conditional proximal tubular knockout mice (SOCS-3(sglt2Δ/sglt2Δ)) were created. These mice had better kidney function than their wild-type counterparts in aristolochic acid nephropathy and after ischemia/reperfusion injury. Kidneys of these knockout mice showed significantly more proximal tubular cell proliferation during the repair phase. A direct effect of SOCS-3 on tubular cell cycling was demonstrated by in vitro experiments showing a JAK/STAT pathway-dependent antimitotic effect of SOCS-3. Furthermore, acute damaged kidneys of the knockout mice contained increased numbers of F4/80(+) cells. Phenotypic analysis of these F4/80(+) cells indicated a polarization from classically activated to alternatively activated macrophages. In vitro, SOCS-3-overexpressing renal epithelial cells directly induced classical activation in cocultured macrophages, supporting the observed in vivo phenomenon. Thus, upregulation of SOCS-3 in stressed proximal tubules plays an important role during acute kidney injury by inhibition of reparative proliferation and by modulation of the macrophage phenotype. Antagonizing SOCS-3 could have therapeutic potential for acute kidney injury. PMID:24402091

  12. [Acute hemorrhagic necrosis of the breast following treatment with Cumarin].

    PubMed

    Lüchtrath, H; Walkowsky, A

    1983-08-01

    A case of hemorrhagic necrosis of the breast is reported in a thirty-four year old woman who received Cumarin treatment for deep leg vein thrombosis and pulmonary embolism. It was necessary to remove the breast. The microscopic examination showed complete blockage of the vessels by fibrin thrombi in almost all veins. The cause of this venous thrombosis was explained as a Shwartzman-Sanarelli-Phenomenon. PMID:6555120

  13. Colonic Necrosis in a 4-Year-Old with Hyperlipidemic Acute Pancreatitis

    PubMed Central

    Patton, Tiffany J.; Sentongo, Timothy A.; Mak, Grace Z.; Kahn, Stacy A.

    2016-01-01

    Here we report the case of a 4-year-old male with severe acute pancreatitis due to hyperlipidemia, who presented with abdominal pain, metabolic abnormalities, and colonic necrosis. This colonic complication was secondary to the extension of a large peripancreatic fluid collection causing direct serosal autodigestion by pancreatic enzymes. Two weeks following the initial presentation, the peripancreatic fluid collection developed into a mature pancreatic pseudocyst, which was percutaneously drained. To our knowledge, this is the youngest documented pediatric case of colonic necrosis due to severe pancreatitis and the first descriptive pediatric case of a colonic complication due to hyperlipidemia-induced acute pancreatitis. PMID:26925282

  14. Colonic Necrosis in a 4-Year-Old with Hyperlipidemic Acute Pancreatitis.

    PubMed

    Patton, Tiffany J; Sentongo, Timothy A; Mak, Grace Z; Kahn, Stacy A

    2016-01-01

    Here we report the case of a 4-year-old male with severe acute pancreatitis due to hyperlipidemia, who presented with abdominal pain, metabolic abnormalities, and colonic necrosis. This colonic complication was secondary to the extension of a large peripancreatic fluid collection causing direct serosal autodigestion by pancreatic enzymes. Two weeks following the initial presentation, the peripancreatic fluid collection developed into a mature pancreatic pseudocyst, which was percutaneously drained. To our knowledge, this is the youngest documented pediatric case of colonic necrosis due to severe pancreatitis and the first descriptive pediatric case of a colonic complication due to hyperlipidemia-induced acute pancreatitis. PMID:26925282

  15. Loss of activator of G-protein signaling 3 impairs renal tubular regeneration following acute kidney injury in rodents

    PubMed Central

    Regner, Kevin R.; Nozu, Kandai; Lanier, Stephen M.; Blumer, Joe B.; Avner, Ellis D.; Sweeney, William E.; Park, Frank

    2011-01-01

    The intracellular mechanisms underlying renal tubular epithelial cell proliferation and tubular repair following ischemia-reperfusion injury (IRI) remain poorly understood. In this report, we demonstrate that activator of G-protein signaling 3 (AGS3), an unconventional receptor-independent regulator of heterotrimeric G-protein function, influences renal tubular regeneration following IRI. In rat kidneys exposed to IRI, there was a temporal induction in renal AGS3 protein expression that peaked 72 h after reperfusion and corresponded to the repair and recovery phase following ischemic injury. Renal AGS3 expression was localized predominantly to the recovering outer medullary proximal tubular cells and was highly coexpressed with Ki-67, a marker of cell proliferation. Kidneys from mice deficient in the expression of AGS3 exhibited impaired renal tubular recovery 7 d following IRI compared to wild-type AGS3-expressing mice. Mechanistically, genetic knockdown of endogenous AGS3 mRNA and protein in renal tubular epithelial cells reduced cell proliferation in vitro. Similar reductions in renal tubular epithelial cell proliferation were observed following incubation with gallein, a selective inhibitor of Gβγ subunit activity, and lentiviral overexpression of the carboxyl-terminus of G-protein-coupled receptor kinase 2 (GRK2ct), a scavenger of Gβγ subunits. In summary, these data suggest that AGS3 acts through a novel receptor-independent mechanism to facilitate renal tubular epithelial cell proliferation and renal tubular regeneration.—Regner, K. R., Nozu, K., Lanier, S. M., Blumer, J. B., Avner, E. D., Sweeney, Jr., W. E., Park, F. Loss of activator of G-protein signaling 3 impairs renal tubular regeneration following acute kidney injury in rodents. PMID:21343176

  16. Cortical necrosis in a renal transplant

    SciTech Connect

    Blumhardt, R.; Growcock, G.; Lasher, J.C.

    1983-07-01

    The /sup 99m/Tc-DTPA renogram is a well extabished noninvasive method for evaluating and following transplanted kidneys. The examination is useful in distinguishing rejection from acute tubular necrosis as well as demonstrating several less common complications such as vascular occlusion, urinary extravasation, obstruction, and lymphocele. A previously unreported condition involving a transplant kidney (i.e., renal cortical necrosis) is described which was diagnosed with renal scintigraphy in combination with sonography.

  17. Acute Hepatic Necrosis Caused by Salmonella enterica Serotype I 4,5,12:−:1,2 in a Dog

    PubMed Central

    Meiring, Thelma; Grant, Andrew J.; Watson, Penny J.

    2015-01-01

    Acute hepatic necrosis was diagnosed in a dog. Gram staining and fluorescence in situ hybridization identified Salmonella enterica in the liver, subsequently confirmed as S. enterica serotype I 4,5,12:−:1,2. This is the first report of acute hepatic necrosis with liver failure caused by Salmonella in a dog. PMID:26292301

  18. Binge Eating Leading to Acute Gastric Dilatation, Ischemic Necrosis and Rupture -A Case Report.

    PubMed

    Dewangan, Manish; Khare, Manish Kumar; Mishra, Sumanta; Marhual, Jogesh Chandra

    2016-03-01

    Acute gastric dilatation is a rarely encountered clinical scenario in our day to day practice. This is very rapidly progressing condition and can lead to ischemic necrosis and perforation/rupture of the stomach. It could be fatal if not timely intervened. We report such a case of a 17-year-old, otherwise healthy boy, who presented with pain and distension of abdomen following binge eating episode after 24 hours of prolonged fasting. On exploration, stomach was dilated with necrosis and perforation at fundus near greater curvature. He was managed with excision of all the devitalized area and primary repair with feeding jejunostomy. The case is presented due to its rarity. Acute gastric dilatation (AGD) leading to ischemic necrosis and perforation because of binge eating episode in an otherwise healthy person is an exceptional occurrence with only few cases reported in literature. The clinician should be aware of this condition for prompt and appropriate management. PMID:27134932

  19. Binge Eating Leading to Acute Gastric Dilatation, Ischemic Necrosis and Rupture –A Case Report

    PubMed Central

    Khare, Manish Kumar; Mishra, Sumanta; Marhual, Jogesh Chandra

    2016-01-01

    Acute gastric dilatation is a rarely encountered clinical scenario in our day to day practice. This is very rapidly progressing condition and can lead to ischemic necrosis and perforation/rupture of the stomach. It could be fatal if not timely intervened. We report such a case of a 17-year-old, otherwise healthy boy, who presented with pain and distension of abdomen following binge eating episode after 24 hours of prolonged fasting. On exploration, stomach was dilated with necrosis and perforation at fundus near greater curvature. He was managed with excision of all the devitalized area and primary repair with feeding jejunostomy. The case is presented due to its rarity. Acute gastric dilatation (AGD) leading to ischemic necrosis and perforation because of binge eating episode in an otherwise healthy person is an exceptional occurrence with only few cases reported in literature. The clinician should be aware of this condition for prompt and appropriate management. PMID:27134932

  20. Acute necrosis after Gamma Knife surgery in vestibular schwannoma leading to multiple cranial nerve palsies.

    PubMed

    Kapitza, Sandra; Pangalu, Athina; Horstmann, Gerhard A; van Eck, Albert T; Regli, Luca; Tarnutzer, Alexander A

    2016-08-01

    We discuss a rare acute complication after Gamma Knife therapy (Elekta AB, Stockholm, Sweden) in a single patient. A 52-year-old woman presented with vertigo, facial weakness and hearing loss emerging 48hours following Gamma Knife radiosurgery for a right-sided vestibular schwannoma. Neurological examination 6days after symptom onset showed right-sided facial palsy, spontaneous left-beating nystagmus and pathologic head-impulse testing to the right. Pure-tone audiogram revealed right-sided sensorineural hearing loss. A diagnosis of acute vestibulocochlear and facial neuropathy was made. Brain MRI demonstrated focal contrast sparing within the schwannoma, likely related to acute radiation necrosis. Acute multiple cranial neuropathies of the cerebellopontine angle after Gamma Knife treatment should raise suspicion of acute tissue damage within the schwannoma and should result in urgent MRI. Treatment with steroids may be considered based on accompanying swelling and edema. PMID:26947104

  1. Acute infantile bilateral striatal necrosis: single-photon emission computed tomography (SPECT) imaging and review.

    PubMed

    Zevit, Noam; Steinmetz, Adam; Kornreich, Liora; Straussberg, Rachel

    2007-10-01

    Acute infantile bilateral striatal necrosis is a rarely described acute neurological syndrome associated with radiological findings. Its etiology and pathogenic mechanisms are unknown. Clinically, the syndrome usually follows respiratory illnesses and presents with an array of neurological findings, including axial ataxia, grimacing, mutism, head nodding, and high-pitched cry. This study follows a child with acute infantile bilateral striatal necrosis both clinically and radiologically. In addition, for the first time, the authors describe the serial findings of single-photon emission computed tomography (SPECT) from onset of illness through 20 months. Their findings indicate an initial insult apparent on both magnetic resonance imaging and SPECT localized to the basal ganglia, which, although improved over time, does not fully regress. The residual lesion on SPECT was clinically associated with only mild attention deficit disorder and no motor pathology. The authors review the published literature concerning acute infantile bilateral striatal necrosis and suggest possible mechanisms of this poorly understood and probably underreported condition. PMID:17940250

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

    PubMed Central

    Wang, Jun; Al-Lamki, Rafia S.

    2013-01-01

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

  3. Good visual outcome in an immunocompromised patient with bilateral acute retinal necrosis syndrome: A case report

    PubMed Central

    Marrocos de Aragão, Ricardo E.; Barreira, Ieda M.A.; Arrais, Barbara L.A.; Pereira, Leidiane A.; Ramos, Carine S.

    2013-01-01

    Acute retinal necrosis (ARN) is an uncommon necrotizing, fulminant retinopathy caused by the herpes simplex virus types 1 or 2 or by the varicella zoster vírus with visually devastating consequences. Generally it occurs in patients who are systemically healthy, but occasionally occurs in immunocompromised host. We report a case of bilateral ARN in a patient with AIDS with a good final visual outcome. PMID:25278806

  4. Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura

    PubMed Central

    Bernstein, Gregory R.; Malik, Zubair; Schey, Ron

    2015-01-01

    A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis. PMID:26504868

  5. Metformin Protects Against Cisplatin-Induced Tubular Cell Apoptosis and Acute Kidney Injury via AMPKα-regulated Autophagy Induction

    PubMed Central

    Li, Jianzhong; Gui, Yuan; Ren, Jiafa; Liu, Xin; Feng, Ye; Zeng, Zhifeng; He, Weichun; Yang, Junwei; Dai, Chunsun

    2016-01-01

    Metformin, one of the most common prescriptions for patients with type 2 diabetes, is reported to protect the kidney from gentamicin-induced nephrotoxicity. However, the role and mechanisms for metformin in preventing cisplatin-induced nephrotoxicity remains largely unknown. In this study, a single intraperitoneal injection of cisplatin was employed to induce acute kidney injury (AKI) in CD1 mice. The mice exhibited severe kidney dysfunction and histological damage at day 2 after cisplatin injection. Pretreatment of metformin could markedly attenuate cisplatin-induced acute kidney injury, tubular cell apoptosis and inflammatory cell accumulation in the kidneys. Additionally, pretreatment of metformin could enhance both AMPKα phosphorylation and autophagy induction in the kidneys after cisplatin injection. In cultured NRK-52E cells, a rat kidney tubular cell line, metformin could stimulate AMPKα phosphorylation, induce autophagy and inhibit cisplatin-induced cell apoptosis. Blockade of either AMPKα activation or autophagy induction could largely abolish the protective effect of metformin in cisplatin-induced cell death. Together, this study demonstrated that metformin may protect against cisplatin-induced tubular cell apoptosis and AKI through stimulating AMPKα activation and autophagy induction in the tubular cells. PMID:27052588

  6. 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

  7. 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. PMID:26136687

  8. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression

    PubMed Central

    Leventhal, Jeremy S.; Ni, Jie; Osmond, Morgan; Lee, Kyung; Gusella, G. Luca; Salem, Fadi; Ross, Michael J.

    2016-01-01

    Sepsis related acute kidney injury (AKI) is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC) from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS), a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO). Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3) and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling. PMID:26990086

  9. 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

  10. Effects of reserpine and L-cysteine and glutathione depletion on 2-bromoethylamine hydrobromide-induced tubular necrosis in Swiss ICR mice.

    PubMed

    Wolf, D C; Carlson, G P; DeNicola, D B; Carlton, W W

    1991-08-01

    Female Swiss ICR mice were injected ip with 100 or 300 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight. Male Swiss ICR mice were subjected to water deprivation, or treated with 5% dextrose in water, dimethylsulphoxide, piperonyl butoxide, SKF-525A, sodium phenobarbital, beta-naphthoflavone, probenecid, reserpine, diethyl maleate, buthionine sulphoximine or L-cysteine. Urine collected sequentially from male Swiss ICR mice given 300 mg BEA/kg body weight was analysed for glucose, protein, pH and specific gravity. Female mice were less sensitive to BEA than were male mice. Diuresis, antidiuresis, treatment with cytochrome P-450 inducers and inhibitors, and the antioxidant dimethyl-sulphoxide had no effect on the incidence or severity of tubular necrosis (TN) induced by BEA. Probenecid and L-cysteine decreased the severity, but they had no effect on the incidence of TN. Glutathione depletion by diethyl maleate and inhibition of glutathione synthesis by buthionine sulphoximine decreased the dose of BEA necessary to cause TN; buthionine sulphoximine was more effective than diethyl maleate. Reserpine decreased both the incidence and severity of TN. Glycosuria, aciduria and decreased urinary specific gravity occurred before morphological changes were seen under the microscope, indicating that the functional changes precede the morphological changes. These data indicate that glutathione is important in protecting against BEA-induced TN, that BEA or a metabolite is concentrated in the tubule epithelium by way of anion transport, and that vasoconstriction contributes to the development of BEA-induced TN. PMID:1894223

  11. Duration of injury correlates with necrosis in caerulein-induced experimental acute pancreatitis: implications for pathophysiology

    PubMed Central

    Jacob, Tony G; Raghav, Rahul; Kumar, Ajay; Garg, Pramod K; Roy, Tara S

    2014-01-01

    Pancreatic acinar cell necrosis is indicative of severe pancreatitis and the degree of necrosis is an index of its outcome. We studied whether the dose and duration of injury correlates with severity, particularly in terms of necrosis, in caerulein-induced acute pancreatitis (AP) in Swiss albino mice. In addition to control group 1 (G1), groups 2 and 3 received four injections of caerulein every hour but were sacrificed at five hours (G2) and nine hours (G3) respectively, and group 4 received eight injections and was sacrificed at nine hours (G4). The severity of pancreatitis was assessed histopathologically and biochemically. The histopathological scores of pancreatitis in groups 3 and 4 were significantly higher than in groups 1 and 2 (4 vs. 1, 4 vs. 2, 3 vs. 1, 3 vs. 2; P < 0.05). TUNEL-positive apoptotic cells were significantly higher in groups 2 and 3 compared with groups 1 and 4 (P < 0.05). Necrosis was significantly more in group 4 than other groups (37.49% (4.68) vs. 19.97% (1.60) in G2; 20.36% (1.56) in G3; P = 0.006 for G 2 vs. 4 and P = 0.019 for G 3 vs. 4). Electron microscopy revealed numerous autophagosomes in groups 2 and 3 and mitochondrial damage and necrosis in group 4. The pancreatic and pulmonary myeloperoxidase activity in group 4 was significantly higher than that in the other groups (P < 0.01). Hence, severity of pancreatitis is a function of the dose of injurious agent, while inflammation is both dose and duration dependent, which may also explain the wide spectrum of severity of AP seen in clinical practice. PMID:24761825

  12. Glomerular and tubular adaptive responses to acute nephron loss in the rat. Effect of prostaglandin synthesis inhibition.

    PubMed Central

    Pelayo, J C; Shanley, P F

    1990-01-01

    These studies, using in vivo micropuncture techniques in the Munich-Wistar rat, document the magnitude of changes in glomerular and tubular function and structure 24 h after approximately 75% nephron loss (Nx) and compared these results with those obtained in sham-operated rats. The contribution of either nephron hypertrophy or renal prostaglandin to these adjustments in nephron function was also explored. After acute Nx, single nephron GFR (SNGFR) was increased, on average by approximately 30%, due primarily to glomerular hyperperfusion and hypertension. The approximately 45% reduction in preglomerular and the constancy in postglomerular vascular resistances was entirely responsible for these adaptations. Although increases in fluid reabsorption in proximal convoluted tubules correlated closely with increase in SNGFR, the fractional fluid reabsorption between late proximal and early distal tubular segments was depressed. Nephron hypertrophy could not be substantiated based on either measurements of protein content in renal tissue homogenates or morphometric analysis of proximal convoluted tubules. However, acute Nx was associated with increased urinary excretory rates per functional nephron for 6-keto-PGF1 alpha and TXB2. Prostaglandin synthesis inhibition did not affect function in control nephrons, but this maneuver was associated with normalization of glomerular and tubular function in remnant nephrons. The results suggest that enhanced synthesis of cyclooxygenase-dependent products is one of the earliest responses to Nx, and even before hypertrophy the pathophysiologic effects of prostaglandin may be important contributors to the adaptations in remnant nephron function. PMID:1693376

  13. A case of presumed acute retinal necrosis after intraocular foreign body injury.

    PubMed

    Park, Sung Who; Byon, Ik Soo; Park, Hyun Jun; Lee, Ji Eun; Oum, Boo Sup

    2013-01-01

    The aim of this study was to report a case of acute retinal necrosis (ARN) after intraocular foreign body removal. A 32-year-old male presented with visual loss in the left eye. He was hit by an iron fragment while he was hammering. An intraocular foreign body was found with corneal laceration and traumatic cataract. On the day he was injured, primary closure of the laceration, lensectomy, and vitrectomy were performed, and the foreign body was removed. The day after the operation, there was no sign of retinal detachment or retinitis. Two days after the operation, retinal necrosis and accompanying vitreous inflammation were noted in the far periphery. On day 3, the necrosis spread circumferentially and inflammation became more distinct. ARN was presumed and intravenous acyclovir was administered. The necrotic areas were reduced 2 days later, and were resolved in 1 month. The final visual acuity in his left eye was 20/20 after implantation of an intraocular lens. This case is the first report of ARN after penetrating injury and an intraocular foreign body. ARN may develop after open-globe injury. PMID:23658473

  14. Mitochondria Play a Central Role in Nonischemic Cardiomyocyte Necrosis: Common to Acute and Chronic Stressor States

    PubMed Central

    Khan, M. Usman; Cheema, Yaser; Shahbaz, Atta U.; Ahokas, Robert A.; Sun, Yao; Gerling, Ivan C.; Bhattacharya, Syamal K.; Weber, Karl T.

    2012-01-01

    The survival of cardiomyocytes must be ensured as the myocardium adjusts to a myriad of competing physiologic and pathophysiologic demands. A significant loss of these contractile cells, together with their replacement by stiff fibrillar collagen in the form of fibrous tissue accounts for a transition from a usually efficient muscular pump into one that is failing. Cellular and subcellular mechanisms involved in the pathogenic origins of cardiomyocyte cell death have long been of interest. This includes programmed molecular pathways to either necrosis or apoptosis which are initiated from ischemic or nonischemic origins. Herein we focus on the central role played by a mitochondriocentric signal-transducer-effector pathway to nonischemic cardiomyocyte necrosis which is common to acute and chronic stressor states. We begin by building upon the hypothesis advanced by Albrecht Fleckenstein and coworkers some 40 years ago based on the importance of calcitropic hormone- mediated intracellular Ca2+ overloading which predominantly involves subsarcolemmal mitochondria and is the signal to pathway activation. Other pathway components, which came to be recognized in subsequent years, include the induction of oxidative stress and opening of the mitochondrial inner membrane permeability transition pore. The ensuing loss of cardiomyocytes and consequent replacement fibrosis, or scarring, represents a disease of adaptation and a classic example of when homeostasis begets dyshomeostasis. PMID:22328074

  15. Mitochondria play a central role in nonischemic cardiomyocyte necrosis: common to acute and chronic stressor states.

    PubMed

    Khan, M Usman; Cheema, Yaser; Shahbaz, Atta U; Ahokas, Robert A; Sun, Yao; Gerling, Ivan C; Bhattacharya, Syamal K; Weber, Karl T

    2012-07-01

    The survival of cardiomyocytes must be ensured as the myocardium adjusts to a myriad of competing physiological and pathophysiological demands. A significant loss of these contractile cells, together with their replacement by stiff fibrillar collagen in the form of fibrous tissue accounts for a transition from a usually efficient muscular pump into one that is failing. Cellular and subcellular mechanisms involved in the pathogenic origins of cardiomyocyte cell death have long been of interest. This includes programmed molecular pathways to either necrosis or apoptosis, which are initiated from ischemic or nonischemic origins. Herein, we focus on the central role played by a mitochondriocentric signal-transducer-effector pathway to nonischemic cardiomyocyte necrosis, which is common to acute and chronic stressor states. We begin by building upon the hypothesis advanced by Albrecht Fleckenstein and coworkers some 40 years ago based on the importance of calcitropic hormone-mediated intracellular Ca(2+) overloading, which predominantly involves subsarcolemmal mitochondria and is the signal to pathway activation. Other pathway components, which came to be recognized in subsequent years, include the induction of oxidative stress and opening of the mitochondrial inner membrane permeability transition pore. The ensuing loss of cardiomyocytes and consequent replacement fibrosis, or scarring, represents a disease of adaptation and a classic example of when homeostasis begets dyshomeostasis. PMID:22328074

  16. Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis.

    PubMed

    Fong, Choong Yi; Aye, Aye Mya Min; Peyman, Mohammadreza; Nor, Norazlin Kamal; Visvaraja, Subrayan; Tajunisah, Iqbal; Ong, Lai Choo

    2014-04-01

    We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease. PMID:24378951

  17. Effects of cytokines on potassium channels in renal tubular epithelia.

    PubMed

    Nakamura, Kazuyoshi; Komagiri, You; Kubokawa, Manabu

    2012-02-01

    Renal tubular potassium (K(+)) channels play important roles in the formation of cell-negative potential, K(+) recycling, K(+) secretion, and cell volume regulation. In addition to these physiological roles, it was reported that changes in the activity of renal tubular K(+) channels were involved in exacerbation of renal cell injury during ischemia and endotoxemia. Because ischemia and endotoxemia stimulate production of cytokines in immune cells and renal tubular cells, it is possible that cytokines would affect K(+) channel activity. Although the regulatory mechanisms of renal tubular K(+) channels have extensively been studied, little information is available about the effects of cytokines on these K(+) channels. The first report was that tumor necrosis factor acutely stimulated the single channel activity of the 70 pS K(+) channel in the rat thick ascending limb through activation of tyrosine phosphatase. Recently, it was also reported that interferon-γ (IFN-γ) and interleukin-1β (IL-1β) modulated the activity of the 40 pS K(+) channel in cultured human proximal tubule cells. IFN-γ exhibited a delayed suppression and an acute stimulation of K(+) channel activity, whereas IL-1β acutely suppressed the channel activity. Furthermore, these cytokines suppressed gene expression of the renal outer medullary potassium channel. The renal tubular K(+) channels are functionally coupled to the coexisting transporters. Therefore, the effects of cytokines on renal tubular transporter activity should also be taken into account, when interpreting their effects on K(+) channel activity. PMID:22042037

  18. Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis

    PubMed Central

    Oliveira, Marina C.; Tavares, Luciana P.; Vago, Juliana P.; Batista, Nathália V.; Queiroz-Junior, Celso M.; Vieira, Angelica T.; Menezes, Gustavo B.; Sousa, Lirlândia P.; van de Loo, Fons A. J.; Teixeira, Mauro M.; Amaral, Flávio A.; Ferreira, Adaliene V. M.

    2016-01-01

    Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines. PMID:26742100

  19. Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis.

    PubMed

    Oliveira, Marina C; Tavares, Luciana P; Vago, Juliana P; Batista, Nathália V; Queiroz-Junior, Celso M; Vieira, Angelica T; Menezes, Gustavo B; Sousa, Lirlândia P; van de Loo, Fons A J; Teixeira, Mauro M; Amaral, Flávio A; Ferreira, Adaliene V M

    2016-01-01

    Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines. PMID:26742100

  20. The cardiac surgery-associated neutrophil gelatinase-associated lipocalin (CSA-NGAL) score: A potential tool to monitor acute tubular damage.

    PubMed

    de Geus, Hilde R H; Ronco, Claudio; Haase, Michael; Jacob, Laurent; Lewington, Andrew; Vincent, Jean-Louis

    2016-06-01

    Acute kidney injury (AKI), defined as a rise in serum creatinine (functional AKI), is a frequent complication after cardiac surgery. The expression pattern of acute tubular damage biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) has been shown to precede functional AKI and, therefore, may be useful to identify very early tubular damage. The term subclinical AKI represents acute tubular damage in the absence of functional AKI (biomarker positivity without a rise in serum creatinine) and affects hard outcome measures. This potentiates an tubular-damage-based identification of renal injury, which may guide clinical management, allowing for very early preventive-protective strategies. The aim of this paper was to review the current available evidence on NGAL applicability in adult cardiac surgery patients and combine this knowledge with the expert consensus of the authors to generate an NGAL based tubular damage score: The cardiac surgery-associated NGAL Score (CSA-NGAL score). The CSA-NGAL score might be the tool needed to improve awareness and enable interventions to possibly modify these detrimental outcomes. In boldly doing so, it is intended to introduce a different approach in study designs, which will undoubtedly expand our knowledge and will hopefully move the AKI biomarker field forward. PMID:26952930

  1. Histamine receptor antagonists, cyclooxygenase blockade, and tumor necrosis factor during acute septic insult.

    PubMed

    Leeper-Woodford, S K; Carey, D; Byrne, K; Walsh, C; Fisher, B; Sugerman, H J; Fowler, A A

    1998-02-01

    Tumor necrosis factor (TNF) may be a major endogenous mediator of sepsis-induced acute organ injury. We proposed that treatment of septic pigs with the combined agents ibuprofen, a cyclooxygenase inhibitor, and histamine receptor antagonists, cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) would result in lower circulating levels of TNF and decreased parameters of sepsis-induced injury in these animals. To test this, plasma TNF activity, cardiac index, systemic and pulmonary arterial pressures, arterial PO2 and bronchoalveolar lavage protein content were monitored for 300 min in four groups of anesthetized pigs: saline-infused control pigs (n = 4); pigs infused for 60 min with Pseudomonas aeruginosa (5 x 10(8) organisms/mL, .3 mL/20 kg/min) (n = 5) and pigs infused for 60 min with P. aeruginosa plus ibuprofen (12.5 mg/kg) alone (n = 4) or ibuprofen plus cimetidine (150 mg) and diphenhydramine (30 mg/kg) at 0 and 120 min (CID, n = 4). Within 60 min, pigs infused with P. aeruginosa exhibited increased plasma TNF activity (>8-fold increase in ng/mL TNF; L929 cytolysis assay) and showed alterations in all hemodynamic and pulmonary parameters. Ibuprofen or CID administration in the septic pigs decreased peak TNF activity by 4.6 and 10.2 ng/mL, respectively, and CID treatment was correlated with better attenuation of certain sepsis-induced alterations. These results show that CID treatment attenuates sepsis-induced injury and that this is correlated with reduced plasma TNF activity in a porcine model of sepsis-induced acute organ injury. PMID:9488252

  2. Characterization of Vibrio parahaemolyticus causing acute hepatopancreatic necrosis disease in southern Thailand.

    PubMed

    Kongrueng, J; Yingkajorn, M; Bunpa, S; Sermwittayawong, N; Singkhamanan, K; Vuddhakul, V

    2015-11-01

    Vibrio parahaemolyticus was isolated from shrimp of five farms located in the Pattani and Songkhla provinces of southern Thailand. Using a PCR method targeted to the unique DNA sequences derived from the plasmid (AP2 primers) and the toxin gene (AP3 primers) of V. parahaemolyticus that caused acute hepatopancreatic necrosis disease (AHPND), a total of 33 of 108 isolates were positive. In contrast, all 63 and 66 isolates of clinical and environmental V. parahaemolyticus, respectively, obtained previously from 2008 to 2014 from the same area were negative. This implied that these strains were likely to be the cause of the outbreak of AHPND in this area. Intestinal samples proved to be a better source for the isolation of V. parahaemolyticus AHPND than the hepatopancreas. All isolates were investigated for haemolytic activity, virulence genes, serotypes, genotypes and antibiotic susceptibility. All the AHPND isolates had a unique O antigen, but small variations of the K antigens were detected from different farms. In addition, the DNA profiles of V. parahaemolyticus AHPND isolates were similar, but distinct from those clinical and environmental isolates. It is postulated that the causative agent of AHPND might have originated from one clone and then slightly different serotypes subsequently developed. PMID:25287127

  3. Spontaneous Proliferation of H2M-/- CD4 T Cells Results in Unusual Acute Hepatocellular Necrosis

    PubMed Central

    Do, Jeong-su; Baldwin, William M.; Min, Booki

    2014-01-01

    Naïve CD4 T cells are triggered to undergo spontaneous proliferation, a proliferative response induced in response to homeostatic stimulation, when exposed to severe lymphopenic environments. They spontaneously acquire proinflammatory effector phenotypes, playing a major role in inducing chronic inflammation in the intestine that is believed to be induced by T cell recognition of commensal antigens. While the antigens inducing the T cell responses and inflammation are being extensively investigated, the role of clonality of T cells involved in this process remains poorly understood. In this study, we utilized naïve CD4 T cells isolated from B6 H2M−/− mice, in which MHCII molecules are complexed with a single CLIP molecule, and examined spontaneous proliferation and intestinal inflammation of CD4 T cells expressing limited T cell receptor repertoire diversity. We found that H2M−/− CD4 T cells undergo robust spontaneous proliferation, differentiate into IFNγ-producing Th1 type effector cells, and, most unexpectedly, induce severe acute hepatocellular necrosis. T cell interaction with MHCII molecule on cells of hematopoietic origin was essential to induce the pathology. Interestingly, B cells are fully capable of preventing necrotic inflammation via IL-10-independent and B7-H1-dependent mechanism. This could be a useful animal model to examine T cell-mediated liver inflammation and B cell-mediated immune regulation. PMID:25313460

  4. Acute Retinal Necrosis Associated with Epstein-Barr Virus in a Patient Undergoing Immunosuppressive Therapy

    PubMed Central

    Oe, Chiaki; Hiraoka, Miki; Tanaka, Sachie; Ohguro, Hiroshi

    2016-01-01

    Acute retinal necrosis (ARN) is a rapidly progressive and severe retinitis resulting in a poor visual outcome. Infections caused by herpes viruses such as herpes simplex virus (HSV) types 1 and 2 or the varicella zoster virus (VZV) are known to be implicated in the development of ARN. In the present study, an 80-year-old female with ARN was examined. She had been affected with rheumatoid arthritis and had taken methotrexate for over 10 years. Her right eye showed clinical features of ARN, and her left eye showed mild retinitis. The genomic DNA in the aqueous humor and vitreous fluid from her right eye were analyzed by a comprehensive polymerase chain reaction (PCR) assay to screen infectious pathogens including viruses. The Epstein-Barr virus (EBV) was detected from both specimens, but neither HSV or VZV nor cytomegalovirus was detected. She underwent intraocular surgery following systemic corticosteroid and acyclovir applications. However, although the retinitis of her right eye was extinguished, the final visual outcome was blindness due to optic nerve atrophy. There are few reports indicating that EBV is associated with ARN development. The present findings suggest that EBV alone can be the causative agent of ARN. PMID:27194989

  5. Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study

    PubMed Central

    Cochrane, T F; Silvestri, G; McDowell, C; Foot, B; McAvoy, C E

    2012-01-01

    Background To determine the incidence of acute retinal necrosis (ARN) in the United Kingdom and to describe the demographics, management, and visual outcome in these patients. Methods This was a prospective study carried out by the British Ophthalmological Surveillance Unit (BOSU) between September 2007 and October 2008. Initial and 6-month questionnaires were sent to UK ophthalmologists who reported cases of ARN via the monthly BOSU report card system. Results In all, 45 confirmed cases (52 eyes) of ARN were reported in the 14-month study period, giving a minimum incidence of 0.63 cases per million population per year. There were 20 females and 25 males. Age ranged from 10 to 94 years. Eight patients had a history of herpetic CNS disease. Aqueous sampling was carried out in 13 patients, vitreous in 27, and cerebrospinal fluid (CSF) in 4. Varicella-zoster virus followed by herpes simplex were the most common causative agents. Treatment in 76% of the cases was with intravenous antivirals; however, 24% received only oral antivirals. In all, 47% of patients had intravitreal antiviral therapy. Visual outcome at 6 months was <6/60 in 48% of the affected eyes. Conclusion The minimum incidence of ARN in the UK is 0.63 cases per million. Patients with a history of herpetic CNS disease should be warned to immediately report any visual symptoms. There is increased use of oral and intravitreal antivirals in initial treatment. PMID:22281865

  6. Late Metabolic Acidosis Caused by Renal Tubular Acidosis in Acute Salicylate Poisoning.

    PubMed

    Sakai, Norihiro; Hirose, Yasuo; Sato, Nobuhiro; Kondo, Daisuke; Shimada, Yuko; Hori, Yasushi

    2016-01-01

    A 16-year-old man was transferred to our emergency department seven hours after ingesting 486 aspirin tablets. His blood salicylate level was 83.7 mg/dL. He was treated with fluid resuscitation and sodium bicarbonate infusion, and his condition gradually improved, with a decline in the blood salicylate level. However, eight days after admission, he again reported nausea, a venous blood gas revealed metabolic acidosis with a normal anion gap. The blood salicylate level was undetectable, and a urinalysis showed glycosuria, proteinuria and elevated beta-2 microglobulin and n-acetyl glucosamine levels, with a normal urinary pH despite the acidosis. We diagnosed him with relapse of metabolic acidosis caused by renal tubular acidosis. PMID:27181539

  7. Field and Experimental Evidence of Vibrio parahaemolyticus as the Causative Agent of Acute Hepatopancreatic Necrosis Disease of Cultured Shrimp (Litopenaeus vannamei) in Northwestern Mexico

    PubMed Central

    Gomez-Gil, Bruno; Lozano-Olvera, Rodolfo; Betancourt-Lozano, Miguel; Morales-Covarrubias, Maria Soledad

    2014-01-01

    Moribund shrimp affected by acute hepatopancreatic necrosis disease (AHPND) from farms in northwestern Mexico were sampled for bacteriological and histological analysis. Bacterial isolates were molecularly identified as Vibrio parahaemolyticus by the presence of the tlh gene. The tdh-negative, trh-negative, and tlh-positive V. parahaemolyticus strains were further characterized by repetitive extragenic palindromic element-PCR (rep-PCR), and primers AP1, AP2, AP3, and AP and an ems2 IQ2000 detection kit (GeneReach, Taiwan) were used in the diagnostic tests for AHPND. The V. parahaemolyticus strains were used in immersion challenges with shrimp, and farmed and challenged shrimp presented the same clinical and pathological symptoms: lethargy, empty gut, pale and aqueous hepatopancreas, and expanded chromatophores. Using histological analysis and bacterial density count, three stages of AHNPD (initial, acute, and terminal) were identified in the affected shrimp. The pathognomonic lesions indicating severe desquamation of tubular epithelial cells of the hepatopancreas were observed in both challenged and pond-infected shrimp. The results showed that different V. parahaemolyticus strains have different virulences; some of the less virulent strains do not induce 100% mortality, and mortality rates also rise more slowly than they do for the more virulent strains. The virulence of V. parahaemolyticus strains was dose dependent, where the threshold infective density was 104 CFU ml−1; below that density, no mortality was observed. The AP3 primer set had the best sensitivity and specificity. Field and experimental results showed that the V. parahaemolyticus strain that causes AHPND acts as a primary pathogen for shrimp in Mexico compared with the V. parahaemolyticus strains reported to date. PMID:25548045

  8. Field and experimental evidence of Vibrio parahaemolyticus as the causative agent of acute hepatopancreatic necrosis disease of cultured shrimp (Litopenaeus vannamei) in Northwestern Mexico.

    PubMed

    Soto-Rodriguez, Sonia A; Gomez-Gil, Bruno; Lozano-Olvera, Rodolfo; Betancourt-Lozano, Miguel; Morales-Covarrubias, Maria Soledad

    2015-03-01

    Moribund shrimp affected by acute hepatopancreatic necrosis disease (AHPND) from farms in northwestern Mexico were sampled for bacteriological and histological analysis. Bacterial isolates were molecularly identified as Vibrio parahaemolyticus by the presence of the tlh gene. The tdh-negative, trh-negative, and tlh-positive V. parahaemolyticus strains were further characterized by repetitive extragenic palindromic element-PCR (rep-PCR), and primers AP1, AP2, AP3, and AP and an ems2 IQ2000 detection kit (GeneReach, Taiwan) were used in the diagnostic tests for AHPND. The V. parahaemolyticus strains were used in immersion challenges with shrimp, and farmed and challenged shrimp presented the same clinical and pathological symptoms: lethargy, empty gut, pale and aqueous hepatopancreas, and expanded chromatophores. Using histological analysis and bacterial density count, three stages of AHNPD (initial, acute, and terminal) were identified in the affected shrimp. The pathognomonic lesions indicating severe desquamation of tubular epithelial cells of the hepatopancreas were observed in both challenged and pond-infected shrimp. The results showed that different V. parahaemolyticus strains have different virulences; some of the less virulent strains do not induce 100% mortality, and mortality rates also rise more slowly than they do for the more virulent strains. The virulence of V. parahaemolyticus strains was dose dependent, where the threshold infective density was 10(4) CFU ml(-1); below that density, no mortality was observed. The AP3 primer set had the best sensitivity and specificity. Field and experimental results showed that the V. parahaemolyticus strain that causes AHPND acts as a primary pathogen for shrimp in Mexico compared with the V. parahaemolyticus strains reported to date. PMID:25548045

  9. Gastrointestinal Fistulas in Acute Pancreatitis With Infected Pancreatic or Peripancreatic Necrosis

    PubMed Central

    Jiang, Wei; Tong, Zhihui; Yang, Dongliang; Ke, Lu; Shen, Xiao; Zhou, Jing; Li, Gang; Li, Weiqin; Li, Jieshou

    2016-01-01

    Abstract Gastrointestinal (GI) fistula is a well-recognized complication of acute pancreatitis (AP). However, it has been reported in limited literature. This study aimed to evaluate the incidence and outcome of GI fistulas in AP patients complicated with infected pancreatic or peripancreatic necrosis (IPN). Between 2010 and 2013 AP patients with IPN who diagnosed with GI fistula in our center were analyzed in this retrospective study. And we also conducted a comparison between patients with and without GI fistula regarding the baseline characteristics and outcomes. Over 4 years, a total of 928 AP patients were admitted into our center, of whom 119 patients with IPN were diagnosed with GI fistula and they developed 160 GI fistulas in total. Colonic fistula found in 72 patients was the most common form of GI fistula followed with duodenal fistula. All duodenal fistulas were managed by nonsurgical management. Ileostomy or colostomy was performed for 44 (61.1%) of 72 colonic fistulas. Twenty-one (29.2%) colonic fistulas were successfully treated by percutaneous drainage or continuous negative pressure irrigation. Mortality of patients with GI fistula did not differ significantly from those without GI fistula (28.6% vs 21.9%, P = 0.22). However, a significantly higher mortality (34.7%) was observed in those with colonic fistula. GI fistula is a common finding in patients of AP with IPN. Most of these fistulas can be successfully managed with different procedures depending on their sites of origin. Colonic fistula is related with higher mortality than those without GI fistula. PMID:27057908

  10. Myocardial uptake of indium-111-labeled antimyosin in acute subendocardial infarction: Clinical, histochemical, and autoradiographic correlation of myocardial necrosis

    SciTech Connect

    Hendel, R.C.; McSherry, B.A.; Leppo, J.A. )

    1990-11-01

    Indium-111-labeled antimyosin has been utilized in the diagnosis and localization of acute transmural myocardial infarction. The present report describes a patient who presented with a massive subendocardial infarction. Two days after the injection of antimyosin, the patient's clinical status markedly deteriorated and he expired. Postmortem examination demonstrated severe three-vessel coronary artery disease with extensive myocyte death in the endocardium. Autoradiography and histochemical staining of the prosected heart demonstrated high correlation for myocardial necrosis and corresponded to clinical evidence for diffuse subendocardial infarction.

  11. Calcitriol inhibits tumor necrosis factor alpha and macrophage inflammatory protein-2 during lipopolysaccharide-induced acute lung injury in mice.

    PubMed

    Tan, Zhu-Xia; Chen, Yuan-Hua; Xu, Shen; Qin, Hou-Ying; Wang, Hua; Zhang, Cheng; Xu, De-Xiang; Zhao, Hui

    2016-08-01

    Acute lung injury is a common complication of sepsis in intensive care unit patients with an extremely high mortality. The present study investigated the effects of calcitriol, the active form of vitamin D, on tumor necrosis factor alpha (TNF-α) and macrophage inflammatory protein-2 (MIP-2) in sepsis-induced acute lung injury. Mice were intraperitoneally (i.p.) injected with lipopolysaccharide (LPS, 1.0mg/kg) to establish the animal model of sepsis-induced acute lung injury. Some mice were i.p. injected with calcitriol (1.0μg/kg) before LPS injection. An obvious infiltration of inflammatory cells in the lungs was observed beginning at 1h after LPS injection. Correspondingly, TNF-α and MIP-2 in sera and lung homogenates were markedly elevated in LPS-treated mice. Interestingly, calcitriol obviously alleviated LPS-induced infiltration of inflammatory cells in the lungs. Moreover, calcitriol markedly attenuated LPS-induced elevation of TNF-α and MIP-2 in sera and lung homogenates. Further analysis showed that calcitriol repressed LPS-induced p38 mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) phosphorylation. In addition, calcitriol blocked LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 and p50 subunit in the lungs. Taken together, these results suggest that calcitriol inhibits inflammatory cytokines production in LPS-induced acute lung injury. PMID:27216047

  12. Successful Endoscopic Management of Acute Necrotic Pancreatitis and Walled Off Necrosis After Auxiliary Partial Orthotopic Living-Donor Liver Transplantation: A Case Report.

    PubMed

    Kobayashi, T; Miura, K; Ishikawa, H; Soma, D; Zhang, Z; Yuza, K; Hirose, Y; Takizawa, K; Nagahashi, M; Sakata, J; Kameyama, H; Kosugi, S; Wakai, T

    2016-05-01

    Endoscopic management of acute necrotic pancreatitis and walled off necrosis is less invasive than surgical treatment and has become the 1st choice for treating pancreatic necrosis and abscess. We treated a case of acute necrotic pancreatitis and walled off necrosis after auxiliary partial orthotopic living-donor liver transplantation (APOLT). A 24-year-old woman was admitted to our university hospital for removal of the internal biliary stent, which had already been placed endoscopically for the treatment of biliary stricture after APOLT. She had been treated for acute liver failure by APOLT 10 years before. After we removed the internal stent with the use of an endoscopic retrograde approach, she presented with severe abdominal pain and a high fever. Her diagnosis was severe acute pancreatitis after endoscopic retrograde cholangiography (ERC). Her symptoms worsened, and she had multiple organ failure. She was transferred to the intensive care unit (ICU). Immunosuppression was discontinued because infection treatment was necessary and the native liver had already recovered sufficiently. After she had been treated for 19 days in the ICU, she recovered from her multiple organ failure. However, abdominal computerized tomography demonstrated the formation of pancreatic walled off necrosis and an abscess on the 20th day after ERC. We performed endoscopic ultrasonography-guided abscess drainage and repeated endoscopic necrosectomy. The walled off necrosis diminished gradually in size, and the symptoms disappeared. The patient was discharged on the 87th day after ERC. This is the 1st report of a case of acute necrotic pancreatitis and walled off necrosis that was successfully treated by endoscopic management after APOLT. PMID:27320589

  13. Rapamycin Treatment of Healthy Pigs Subjected to Acute Myocardial Ischemia-Reperfusion Injury Attenuates Cardiac Functions and Increases Myocardial Necrosis

    PubMed Central

    Lassaletta, Antonio D; Elmadhun, Nassrene Y; Zanetti, Arthus V D; Feng, Jun; Anduaga, Javier; Gohh, Reginald Y.; Sellke, Frank W; Bianchi, Cesario

    2013-01-01

    Background The Mechanistic Target of Rapamycin (mTOR) pathway is a major regulator of cell immunity and metabolism. mTOR is a well-known suppressor of tissue rejection in organ transplants, however, it has other non-immune functions including in the cardiovascular system, where it is a regulator of heart hypertrophy and locally, in coated vascular stents, inhibits vascular wall cell growth and hence neointimal formation/restenosis. Because the mTOR pathway plays major roles in normal cell growth, metabolism and survival, we hypothesized that inhibiting it with rapamycin, prior to an acute myocardial ischemia-reperfusion injury (IRI), would confer cardioprotection by virtue of slowing down cardiac function and metabolism. Methods Yorkshire pigs received orally either placebo or 4 mg/day rapamycin for 7 days before the IRI. All animals underwent median sternotomy and the mid-left anterior descending coronary artery was occluded for 60 min followed by 120 min of reperfusion. Left ventricular pressure-volume data was collected throughout the operation. The ischemic and infarcted areas were determined by monastral blue and triphenyltetrazolium chloride staining, respectively and plasma cardiac troponin I concentration. mTOR kinase activities were monitored in remote cardiac tissue by western blotting with specific antibodies against specific substrates phosphorylating sites. Results Rapamycin pre-treatement impaired endothelial-dependent vasorelaxation, attenuated cardiac function during IRI, and increased myocardial necrosis. Western blotting confirmed effective inhibition of myocardial mTOR kinase activities. Conclusions Pre-treatment of healthy pigs with rapamycin prior to acute myocardial IRI is associated with decreased cardiac function and higher myocardial necrosis. PMID:24266948

  14. Assessment of acute myocardial necrosis after cardiopulmonary resuscitation and cardioversion by means of combined thallium-201/technetium-99m pyrophosphate tomography.

    PubMed

    Krause, T; Hohnloser, S H; Kasper, W; Schümichen, C; Reinhardt, M; Moser, E

    1995-11-01

    Diagnosis of acute myocardial necrosis by means of conventional electrocardiographic criteria or the release of cardiac enzymes is often difficult or even impossible in patients with out-of-hospital cardiac arrest due to ventricular fibrillation with subsequent cardiopulmonary resuscitation including several DC countershocks. Simultaneous thallium-201/technetium-99m pyrophosphate (PYP) tomography was prospectively applied to 57 patients without typical clinical or electrocardiographic signs of acute myocardial infarction within 48 h after successful resuscitation from out-of-hospital cardiac arrest. Scintigraphic evidence of acute necrosis was present in 23/57 patients (40%). Increased 99mTc-PYP uptake in the pericardial tissue was found in 24 patients (42%). Maximal creatine kinase (CK) concentration was increased in 50/57 patients (88%). CK-MB activity averaged 68+/-52 U/l in patients with positive and 17+/-13 U/l in patients with negative tomograms (P<0.0005), demonstrating the validity of 201Tl/99mTc-PYP tomography. It may be concluded that simultaneous 201Tl/99mTc-PYP tomography is a valuable tool for evaluation of myocardial necrosis after cardiopulmonary resuscitation including DC countershock. Acute myocardial necrosis, as indicated by scintigraphy, represents a potential trigger for the occurrence of ventricular fibrillation. Therefore, 201Tl/99mTc-PYP tomography can be recommended in order to guide further diagnostic and therapeutic interventions in patients after cardiopulmonary resuscitation in whom the underlying cause of the occurrence of ventricular fibrillation is obscure. PMID:8575479

  15. Draft Genome Sequence of Non-Vibrio parahaemolyticus Acute Hepatopancreatic Necrosis Disease Strain KC13.17.5, Isolated from Diseased Shrimp in Vietnam

    PubMed Central

    Kondo, Hidehiro; Van, Phan Thi; Dang, Lua T.

    2015-01-01

    A strain of Vibrio (KC13.17.5) causing acute hepatopancreatic necrosis disease (AHPND) in shrimp in northern Vietnam was isolated. Normally, AHPND is caused by Vibrio parahaemolyticus, but the genomic sequence of the strain indicated that it belonged to Vibrio harveyi. The sequence data included plasmid-like sequences and putative virulence genes. PMID:26383659

  16. Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-α) pathways.

    PubMed

    Dal Bó, Wladmir; Luiz, Ana Paula; Martins, Daniel F; Mazzardo-Martins, Leidiane; Santos, Adair R S

    2013-10-01

    Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3-300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid-induced nociception, with ID₅₀ values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID₅₀ of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-α. Thus, eugenol could represent an important compound in the treatment for acute pain. PMID:22775297

  17. Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha.

    PubMed

    van Miert, A S; van Duin, C T; Wensing, T

    1992-12-01

    Tumour necrosis factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia coli (E. coli) derived human (r.HuTNF-alpha) and bovine TNF (r.BoTNF-alpha) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and compared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 microgram/kg i.v.). Following a single injection of 4 micrograms/kg of r.BoTNF-alpha, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and neutropenia followed by neutrophilia. The i.v. administration of a single injection of 4 micrograms/kg r.HuTNF-alpha induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasma trace metal concentrations when compared with r.BoTNF-alpha-treated goats. The TNF-alpha-induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF-alpha was significantly shorter than after LPS. Moreover, the r.BoTNF-alpha induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-alpha nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-alpha and LPS could be demonstrated. We conclude that both r.BoTNF-alpha and r.HuTNF-alpha induce many of the physiologic, haematologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r

  18. Complete genome sequence of acute viral necrosis virus associated with massive mortality outbreaks in the Chinese scallop, Chlamys farreri

    PubMed Central

    2013-01-01

    Background Acute viral necrosis virus (AVNV) is the causative agent of a serious disease resulting in high mortality in cultured Chinese scallops, Chlamys farreri. We have sequenced and analyzed the complete genome of AVNV. Results The AVNV genome is a linear, double-stranded DNA molecule of 210,993 bp with a nucleotide composition of 38.5% G + C. A total of 123 open reading frames were predicted to encode functional proteins, ranging from 41 to 1,878 amino acid residues. The DNA sequence of AVNV is 97% identical to that of ostreid herpesvirus 1 (OsHV-1), and the amino acid sequences of the encoded proteins of these two viruses are 94-100% identical. The genomic organization of AVNV is similar to that of OsHV-1, and consists of two unique regions (170.4 kb and 3.4 kb, respectively), each flanked by two inverted repeats (7.6 kb and 10.2 kb, respectively), with a third unique region (1.5 kb) situated between the two internal repeats. Conclusions Our results indicate that AVNV is a variant of OsHV-1. The AVNV genome sequence provides information useful for understanding the evolution and divergence of OsHV-1 in marine molluscs. PMID:23566284

  19. Extensive Bone Marrow Necrosis and Osteolytic Lesions in a Case of Acute Myeloid Leukemia Transformed from Polycythemia Vera.

    PubMed

    Chambers, Isaac; Truong, Phu; Kallail, K James; Palko, William

    2016-01-01

    Acute myeloid leukemia (AML) is the most common leukemia in adults. In rare cases, bone marrow necrosis (BMN) and osteolytic lesions are presenting features of AML. The following case describes a patient with known polycythemia vera (PV) that presented with signs of multiple myeloma, including hypercalcemia, anemia, and lytic lesions of the thoracic spine and skull. Laboratory workup was not indicative of myeloma. A bone marrow biopsy was performed, which revealed extensive BMN and initial pathology was consistent with metastatic carcinoma. However, no immunohistochemical stains could be performed due to the extent of BMN; a repeat biopsy was therefore performed. Flow cytometry and CD45 staining were consistent with PV that had transformed to AML. Due to the patient's comorbidities, she was a poor candidate for stem cell transplant and did not wish to pursue chemotherapy. Ultimately, she pursued hospice care. Based on our literature review, both BMN and osteolytic lesions are rare manifestations of AML and have not been reported to occur simultaneously. These findings can lead to a diagnostic dilemma and suspicion of other malignancies. This case demonstrates that AML should remain in the differential diagnosis in those patients who present with BMN and osteolytic lesions. PMID:27433418

  20. Extensive Bone Marrow Necrosis and Osteolytic Lesions in a Case of Acute Myeloid Leukemia Transformed from Polycythemia Vera

    PubMed Central

    Truong, Phu; Kallail, K. James; Palko, William

    2016-01-01

    Acute myeloid leukemia (AML) is the most common leukemia in adults. In rare cases, bone marrow necrosis (BMN) and osteolytic lesions are presenting features of AML. The following case describes a patient with known polycythemia vera (PV) that presented with signs of multiple myeloma, including hypercalcemia, anemia, and lytic lesions of the thoracic spine and skull. Laboratory workup was not indicative of myeloma. A bone marrow biopsy was performed, which revealed extensive BMN and initial pathology was consistent with metastatic carcinoma. However, no immunohistochemical stains could be performed due to the extent of BMN; a repeat biopsy was therefore performed. Flow cytometry and CD45 staining were consistent with PV that had transformed to AML. Due to the patient’s comorbidities, she was a poor candidate for stem cell transplant and did not wish to pursue chemotherapy. Ultimately, she pursued hospice care. Based on our literature review, both BMN and osteolytic lesions are rare manifestations of AML and have not been reported to occur simultaneously. These findings can lead to a diagnostic dilemma and suspicion of other malignancies. This case demonstrates that AML should remain in the differential diagnosis in those patients who present with BMN and osteolytic lesions.  PMID:27433418

  1. Successful Resolution of Gastric Outlet Obstruction Caused by Pancreatic Pseudocyst or Walled-Off Necrosis After Acute Pancreatitis

    PubMed Central

    Zhang, Yun; Zhang, Shao-Yang; Gao, Shun-Liang; Liang, Zhong-Yan; Yu, Wen-Qiao; Liang, Ting-Bo

    2015-01-01

    Objective Delayed gastric emptying (DGE) in patients with acute pancreatitis (AP) can be caused by gastroparesis or gastric outlet obstruction, which may occur when pancreatic pseudocyst (PP) or walled-off necrosis (WON) compresses the stomach. The aim of the study was to explore a proper surgical treatment. Methods From June 2010 to June 2013, 25 of 148 patients with AP suffered DGE. Among them, 12 were caused by gastroparesis, 1 was a result of obstruction from a Candida albicans plug, and 12 were gastric outlet obstruction (GOO) compressed by PP (n = 8) or WON (n = 4), which were treated by percutaneous catheter drainage (PCD). Results All 12 cases of compressing GOO achieved resolution by PCD after 6 [1.86] and 37.25 [12.02] days for PP and WON, respectively. Five cases developed intracystic infection, 3 cases had pancreatic fistulae whereas 2 achieved resolution and 1 underwent a pseudocyst jejunostomy. Conclusions Gastric outlet obstruction caused by a PP or WON is a major cause of DGE in patients with AP. Percutaneous catheter drainage with multiple sites, large-bore tubing, and lavage may be a good therapy due to high safety and minimal invasiveness. PMID:26465954

  2. High-Quality Draft Genomes of Two Vibrio parahaemolyticus Strains Aid in Understanding Acute Hepatopancreatic Necrosis Disease of Cultured Shrimps in Mexico

    PubMed Central

    Noriega-Orozco, Lorena; Sotelo-Mundo, Rogerio R.; Cantu-Robles, Vito A.; Cobian-Guemes, Ana G.; Cota-Verdugo, Rosario G.; Gamez-Alejo, Luis A.; del Pozo-Yauner, Luis; Guevara-Hernandez, Eduardo; Garcia-Orozco, Karina D.; Lopez-Zavala, Alonso A.

    2014-01-01

    The high-quality draft genomes of two Vibrio parahaemolyticus strains, one that causes the acute hepatopancreatic necrosis disease (AHPND) in cultured shrimps (FIM-S1708+), and another that does not (FIM-S1392−) are reported. A chromosome-scale assembly for the FIM-S1392− genome is reported here. The analysis of the two genomes gives some clues regarding the genomic differences between the strains. PMID:25125645

  3. A case report of the use of nanocrystalline silver dressing in the management of acute surgical site wound infected with MRSA to prevent cutaneous necrosis following revision surgery.

    PubMed

    Bhattacharyya, Mayukh; Bradley, Helen

    2008-03-01

    The authors report the use of nanocrystalline silver (Acticoat 7, Smith and Nephew, London, UK) in an acute surgical wound to prevent localized skin necrosis due to infection, thereby avoiding skin grafting as a secondary procedure. Two patients were successfully treated with Acticoat 7 dressings without using systemic antimicrobials after developing methicillin-resistant Staphylococcus aureus infection in the surgical site. Despite a history of smoking and incision through scar tissues, the wound did not progress into deep infection nor was there recurrence of infection at 2 years follow-up. The intention was to use this particular dressing to assess the effect of silver on infected keratinocytes in an acute wound environment. It is possible that the use of Acticoat 7 may reduce the bacterial loading at the wound site, thereby decreasing a propensity for skin necrosis caused by the infective process. This case report demonstrates that the acute surgical wound with impending cutaneous necrosis due to localized infection may be treated without oral antimicrobials. PMID:18372271

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

    PubMed

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

    2014-03-01

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

  5. Alterations in glomerular and tubular dynamics at 1 and 14 days simulated microgravity and after acute return to orthostasis

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.; Mendonca, Margarida M.

    1995-01-01

    Head-down tilt (HDT) is utilized to simulate microgravity and produces a cephalad fluid shift, which results in alterations in fluid and electrolyte balance. These changes in volume homeostasis are due, in part, to alterations in multiple volume control mechanisms in which renal function is a major participant. We have previously demonstrated that glomerular filtration rate increases early in HDT and eventually returns to values not different from non-tilt measurements. This early increase in glomerular filtration rate was also demonstrated during days 2 and 8 of the SLS-1 mission. However, urine flow and electrolyte excretion does not parallel the alternations in glomerular filtration rate and the site of this change in nephron fluid reabsorption pattern has not been previously examined. Through determination of the location of alterations in tubular fluid reabsorption within the nephron, a more detailed hypothesis can be forwarded as to which specific neuro-humoral agents participating in control or renal function in microgravity conditions. the importance of this type of examination is that measurements in circulating neuro-humoral agents and urinary excretion patterns alone are not accurate predictors of how renal functional response may alter to head-down tilt or other models of simulated weightlessness. To examine this issue, renal micropuncture techniques were utilized in Munich-Wistar rats submitted 24 hour and 14 day head-down tilt, measuring all the determinants of glomerular ultrafiltration and obtaining data regarding segmental tubular fluid reabsorption. Following these measurements, the rats were returned to an orthostatic position and after 60 minutes, the measurements were repeated.

  6. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α–Mediated Apoptosis

    PubMed Central

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W.; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N.; Gonzalez, Frank J.

    2016-01-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics–pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factor α (TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics–pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL’s protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  7. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α-Mediated Apoptosis.

    PubMed

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N; Gonzalez, Frank J; Wang, Guangji; Hao, Haiping

    2016-05-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factorα(TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics-pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL's protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  8. Gastrointestinal Fistulas in Acute Pancreatitis With Infected Pancreatic or Peripancreatic Necrosis: A 4-Year Single-Center Experience.

    PubMed

    Jiang, Wei; Tong, Zhihui; Yang, Dongliang; Ke, Lu; Shen, Xiao; Zhou, Jing; Li, Gang; Li, Weiqin; Li, Jieshou

    2016-04-01

    Gastrointestinal (GI) fistula is a well-recognized complication of acute pancreatitis (AP). However, it has been reported in limited literature. This study aimed to evaluate the incidence and outcome of GI fistulas in AP patients complicated with infected pancreatic or peripancreatic necrosis (IPN).Between 2010 and 2013 AP patients with IPN who diagnosed with GI fistula in our center were analyzed in this retrospective study. And we also conducted a comparison between patients with and without GI fistula regarding the baseline characteristics and outcomes.Over 4 years, a total of 928 AP patients were admitted into our center, of whom 119 patients with IPN were diagnosed with GI fistula and they developed 160 GI fistulas in total. Colonic fistula found in 72 patients was the most common form of GI fistula followed with duodenal fistula. All duodenal fistulas were managed by nonsurgical management. Ileostomy or colostomy was performed for 44 (61.1%) of 72 colonic fistulas. Twenty-one (29.2%) colonic fistulas were successfully treated by percutaneous drainage or continuous negative pressure irrigation. Mortality of patients with GI fistula did not differ significantly from those without GI fistula (28.6% vs 21.9%, P = 0.22). However, a significantly higher mortality (34.7%) was observed in those with colonic fistula.GI fistula is a common finding in patients of AP with IPN. Most of these fistulas can be successfully managed with different procedures depending on their sites of origin. Colonic fistula is related with higher mortality than those without GI fistula. PMID:27057908

  9. Sodium hypochlorite-induced acute kidney injury.

    PubMed

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

    2014-03-01

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

  10. Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes.

    PubMed

    Modena, B D; Kurian, S M; Gaber, L W; Waalen, J; Su, A I; Gelbart, T; Mondala, T S; Head, S R; Papp, S; Heilman, R; Friedewald, J J; Flechner, S M; Marsh, C L; Sung, R S; Shidban, H; Chan, L; Abecassis, M M; Salomon, D R

    2016-07-01

    Interstitial fibrosis and tubular atrophy (IFTA) is found in approximately 25% of 1-year biopsies posttransplant. It is known that IFTA correlates with decreased graft survival when histological evidence of inflammation is present. Identifying the mechanistic etiology of IFTA is important to understanding why long-term graft survival has not changed as expected despite improved immunosuppression and dramatically reduced rates of clinical acute rejection (AR) (Services UDoHaH. http://www.ustransplant.org/annual_reports/current/509a_ki.htm). Gene expression profiles of 234 graft biopsy samples were obtained with matching clinical and outcome data. Eighty-one IFTA biopsies were divided into subphenotypes by degree of histological inflammation: IFTA with AR, IFTA with inflammation, and IFTA without inflammation. Samples with AR (n = 54) and normally functioning transplants (TX; n = 99) were used in comparisons. A novel analysis using gene coexpression networks revealed that all IFTA phenotypes were strongly enriched for dysregulated gene pathways and these were shared with the biopsy profiles of AR, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. These molecular biopsy profiles correlated with future graft loss in IFTA samples without inflammation. PMID:26990570

  11. Proximal renal tubular acidosis

    MedlinePlus

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  12. Nonapoptotic cell death in acute kidney injury and transplantation.

    PubMed

    Linkermann, Andreas

    2016-01-01

    Acute tubular necrosis causes a loss of renal function, which clinically presents as acute kidney failure (AKI). The biochemical signaling pathways that trigger necrosis have been investigated in detail over the past 5 years. It is now clear that necrosis (regulated necrosis, RN) represents a genetically driven process that contributes to the pathophysiology of AKI. RN pathways such as necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-induced regulated necrosis (MPT-RN) may be mechanistically distinct, and the relative contributions to overall organ damage during AKI in living organisms largely remain elusive. In a synchronized manner, some necrotic programs induce the breakdown of tubular segments and multicellular functional units, whereas others are limited to killing single cells in the tubular compartment. Importantly, the means by which a renal cell dies may have implications for the subsequent inflammatory response. In this review, the recent advances in the field of renal cell death in AKI and key enzymes that might serve as novel therapeutic targets will be discussed. As a consequence of the interference with RN, the immunogenicity of dying cells in AKI in renal transplants will be diminished, rendering inhibitors of RN indirect immunosuppressive agents. PMID:26759047

  13. Endocytotic Uptake of Zoledronic Acid by Tubular Cells May Explain Its Renal Effects in Cancer Patients Receiving High Doses of the Compound

    PubMed Central

    Verhulst, Anja; Sun, Shuting; McKenna, Charles E.; D’Haese, Patrick C.

    2015-01-01

    Zoledronic acid, a highly potent nitrogen-containing bisphosphonate used for the treatment of pathological bone loss, is excreted unmetabolized via the kidney if not bound to the bone. In cancer patients receiving high doses of the compound renal excretion may be associated with acute tubular necrosis. The question of how zoledronic acid is internalized by renal tubular cells has not been answered until now. In the current work, using a primary human tubular cell culture system, the pathway of cellular uptake of zoledronic acid (fluorescently/radiolabeled) and its cytotoxicity were investigated. Previous studies in our laboratory have shown that this primary cell culture model consistently mimics the physiological characteristics of molecular uptake/transport of the epithelium in vivo. Zoledronic acid was found to be taken up by tubular cells via fluid-phase-endocytosis (from apical and basolateral side) as evidenced by its co-localization with dextran. Cellular uptake and the resulting intracellular level was twice as high from the apical side compared to the basolateral side. Furthermore, the intracellular zoledronic acid level was found to be dependent on the administered concentration and not saturable. Cytotoxic effects however, were only seen at higher administration doses and/or after longer incubation times. Although zoledronic acid is taken up by tubular cells, no net tubular transport could be measured. It is concluded that fluid-phase-endocytosis of zoledronic acid and cellular accumulation at high doses may be responsible for the acute tubular necrosis observed in some cancer patients receiving high doses of the compound. PMID:25756736

  14. Failure to visualize acutely injured kidneys with technetium-99m DMSA does not preclude recoverable function

    SciTech Connect

    Taylor, A. Jr.; Akiya, F.; Gregory, M.C.

    1986-03-01

    A 35-yr-old patient developed severe acute tubular necrosis requiring hemodialysis. A (99mTc)dimercaptosuccinic acid scan of the kidneys showed no renal uptake at 4 or 24 hr, but the patient subsequently recovered normal renal function as judged by a normal serum creatinine. Based on this case report and a review of the literature, one cannot assume irreversible loss of function in patients with acute renal failure, based on the absence of radiopharmaceutical uptake by the kidneys.

  15. Tubular von Hippel-Lindau Knockout Protects against Rhabdomyolysis-Induced AKI

    PubMed Central

    Fähling, Michael; Mathia, Susanne; Paliege, Alexander; Koesters, Robert; Mrowka, Ralf; Peters, Harm; Persson, Pontus Börje; Neumayer, Hans-Hellmut; Bachmann, Sebastian

    2013-01-01

    Renal hypoxia occurs in AKI of various etiologies, but adaptation to hypoxia, mediated by hypoxia-inducible factor (HIF), is incomplete in these conditions. Preconditional HIF activation protects against renal ischemia-reperfusion injury, yet the mechanisms involved are largely unknown, and HIF-mediated renoprotection has not been examined in other causes of AKI. Here, we show that selective activation of HIF in renal tubules, through Pax8-rtTA–based inducible knockout of von Hippel-Lindau protein (VHL-KO), protects from rhabdomyolysis-induced AKI. In this model, HIF activation correlated inversely with tubular injury. Specifically, VHL deletion attenuated the increased levels of serum creatinine/urea, caspase-3 protein, and tubular necrosis induced by rhabdomyolysis in wild-type mice. Moreover, HIF activation in nephron segments at risk for injury occurred only in VHL-KO animals. At day 1 after rhabdomyolysis, when tubular injury may be reversible, the HIF-mediated renoprotection in VHL-KO mice was associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal, as demonstrated by quantitative PCR, pathway enrichment analysis, and immunohistochemistry. In conclusion, a HIF-mediated shift toward improved energy supply may protect against acute tubular injury in various forms of AKI. PMID:23970125

  16. Tubular Coupling

    NASA Technical Reports Server (NTRS)

    Rosenbaum, Bernard J. (Inventor)

    2000-01-01

    A system for coupling a vascular overflow graft or cannula to a heart pump. A pump pipe outlet is provided with an external tapered surface which receives the end of a compressible connula. An annular compression ring with a tapered internal bore surface is arranged about the cannula with the tapered internal surface in a facing relationship to the external tapered surface. The angle of inclination of the tapered surfaces is converging such that the spacing between the tapered surfaces decreases from one end of the external tapered surface to the other end thereby providing a clamping action of the tapered surface on a cannula which increases as a function of the length of cannula segment between the tapered surfaces. The annular compression ring is disposed within a tubular locking nut which threadedly couples to the pump and provides a compression force for urging the annular ring onto the cannula between the tapered surfaces. The nut has a threaded connection to the pump body. The threaded coupling to the pump body provides a compression force for the annular ring. The annular ring has an annular enclosure space in which excess cannula material from the compression between the tapered surfaces to "bunch up" in the space and serve as an enlarged annular ring segment to assist holding the cannula in place. The clamped cannula provides a seamless joint connection to the pump pipe outlet where the clamping force is uniformly applied to the cannula because of self alignment of the tapered surfaces. The nut can be easily disconnected to replace the pump if necessary.

  17. Nuclear medicine in acute and chronic renal failure

    SciTech Connect

    Sherman, R.A.; Byun, K.J.

    1982-07-01

    The diagnostic value of renal scintiscans in patients with acute or chronic renal failure has not been emphasized other than for the estimation of renal size. /sup 131/I OIH, /sup 67/gallium, /sup 99m/TcDTPA, glucoheptonate and DMSA all may be valuable in a variety of specific settings. Acute renal failure due to acute tubular necrosis, hepatorenal syndrome, acute interstitial nephritis, cortical necrosis, renal artery embolism, or acute pyelonephritis may be recognized. Data useful in the diagnosis and management of the patient with obstructive or reflux nephropathy may be obtained. Radionuclide studies in patients with chronic renal failure may help make apparent such causes as renal artery stenosis, chronic pyelonephritis or lymphomatous kidney infiltration. Future correlation of scanning results with renal pathology promises to further expand nuclear medicine's utility in the noninvasive diagnosis of renal disease.

  18. Renin and Acute Renal Failure: Studies in Man

    PubMed Central

    Brown, J. J.; Gleadle, R. I.; Lawson, D. H.; Lever, A. F.; Linton, A. L.; Macadam, R. F.; Prentice, E.; Robertson, J. I. S.; Tree, M.

    1970-01-01

    Plasma renin concentration was increased, usually appreciably, in 22 out of 25 patients with acute renal failure, the average value being 226 units/litre (mean for normal subjects 8·2 units/1.). The highest renin values were found in the first 10 days of the disease; lower and sometimes normal values were found subsequently. Unequivocal acute tubular necrosis was present in only two of the eight cases examined post mortem. These findings are compatible with Goormaghtigh's proposal that an excess of renin and angiotensin may act within the kidney to produce acute renal failure. PMID:4313590

  19. Enhanced cortisol increase upon awakening is associated with greater pain ratings but not salivary cortisol or soluble tumor necrosis factor-α receptor II responses to acute pain

    PubMed Central

    Goodin, Burel R.; Quinn, Noel B.; King, Christopher D.; Page, Gayle G.; Haythornthwaite, Jennifer A.; Edwards, Robert R.; Stapleton, Laura M.; McGuire, Lynanne

    2011-01-01

    Objectives The cortisol awakening response (CAR) is related with psychosocial factors and health in potentially significant ways, suggesting that it may be a distinctive marker of hypothalamic-pituitary-adrenal (HPA) axis function and dysfunction. This sought to expand upon previous work that examined the association between CAR and ratings of laboratory-evoked acute pain stimulation. In addition to evoked pain ratings, this study also tested whether CAR was prospectively related with salivary cortisol and soluble tumor necrosis factor-α receptor II (sTNFαRII) responses to acute pain stimulation. Methods This study included 36 healthy, pain-free volunteers of both sexes recruited via posted study flyers. Prior to completion of laboratory pain testing, salivary cortisol samples were obtained at home over the course of a single morning according to the following time frame: upon awakening, and 15, 30, and 60 min after awakening. Following collection of saliva, study participants brought their home saliva samples to the laboratory for assay and subsequently completed acute experimental pain testing procedures. Results Cluster analysis of CAR revealed two distinct groups with similar patterns of cortisol response to awakening; increased and flattened. Relative to flattened CAR, increased CAR was associated with greater ratings of pain intensity and unpleasantness. Salivary cortisol was significantly increased and sTNFαRII significantly decreased following pain testing, but neither of these responses differed as a function of increased versus flattened CAR. Discussion CAR may be a marker for stress sensitivity and/or the anticipation of impending stress, which could explain why the increased CAR cohort reported greater acute pain ratings. PMID:21904196

  20. Chicken amyloid arthropathy: serum amyloid A, interleukin-1beta, interleukin-6, tumour necrosis factor-alpha and nitric oxide profile in acute phase (12th hour).

    PubMed

    Sevimli, A; Bülbül, T; Bülbül, A; Yagci, A

    2013-01-01

    Acute phase response (APR) is part of the early defense system, which is triggered by different stimuli including, infection, trauma, stres, inflammation and neoplasia. The APR complex is a reaction which induces homeostasis and recovery. In this research, serum amyloid A (SAA), interlaukin (IL)-1beta, IL-6, tumour necrosis factor alpha (TNF-alpha) and nitric oxide (NO) levels were measured 12 hours following injection. For this purpose, Thirty-two 5 weeks old laying chicken were allocated into four groups and intra-articular injections of Freund's adjuvant were used to induce amylod arthropathy in Groups II, III and IV. Vitamin A in group II, and methylprednisolone in group IV were added to enhance and to reduce the severity of amyloidosis, respectively. At the end of the research, it was observed that TNF-alpha and NO increased significantly (P < 0.05) in vitamin A and methylprednisolone groups whereas SAA decreased significantly (P < 0.05) in all groups. It was also observed that IL-6 increased (P < 0.05) in vitamin A group and decreased in all other gorups however, IL-1beta decreased in vitamin A and methylprednisolone groups, while it was increased in the control group. The results of this study suggest that there is a positive correlation between serum TNF-alpha levels in acute and chronic phase in chickens with amyloid arthropathy. PMID:23971191

  1. Smooth muscle cells of the coronary arterial tunica media express tumor necrosis factor-alpha and proliferate during acute rejection of rabbit cardiac allografts.

    PubMed Central

    Tanaka, H.; Swanson, S. J.; Sukhova, G.; Schoen, F. J.; Libby, P.

    1995-01-01

    Graft coronary arteriosclerosis (GCA) frequently limits the long-term success of cardiac transplantation. The pathogenic mechanisms of and stimuli that provoke GCA remain uncertain. Whatever the initiating factors, deranged control of smooth muscle cells (SMC) proliferation likely contributes to the intimal hyperplasia that produces obstructive lesions. To identify mediators that may contribute to ongoing modulation of SMC functions during acute rejection and to explore the mechanisms of the pathogenesis of graft coronary arteriosclerosis, we studied the kinetics of proliferation and the expression of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory and SMC growth-promoting cytokine, in coronary arterial SMCs in rabbit hearts transplanted heterotopically without immunosuppression. Hearts were harvested at 2 (n = 5), 5 (n = 5), and 8.2 +/- 0.4 (mean +/- SD, n = 5) days after transplantation, just before graft failure as judged clinically. SMC proliferation was assessed by continuous bromodeoxyuridine labeling (BrdU 10 mg/kg/d. s.q.). Whole heart cross sections were stained immunohistochemically with monoclonal antibodies that recognize TNF-alpha, BrdU, and SMCs (muscle alpha-actin). Major epicardial coronary arteries (five to nine profiles in each animal) were evaluated. Histological rejection grades by the International Society for Heart and Lung Transplantation scale at 2, 5, and 10 days were 1.6 +/- 0.9, 2.8 +/- 1.1, and 4.0 +/- 0.0, respectively. Medial SMCs in normal hearts and 2 days after transplant expressed little or no TNF-alpha and displayed negligible BrdU incorporation. At 5 days after transplantation, some medial SMCs stained for TNF-alpha and had a low BrdU labeling index (0.5 +/- 0.8%). At 8.2 days after transplant, almost all medial SMCs expressed TNF-alpha intensely and had a high labeling index (29.8 +/- 8.0%). These results demonstrate that acute rejection activates medial SMCs in coronary arteries to express TNF-alpha and that SMC

  2. Walled-off pancreatic necrosis.

    PubMed

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

    2012-05-01

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

  3. The role of slow and persistent TTX-resistant sodium currents in acute tumor necrosis factor-α-mediated increase in nociceptors excitability

    PubMed Central

    Gudes, Sagi; Barkai, Omer; Caspi, Yaki; Katz, Ben; Lev, Shaya

    2014-01-01

    Tetrodotoxin-resistant (TTX-r) sodium channels are key players in determining the input-output properties of peripheral nociceptive neurons. Changes in gating kinetics or in expression levels of these channels by proinflammatory mediators are likely to cause the hyperexcitability of nociceptive neurons and pain hypersensitivity observed during inflammation. Proinflammatory mediator, tumor necrosis factor-α (TNF-α), is secreted during inflammation and is associated with the early onset, as well as long-lasting, inflammation-mediated increase in excitability of peripheral nociceptive neurons. Here we studied the underlying mechanisms of the rapid component of TNF-α-mediated nociceptive hyperexcitability and acute pain hypersensitivity. We showed that TNF-α leads to rapid onset, cyclooxygenase-independent pain hypersensitivity in adult rats. Furthermore, TNF-α rapidly and substantially increases nociceptive excitability in vitro, by decreasing action potential threshold, increasing neuronal gain and decreasing accommodation. We extended on previous studies entailing p38 MAPK-dependent increase in TTX-r sodium currents by showing that TNF-α via p38 MAPK leads to increased availability of TTX-r sodium channels by partial relief of voltage dependence of their slow inactivation, thereby contributing to increase in neuronal gain. Moreover, we showed that TNF-α also in a p38 MAPK-dependent manner increases persistent TTX-r current by shifting the voltage dependence of activation to a hyperpolarized direction, thus producing an increase in inward current at functionally critical subthreshold voltages. Our results suggest that rapid modulation of the gating of TTX-r sodium channels plays a major role in the mediated nociceptive hyperexcitability of TNF-α during acute inflammation and may lead to development of effective treatments for inflammatory pain, without modulating the inflammation-induced healing processes. PMID:25355965

  4. Silencer of Death Domains Controls Cell Death through Tumour Necrosis Factor-Receptor 1 and Caspase-10 in Acute Lymphoblastic Leukemia

    PubMed Central

    Khan, Naveed I.; Welschinger, Robert; Basnett, Jordan; Fung, Carina; Rizos, Helen; Bradstock, Kenneth F.; Bendall, Linda J.

    2014-01-01

    Resistance to apoptosis remains a significant problem in drug resistance and treatment failure in malignant disease. NO-aspirin is a novel drug that has efficacy against a number of solid tumours, and can inhibit Wnt signaling, and although we have shown Wnt signaling to be important for acute lymphoblastic leukemia (ALL) cell proliferation and survival inhibition of Wnt signaling does not appear to be involved in the induction of ALL cell death. Treatment of B lineage ALL cell lines and patient ALL cells with NO-aspirin induced rapid apoptotic cell death mediated via the extrinsic death pathway. Apoptosis was dependent on caspase-10 in association with the formation of the death-inducing signaling complex (DISC) incorporating pro-caspase-10 and tumor necrosis factor receptor 1 (TNF-R1). There was no measurable increase in TNF-R1 or TNF-α in response to NO-aspirin, suggesting that the process was ligand-independent. Consistent with this, expression of silencer of death domain (SODD) was reduced following NO-aspirin exposure and lentiviral mediated shRNA knockdown of SODD suppressed expansion of transduced cells confirming the importance of SODD for ALL cell survival. Considering that SODD and caspase-10 are frequently over-expressed in ALL, interfering with these proteins may provide a new strategy for the treatment of this and potentially other cancers. PMID:25061812

  5. Genetic diversity of Vibrio parahaemolyticus strains isolated from farmed Pacific white shrimp and ambient pond water affected by acute hepatopancreatic necrosis disease outbreak in Thailand.

    PubMed

    Chonsin, Kaknokrat; Matsuda, Shigeaki; Theethakaew, Chonchanok; Kodama, Toshio; Junjhon, Jiraphan; Suzuki, Yasuhiko; Suthienkul, Orasa; Iida, Tetsuya

    2016-01-01

    Acute hepatopancreatic necrosis disease (AHPND) is an emerging shrimp disease that causes massive die-offs in farmed shrimps. Recent outbreaks of AHPND in Asia have been causing great losses for shrimp culture and have become a serious socioeconomic problem. The causative agent of AHPND is Vibrio parahaemolyticus, which is typically known to cause food-borne gastroenteritis in humans. However, there have been few reports of the epidemiology of V. parahaemolyticus AHPND strains, and the genetic relationship among AHPND strains is unclear. Here, we report the genetic characterization of V. parahaemolyticus strains isolated from AHPND outbreaks in Thailand. We found eight isolates from AHPND-suspected shrimps and pond water that were positive for AHPND markers AP1 and AP2. PCR analysis confirmed that none of these eight AP-positive AHPND strains possesses the genes for the conventional virulence factors affecting to humans, such as thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH) and type III secretion system 2. Phylogenetic analysis by multilocus sequence typing showed that the AHPND strains are genetically diverse, suggesting that AHPND strains were not derived from a single genetic lineage. Our study represents the first report of molecular epidemiology of AHPND-causing V. parahaemolyticus strains using multilocus sequence typing, and provides an insight into their evolutionary mechanisms. PMID:26590959

  6. Comparison of Ranson, Glasgow, MOSS, SIRS, BISAP, APACHE-II, CTSI Scores, IL-6, CRP, and Procalcitonin in Predicting Severity, Organ Failure, Pancreatic Necrosis, and Mortality in Acute Pancreatitis

    PubMed Central

    Khanna, Ajay K.; Meher, Susanta; Prakash, Shashi; Tiwary, Satyendra Kumar; Singh, Usha; Srivastava, Arvind; Dixit, V. K.

    2013-01-01

    Background. Multifactorial scorings, radiological scores, and biochemical markers may help in early prediction of severity, pancreatic necrosis, and mortality in patients with acute pancreatitis (AP). Methods. BISAP, APACHE-II, MOSS, and SIRS scores were calculated using data within 24 hrs of admission, whereas Ranson and Glasgow scores after 48 hrs of admission; CTSI was calculated on day 4 whereas IL-6 and CRP values at end of study. Predictive accuracy of scoring systems, sensitivity, specificity, and positive and negative predictive values of various markers in prediction of severe acute pancreatitis, organ failure, pancreatic necrosis, admission to intensive care units and mortality were calculated. Results. Of 72 patients, 31 patients had organ failure and local complication classified as severe acute pancreatitis, 17 had pancreatic necrosis, and 9 died (12.5%). Area under curves for Ranson, Glasgow, MOSS, SIRS, APACHE-II, BISAP, CTSI, IL-6, and CRP in predicting SAP were 0.85, 0.75, 0.73, 0.73, 0.88, 0.80, 0.90, and 0.91, respectively, for pancreatic necrosis 0.70, 0.64, 0.61, 0.61, 0.68, 0.61, 0.75, 0.86, and 0.90, respectively, and for mortality 0.84, 0.83, 0.77, 0.76, 0.86, 0.83, 0.57, 0.80, and 0.75, respectively. Conclusion. CRP and IL-6 have shown a promising result in early detection of severity and pancreatic necrosis whereas APACHE-II and Ranson score in predicting AP related mortality in this study. PMID:24204087

  7. Time profile of viral DNA in aqueous humor samples of patients treated for varicella-zoster virus acute retinal necrosis by use of quantitative real-time PCR.

    PubMed

    Bernheim, D; Germi, R; Labetoulle, M; Romanet, J P; Morand, P; Chiquet, C

    2013-07-01

    The objective of this study was to evaluate the kinetics of varicella-zoster virus (VZV) loads using quantitative PCR (qPCR) in patients treated for acute retinal necrosis (ARN). Six patients (52 ± 13 years old) with ARN syndrome were consecutively studied. Aqueous humor (AH) was sampled from both eyes of all patients for qPCR evaluation. The patients were treated with intravenous acyclovir and intravitreal injections of antiviral drugs. The mean follow-up time was 17.6 ± 16.4 months. Main outcome measures were the numbers of viral genome copies in the AH, assessed using real-time qPCR with hydrolysis probe technology with a threshold of detection of 200 copies/ml. Two main portions of the viral load curves were observed for each patient: a plateau phase (27.8 ± 24.9 days) and a decrease in the number of viral genome copies. The mean baseline viral load was 3.4 × 10(7) ± 4.45 × 10(7) copies/ml (6 × 10(6) to 1.2 × 10(8) copies/ml). The viral load decreased according to a logarithmic model, with a 50% reduction obtained in 3 ± 0.7 days. There was a significant viral load (>102 copies/ml) at 50 days after the onset of treatment, despite antiviral drugs. qPCR use demonstrated reproducible VZV DNA kinetics with a two-phase evolution: a plateau followed by a logarithmic decrease. These data suggest that high-dosage antiviral therapy administered for the conventional 10-day duration is insufficient for most patients. This series of patients responded with a similar decrease in viral load once treatment was initiated, and the data from these patients may be used to predict the responses of future patients. PMID:23637296

  8. Genetic Variations of Tumor Necrosis Factor –α-308 and Lymphtoxin-α+252 in Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia Patients

    PubMed Central

    Nasiri, Hajar; Farajnia, Safar; Rezamand, Azim; MovassaghPour, Ali Akbar; Esmaeili, Heydar Ali; Monfaredan, Amir; Mobarra, Naser; Rahimifar, Nasser; Sahebi, Leyla; Farshdousti Hagh, Majid

    2013-01-01

    Objective(s): Non- Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL) are two main hematological malignances which have been driven from lymphoid tissue. Genetic polymorphisms in tumor necrosis factor-α (TNF-α) -308 and lymphotoxin-α (LT-α) +252 may affect their transcription and expression which leads to their high plasma level. The frequency of the TNF-α (-308) and LT-α (+ 252) polymorphisms are different for NHL and ALL cases in various populations with different ethnicity. This research is designed to investigate the prevalence and association of TNF-α (-308) and LT-α (+ 252) polymorphisms from NHL and ALL in Azarian patients and healthy individuals from Northwestern part of Iran. Materials and Methods: Seventy subjects with ALL and 68 NHL, along with another 130 healthy subjects as control group took part in this study. Genomic DNA was extracted, then genetic polymorphisms in TNF-α and LT-α genes were analyzed with the PCR-RFLP and NCOI as restriction enzyme. A statistical analysis was performed by chi-square test using SPSS software. A P-value of <0.05 was considered statistically significant. Results: A statistically significant difference of LT-α polymorphism was in NHL patients and control (P-value= 0.008) but there was not any association of TNF-α polymorphism between NHL patients and control group. A significant association for TNF-a variant was in ALL and control (P-value =0.005), however, there was no relationship about LT variant between ALL and control. Conclusion: The results show that there are significant differences between TNF-α (-308) and LT-α (+252) genetic polymorphisms respectively in ALL and NHL patients with control group from Northwestern part of Iran. PMID:24171078

  9. C1q/Tumor Necrosis Factor-Related Protein 9 Protects against Acute Myocardial Injury through an Adiponectin Receptor I-AMPK-Dependent Mechanism.

    PubMed

    Kambara, Takahiro; Shibata, Rei; Ohashi, Koji; Matsuo, Kazuhiro; Hiramatsu-Ito, Mizuho; Enomoto, Takashi; Yuasa, Daisuke; Ito, Masanori; Hayakawa, Satoko; Ogawa, Hayato; Aprahamian, Tamar; Walsh, Kenneth; Murohara, Toyoaki; Ouchi, Noriyuki

    2015-06-01

    Obesity is a risk factor for cardiovascular disease. C1q/tumor necrosis factor-related protein 9 (CTRP9) is an adipokine that is downregulated by obesity. We investigated the role of CTRP9 in cardiac injury with loss-of-function genetic manipulations and defined the receptor-mediated signaling pathway downstream of this adipokine. CTRP9-knockout (CTRP9-KO) mice at the age of 12 weeks were indistinguishable from wild-type (WT) mice under basal conditions. CTRP9-KO mice had exacerbated contractile left ventricle dysfunction following intraperitoneal injection of lipopolysaccharide (LPS) compared to WT mice. Administration of LPS to CTRP9-KO mice also resulted in increased expression of proinflammatory cytokines and oxidative stress markers in the heart compared to WT mice. Likewise, CTRP9-KO mice showed increased myocardial infarct size and elevated expression of inflammatory mediators in ischemic heart following ischemia and reperfusion compared to WT mice. Treatment of cardiac myocytes with CTRP9 protein led to suppression of LPS-induced expression of proinflammatory genes, which was reversed by blockade of AMPK or ablation of adiponectin receptor I (AdipoR1). Systemic delivery of CTRP9 attenuated LPS-induced cardiac dysfunction in WT mice but not in muscle-specific transgenic mice expressing dominant-negative mutant form of AMPK or in AdipoR1-knockout mice. CTRP9 protects against acute cardiac damage in response to pathological stimuli by suppressing inflammatory reactions through AdipoR1/AMPK-dependent mechanisms. PMID:25870106

  10. Time Profile of Viral DNA in Aqueous Humor Samples of Patients Treated for Varicella-Zoster Virus Acute Retinal Necrosis by Use of Quantitative Real-Time PCR

    PubMed Central

    Bernheim, D.; Germi, R.; Labetoulle, M.; Romanet, J. P.; Morand, P.

    2013-01-01

    The objective of this study was to evaluate the kinetics of varicella-zoster virus (VZV) loads using quantitative PCR (qPCR) in patients treated for acute retinal necrosis (ARN). Six patients (52 ± 13 years old) with ARN syndrome were consecutively studied. Aqueous humor (AH) was sampled from both eyes of all patients for qPCR evaluation. The patients were treated with intravenous acyclovir and intravitreal injections of antiviral drugs. The mean follow-up time was 17.6 ± 16.4 months. Main outcome measures were the numbers of viral genome copies in the AH, assessed using real-time qPCR with hydrolysis probe technology with a threshold of detection of 200 copies/ml. Two main portions of the viral load curves were observed for each patient: a plateau phase (27.8 ± 24.9 days) and a decrease in the number of viral genome copies. The mean baseline viral load was 3.4 × 107 ± 4.45 × 107 copies/ml (6 × 106 to 1.2 × 108 copies/ml). The viral load decreased according to a logarithmic model, with a 50% reduction obtained in 3 ± 0.7 days. There was a significant viral load (>102 copies/ml) at 50 days after the onset of treatment, despite antiviral drugs. qPCR use demonstrated reproducible VZV DNA kinetics with a two-phase evolution: a plateau followed by a logarithmic decrease. These data suggest that high-dosage antiviral therapy administered for the conventional 10-day duration is insufficient for most patients. This series of patients responded with a similar decrease in viral load once treatment was initiated, and the data from these patients may be used to predict the responses of future patients. PMID:23637296

  11. Characterization and PCR Detection Of Binary, Pir-Like Toxins from Vibrio parahaemolyticus Isolates that Cause Acute Hepatopancreatic Necrosis Disease (AHPND) in Shrimp

    PubMed Central

    Sirikharin, Ratchanok; Taengchaiyaphum, Suparat; Sanguanrut, Piyachat; Chi, Thanh Duong; Mavichak, Rapeepat; Proespraiwong, Porranee; Nuangsaeng, Bunlung; Thitamadee, Siripong; Flegel, Timothy W.; Sritunyalucksana, Kallaya

    2015-01-01

    Unique isolates of Vibrio parahaemolyticus (VPAHPND) have previously been identified as the causative agent of acute hepatopancreatic necrosis disease (AHPND) in shrimp. AHPND is characterized by massive sloughing of tubule epithelial cells of the hepatopancreas (HP), proposed to be induced by soluble toxins released from VPAHPND that colonize the shrimp stomach. Since these toxins (produced in broth culture) have been reported to cause AHPND pathology in reverse gavage bioassays with shrimp, we used ammonium sulfate precipitation to prepare protein fractions from broth cultures of VPAHPND isolates for screening by reverse gavage assays. The dialyzed 60% ammonium sulfate fraction caused high mortality within 24–48 hours post-administration, and histological analysis of the moribund shrimp showed typical massive sloughing of hepatopancreatic tubule epithelial cells characteristic of AHPND. Analysis of the active fraction by SDS-PAGE revealed two major bands at marker levels of approximately 16 kDa (ToxA) and 50 kDa (ToxB). Mass spectrometry analysis followed by MASCOT analysis revealed that both proteins had similarity to hypothetical proteins of V. parahaemolyticus M0605 (contig034 GenBank accession no. JALL01000066.1) and similarity to known binary insecticidal toxins called 'Photorhabdus insect related' proteins A and B (Pir-A and Pir-B), respectively, produced by the symbiotic, nematode bacterium Photorhabdus luminescens. In in vivo tests, it was shown that recombinant ToxA and ToxB were both required in a dose dependent manner to cause AHPND pathology, indicating further similarity to Pir-A and -B. A single-step PCR method was designed for detection of the ToxA gene and was validated using 104 bacterial isolates consisting of 51 VPAHPND isolates, 34 non-AHPND VP isolates and 19 other isolates of bacteria commonly found in shrimp ponds (including other species of Vibrio and Photobacterium). The results showed 100% specificity and sensitivity for detection of

  12. Contrast echocardiography in acute myocardial ischemia. III. An in vivo comparison of the extent of abnormal wall motion with the area at risk for necrosis.

    PubMed

    Kaul, S; Pandian, N G; Gillam, L D; Newell, J B; Okada, R D; Weyman, A E

    1986-02-01

    To define the in vivo relation between abnormal wall motion and the area at risk for necrosis after acute coronary occlusion, 11 open chest dogs were studied. Five dogs underwent left anterior descending coronary artery occlusion and six underwent left circumflex artery occlusion. Area at risk was defined at five short-axis levels (mitral valve, chordal, high and low papillary muscle and apex) using myocardial contrast echocardiography. Wall motion was measured in the cycles preceding injection of contrast medium. Two observers used two different methods to measure wall motion. In method A, end-diastolic to end-systolic fractional radial change for each of 32 endocardial targets was determined. The extent of abnormal wall motion was then calculated using three definitions of wall motion abnormality: akinesia/dyskinesia, fractional inward endocardial excursion of less than 10%, and fractional inward endocardial excursion of less than 20%. In method B, the information from the entire systolic contraction sequence was analyzed and correlated with a normal contraction pattern. The best linear correlation between area at risk (AR) and abnormal wall motion (AWM) was achieved using method B and expressed by the following linear regression: AWM = 0.92 AR + 3.0 (r = 0.92, p less than 0.0001, SEE = 1.7%). Of the three definitions of abnormality used in method A, the best correlation was achieved between area at risk and less than 10% inward endocardial excursion and was expressed by the following polynomial regression: AWM = -0.01 AR2 + 1.5 AR -0.14 (r = 0.92, p less than 0.001, SEE = 1.7%). These data demonstrate that there is a definite relation between area at risk and abnormal wall motion but that this relation varies depending on the method used to analyze wall motion. However, wall motion during acute ischemia is also influenced by the loading conditions of the heart. Because these may vary in a manner that is independent of the ischemic process, measurement of both

  13. A supramolecular tubular nanoreactor.

    PubMed

    Li, Zhi-Qiang; Zhang, Ying-Ming; Chen, Yong; Liu, Yu

    2014-07-01

    The extremely strong noncovalent complexation between the rigid host of phthalocyanine-bridged β-cyclodextrins and the amphiphilic guest carboxylated porphyrin is employed to construct a hollow tubular structure as a supramolecular nanoreactor. A representative coupling reaction occurs in the hydrophobic interlayers of the tubular walls in pure water at room temperature, leading to an enhancement of ten times higher reaction rate without any adverse effect on catalytic activity and conversion. PMID:24890802

  14. Interactive toxicity of inorganic mercury and trichloroethylene in rat and human proximal tubules: Effects on apoptosis, necrosis, and glutathione status

    SciTech Connect

    Lash, Lawrence H. . E-mail: l.h.lash@wayne.edu; Putt, David A.; Hueni, Sarah E.; Payton, Scott G.; Zwickl, Joshua

    2007-06-15

    Simultaneous or prior exposure to one chemical may alter the concurrent or subsequent response to another chemical, often in unexpected ways. This is particularly true when the two chemicals share common mechanisms of action. The present study uses the paradigm of prior exposure to study the interactive toxicity between inorganic mercury (Hg{sup 2+}) and trichloroethylene (TRI) or its metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in rat and human proximal tubule. Pretreatment of rats with a subtoxic dose of Hg{sup 2+} increased expression of glutathione S-transferase-{alpha}1 (GST{alpha}1) but decreased expression of GST{alpha}2, increased activities of several GSH-dependent enzymes, and increased GSH conjugation of TRI. Primary cultures of rat proximal tubular (rPT) cells exhibited both necrosis and apoptosis after incubation with Hg{sup 2+}. Pretreatment of human proximal tubular (hPT) cells with Hg{sup 2+} caused little or no changes in GST expression or activities of GSH-dependent enzymes, decreased apoptosis induced by TRI or DCVC, but increased necrosis induced by DCVC. In contrast, pretreatment of hPT cells with TRI or DCVC protected from Hg{sup 2+} by decreasing necrosis and increasing apoptosis. Thus, whereas pretreatment of hPT cells with Hg{sup 2+} exacerbated cellular injury due to TRI or DCVC by shifting the response from apoptosis to necrosis, pretreatment of hPT cells with either TRI or DCVC protected from Hg{sup 2+}-induced cytotoxicity by shifting the response from necrosis to apoptosis. These results demonstrate that by altering processes related to GSH status, susceptibilities of rPT and hPT cells to acute injury from Hg{sup 2+}, TRI, or DCVC are markedly altered by prior exposures.

  15. Djenkol bean poisoning (djenkolism): an unusual cause of acute renal failure.

    PubMed

    Segasothy, M; Swaminathan, M; Kong, N C; Bennett, W M

    1995-01-01

    This report describes a patient with acute renal failure that resulted from the ingestion of djenkol beans. Features of acute djenkolism include nausea, vomiting, bilateral loin pain, gross hematuria, and oliguria. The blood urea level was 16.2 mmol/L and the serum creatinine was 460 mumol/L. Phase contrast microscopy of the urinary sediment indicated that the hematuria was nonglomerular. Ultrasound of the kidneys showed slightly enlarged kidneys with no features of obstruction. Renal biopsy showed acute tubular necrosis similar to the single animal study reported in the literature. With conservative therapy, which included rehydration with normal saline and alkalinization of the urine with sodium bicarbonate, the acute renal failure resolved. Based on its chemistry, djenkol bean-associated acute renal failure may be analogous to acute uric acid nephropathy. PMID:7810535

  16. Acute kidney injury and disseminated intravascular coagulation due to mercuric chloride poisoning.

    PubMed

    Dhanapriya, J; Gopalakrishnan, N; Arun, V; Dineshkumar, T; Sakthirajan, R; Balasubramaniyan, T; Haris, M

    2016-01-01

    Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI) and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (DIC). Renal biopsy showed acute tubular necrosis. Later, the consumed substance was proven to be mercuric chloride. His renal failure improved over time, and his creatinine normalized after 2 months. PMID:27194836

  17. Acute kidney injury and disseminated intravascular coagulation due to mercuric chloride poisoning

    PubMed Central

    Dhanapriya, J.; Gopalakrishnan, N.; Arun, V.; Dineshkumar, T.; Sakthirajan, R.; Balasubramaniyan, T.; Haris, M.

    2016-01-01

    Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI) and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (DIC). Renal biopsy showed acute tubular necrosis. Later, the consumed substance was proven to be mercuric chloride. His renal failure improved over time, and his creatinine normalized after 2 months. PMID:27194836

  18. Computed radionuclide urogram for assessing acute renal failure

    SciTech Connect

    Schlegel, J.U.; Lang, E.K.

    1980-05-01

    The computed radionuclide urogram is advocated as a noninvasive diagnostic method for differentiation of the most common prerenal, renal, and postrenal causes of acute renal failure. On the basis of characteristic changes in the effective renal plasma flow rate, the calculated filtration fraction, and the calculated glomerular filtration rate, prerenal conditions such as renal artery stenosis or thrombosis, renal conditions such as acute rejection or acute tubular necrosis, and postrenal conditions such as obstruction or leakage, which are the most common causes of acute renal failure, can be differentiated. In conjunction with morphologic criteria derived from sonograms, a diagnosis with acceptable confidence can be rendered in most instances. Both the computed radionuclide urogram and sonogram are noninvasive and can be used without adverse effects in the presence of azotemia and even anuria. This also makes feasible reexamination at intervals to assess effect of therapy and offer prognostic information.

  19. Acute renal failure and severe thrombocytopenia associated with metamizole.

    PubMed

    Redondo-Pachon, Maria Dolores; Enriquez, Ricardo; Sirvent, Ana Esther; Millan, Isabel; Romero, Alberto; Amorós, Francisco

    2014-01-01

    Metamizole or dipyrone is a pyrazolone derivative that belongs to the non-steroidal anti-inflammatory drugs. Its main side-effect is hematological toxicity. Thrombocytopenia due to metamizole is rare and is usually associated with the involvement of the two other blood series. Drug-induced thrombocytopenia is more frequently related to immune mechanisms, and the diagnosis is still largely made by exclusion of other causes and by correlation of timing of thrombocytopenia with the administration of drug. Metamizole may cause acute renal failure due to hemodynamic renal failure/acute tubular necrosis and/or acute tubulointerstitial nephritis. We report a case of acute renal failure and severe thrombocytopenia after metamizole. As far as we know, this combination of adverse effects from this drug has not been reported previously. PMID:24434395

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

    PubMed

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

    2016-01-01

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

  1. Westinghouse tubular SOFC technology

    SciTech Connect

    Ray, E.R.

    1992-12-01

    A summary of significant developments and accomplishments which have recently occurred throughout the tubular Solidi Oxide Fuel Cell (SOFC) program include: Demonstration that thousands of tubular solid oxide fuel cells can be fabricated with consistent and reproducible performance. Continuous operation of a 3 kWe tubular SOFC system for over six months at a customer`s test site. Demonstration of stable performance and lifetime in excess of 5,300 hours for a 3 kWe generator module, operating on desulfurized natural gas without external humidification. Demonstration of stable performance and life times in excess of 30,000 hours in multiple single cell tests. Design, construction and operation of a dedicated cell, module and generator Pre-Pilot Manufacturing Facility (PPMF). Successful 6,840 hour bundle tests of 50 cm. cells produced at the PPMF. Significant improvements in cell performance and life and marked reduction in cell degradation. Design, construction and successful operation of a 20 kWe tubular solid oxide fuel cell generator module. Design, construction, shipment and installation of 25 kWe (40 kWe peak power) field units.

  2. Westinghouse tubular SOFC technology

    SciTech Connect

    Ray, E.R.

    1992-01-01

    A summary of significant developments and accomplishments which have recently occurred throughout the tubular Solidi Oxide Fuel Cell (SOFC) program include: Demonstration that thousands of tubular solid oxide fuel cells can be fabricated with consistent and reproducible performance. Continuous operation of a 3 kWe tubular SOFC system for over six months at a customer's test site. Demonstration of stable performance and lifetime in excess of 5,300 hours for a 3 kWe generator module, operating on desulfurized natural gas without external humidification. Demonstration of stable performance and life times in excess of 30,000 hours in multiple single cell tests. Design, construction and operation of a dedicated cell, module and generator Pre-Pilot Manufacturing Facility (PPMF). Successful 6,840 hour bundle tests of 50 cm. cells produced at the PPMF. Significant improvements in cell performance and life and marked reduction in cell degradation. Design, construction and successful operation of a 20 kWe tubular solid oxide fuel cell generator module. Design, construction, shipment and installation of 25 kWe (40 kWe peak power) field units.

  3. Prediction of pancreatic necrosis by dynamic pancreatography.

    PubMed Central

    Bradley, E L; Murphy, F; Ferguson, C

    1989-01-01

    Parenchymal necrosis has recently been recognized as the principal determinant of the incidence of secondary infection in acute pancreatitis. Because secondary infection of pancreatic necrosis accounts for more than 80% of all deaths from acute pancreatitis, a method for determining the presence or absence of parenchymal necrosis would offer considerable prognostic and therapeutic information. Thirty seven patients with unequivocal acute pancreatitis and five normal controls were prospectively studied with intravenous bolus, contrast-enhanced computed tomography (dynamic pancreatography). In the absence of pancreatic necrosis, there were no significant differences in parenchymal enhancement between any of the following patient groups: controls (5), uncomplicated pancreatitis (20), pancreatic abscess (7), or peripancreatic necrosis (4)(p less than 0.05). On the other hand, pancreatic parenchymal enhancement was significantly reduced or absent in all six patients with segmental or diffuse pancreatic necrosis (p less than 0.05). Postcontrast pancreatic parenchymal enhancement was also found to be inversely correlated with the number of Ranson signs (p less than 0.001). Dynamic pancreatography offers prognostic information and is a safe and reliable technique for predicting the presence or absence of pancreatic parenchymal necrosis. Images Figs. 1A and B. Figs. 3A and B. Figs. 4A and B. Fig. 5. Figs. 6A and B. Fig. 7. PMID:2802834

  4. Tubular Secretion in CKD.

    PubMed

    Suchy-Dicey, Astrid M; Laha, Thomas; Hoofnagle, Andrew; Newitt, Rick; Sirich, Tammy L; Meyer, Timothy W; Thummel, Ken E; Yanez, N David; Himmelfarb, Jonathan; Weiss, Noel S; Kestenbaum, Bryan R

    2016-07-01

    Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation. PMID:26614381

  5. Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury

    PubMed Central

    Cocchiaro, Pasquale; Fox, Christopher; Tregidgo, Nicholas W.; Howarth, Rachel; Wood, Katrina M.; Situmorang, Gerhard R.; Pavone, Luigi M.; Sheerin, Neil S.; Moles, Anna

    2016-01-01

    Acute kidney injury (AKI) is an abrupt reduction in kidney function caused by different pathological processes. It is associated with a significant morbidity and mortality in the acute phase and an increased risk of developing End Stage Renal Disease. Despite the progress in the management of the disease, mortality rates in the last five decades remain unchanged at around 50%. Therefore there is an urgent need to find new therapeutic strategies to treat AKI. Lysosomal proteases, particularly Cathepsin D (CtsD), play multiple roles in apoptosis however, their role in AKI is still unknown. Here we describe a novel role for CtsD in AKI. CtsD expression was upregulated in damaged tubular cells in nephrotoxic and ischemia reperfusion (IRI) induced AKI. CtsD inhibition using Pepstatin A led to an improvement in kidney function, a reduction in apoptosis and a decrease in tubular cell damage in kidneys with nephrotoxic or IRI induced AKI. Pepstatin A treatment slowed interstitial fibrosis progression following IRI induced AKI. Renal transplant biopsies with acute tubular necrosis demonstrated high levels of CtsD in damaged tubular cells. These results support a role for CtsD in apoptosis during AKI opening new avenues for the treatment of AKI by targeting lysosomal proteases. PMID:27271556

  6. Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury.

    PubMed

    Cocchiaro, Pasquale; Fox, Christopher; Tregidgo, Nicholas W; Howarth, Rachel; Wood, Katrina M; Situmorang, Gerhard R; Pavone, Luigi M; Sheerin, Neil S; Moles, Anna

    2016-01-01

    Acute kidney injury (AKI) is an abrupt reduction in kidney function caused by different pathological processes. It is associated with a significant morbidity and mortality in the acute phase and an increased risk of developing End Stage Renal Disease. Despite the progress in the management of the disease, mortality rates in the last five decades remain unchanged at around 50%. Therefore there is an urgent need to find new therapeutic strategies to treat AKI. Lysosomal proteases, particularly Cathepsin D (CtsD), play multiple roles in apoptosis however, their role in AKI is still unknown. Here we describe a novel role for CtsD in AKI. CtsD expression was upregulated in damaged tubular cells in nephrotoxic and ischemia reperfusion (IRI) induced AKI. CtsD inhibition using Pepstatin A led to an improvement in kidney function, a reduction in apoptosis and a decrease in tubular cell damage in kidneys with nephrotoxic or IRI induced AKI. Pepstatin A treatment slowed interstitial fibrosis progression following IRI induced AKI. Renal transplant biopsies with acute tubular necrosis demonstrated high levels of CtsD in damaged tubular cells. These results support a role for CtsD in apoptosis during AKI opening new avenues for the treatment of AKI by targeting lysosomal proteases. PMID:27271556

  7. Acute kidney injury associated with androgenic steroids and nutritional supplements in bodybuilders†

    PubMed Central

    Almukhtar, Safa E.; Abbas, Alaa A.; Muhealdeen, Dana N.; Hughson, Michael D.

    2015-01-01

    Four bodybuilders who injected anabolic steroids and ingested commercial protein (78–104 g/day) and creatine (15 g/day) products presented with serum creatinine levels between 229.84 and 335.92 µmol/L (2.6–3.8 mg/dL). Renal biopsies revealed acute tubular necrosis. Four weeks after discontinuing injections and supplements, serum creatinine was in the normal range and estimated glomerular filtration rate > 1.00 mL/s (60 mL/min), including two patients with biopsies showing >30% interstitial fibrosis and tubular atrophy. The findings highlight a risk for acute and potentially chronic kidney injury among young men abusing anabolic steroids and using excessive amounts of nutritional supplements. PMID:26251708

  8. Tubular toxicity of proteinuria.

    PubMed

    Baines, Richard J; Brunskill, Nigel J

    2011-03-01

    Proteinuria is a prognostic indicator of progressive kidney disease and poor cardiovascular outcomes. Abnormally filtered bioactive macromolecules interact with proximal tubular epithelial cells (PTECs), which results in the development of proteinuric nephropathy. This condition is characterized by alterations in PTEC growth, apoptosis, gene transcription and inflammatory cytokine production as a consequence of dysregulated signaling pathways that are stimulated by proteinuric tubular fluid. The megalin-cubilin complex mediates the uptake of several proteins, including albumin, into PTECs. Megalin might also possess intrinsic signaling properties and the ability to regulate cell signaling pathways and gene transcription after processing regulated intramembrane proteolysis. Megalin could, therefore, link abnormal PTEC albumin exposure with altered growth factor receptor activation, proinflammatory and profibrotic signaling, and gene transcription. Evidence now suggests that other PTEC pathways for protein reabsorption of (patho)physiological importance might be mediated by the neonatal Fc receptor and CD36. PMID:21151210

  9. 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. PMID:27048819

  10. Acute kidney injury: A rare cause.

    PubMed

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

    2015-09-01

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

  11. Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

    PubMed

    Tracey, K J; Morgello, S; Koplin, B; Fahey, T J; Fox, J; Aledo, A; Manogue, K R; Cerami, A

    1990-12-01

    We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects. PMID:2254457

  12. Phenazopyridine associated acute interstitial nephritis and review of literature.

    PubMed

    Singh, Manisha; Shailesh, Fnu; Tiwari, Upasana; Sharma, Shree G; Malik, Bilal

    2014-06-01

    Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage. PMID:24575779

  13. Management of Acute-on-Chronic Liver Failure.

    PubMed

    Durand, Francois; Nadim, Mitra K

    2016-05-01

    Acute-on-chronic liver failure (ACLF) is defined by the occurrence of organ failure(s) other than the liver in patients with cirrhosis. Even though mortality rates are high, there should no longer be reluctance to admit patients with ACLF in the intensive care unit. The prevalence of multidrug-resistant bacteria is high and broad spectrum antibiotics should be initiated as soon as infection is suspected. In patients with circulatory failure, the assessment of circulatory status is challenging due to the hyperkinetic state and an imbalance between the splanchnic and systemic blood volume. Acute kidney injury is common in patients with ACLF. Acute tubular necrosis should be differentiated from hepatorenal syndrome, which justifies vasoconstrictive agents. Renal replacement therapy and mechanical ventilation should be decided on clinical grounds. Recent trials on extracorporeal liver support failed to demonstrate a survival benefit. Aggressive management may serve as a bridge to transplantation provided patients are likely to survive after transplantation. PMID:27172356

  14. Renal papillary necrosis

    MedlinePlus

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

  15. [Digital necrosis in hand by uncommon mechanism].

    PubMed

    Leroux, Maria Bibiana; Lashak, Celina; Mazzurco, Martin

    2013-07-01

    A 43-year-old, non-smoking man presented with acute ischemic lesions of his left hand. He had been taking beta-blockers for his arterial hypertension. The day before the occurrence of these acute lesions, he self medicated with a drug containing ergotamine and caffeine because of a headache. About one hour after mild trauma to the hand, he noticed intense cyanosis accompanied by severe pain in the fingers that progressed to digital necrosis. Hematological tests, hand radiography, echo Doppler, and nailfold videocapillaroscopy were performed. Digital necrosis owing to an unusual combination of ischemic mechanisms is assumed. PMID:24010508

  16. L-Aminoacid Oxidase from Bothrops leucurus Venom Induces Nephrotoxicity via Apoptosis and Necrosis

    PubMed Central

    Morais, Isabel C. O.; Pereira, Gustavo J. S.; Orzáez, M.; Jorge, Roberta J. B.; Bincoletto, Claudia; Toyama, Marcos H.; Monteiro, Helena S. A.; Smaili, Soraya S.; Pérez-Payá, Enrique; Martins, Alice M. C.

    2015-01-01

    Acute renal failure is a common complication caused by Bothrops viper envenomation. In this study, the nefrotoxicity of a main component of B. leucurus venom called L-aminoacid oxidase (LAAO-Bl) was evaluated by using tubular epithelial cell lines MDCK and HK-2 and perfused kidney from rats. LAAO-Bl exhibited cytotoxicity, inducing apoptosis and necrosis in MDCK and HK-2 cell lines in a concentration-dependent manner. MDCK apoptosis induction was accompanied by Ca2+ release from the endoplasmic reticulum, reactive oxygen species (ROS) generation and mitochondrial dysfunction with enhanced expression of Bax protein levels. LAAO-Bl induced caspase-3 and caspase-7 activation in both cell lines. LAAO-Bl (10 μg/mL) exerts significant effects on the isolated kidney perfusion increasing perfusion pressure and urinary flow and decreasing the glomerular filtration rate and sodium, potassium and chloride tubular transport. Taken together our results suggest that LAAO-Bl is responsible for the nephrotoxicity observed in the envenomation by snakebites. Moreover, the cytotoxic of LAAO-Bl to renal epithelial cells might be responsible, at least in part, for the nephrotoxicity observed in isolated kidney. PMID:26193352

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

    PubMed

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

    2016-01-01

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

  18. Ketoconazole attenuates radiation-induction of tumor necrosis factor

    SciTech Connect

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

    1994-07-01

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

  19. Acute renal failure due to phenazopyridine (Pyridium) overdose: case report and review of the literature.

    PubMed

    Onder, Ali Mirza; Espinoza, Veronica; Berho, Mariana E; Chandar, Jayanthi; Zilleruelo, Gaston; Abitbol, Carolyn

    2006-11-01

    Phenazopyridine (Pyridium) is a commonly used urinary tract analgesic. It has been associated with yellow skin discoloration, hemolytic anemia, methemoglobinemia, and acute renal failure, especially in patients with preexisting kidney disease. We report a 17-year-old female with vertically transmitted human immunodeficiency virus (HIV) infection, presenting with acute renal failure and methemoglobinemia following a suicidal attempt with a single 1,200 mg ingestion of Pyridium. She had no prior evidence of HIV nephropathy. The patient had a progressive nonoliguric renal failure on the 3rd day following the ingestion. She was treated with N-acetylcysteine, intravenous carnitine, and alkalinization of the urine. Her kidney biopsy revealed acute tubular necrosis with no glomerular changes. After 7 days of conservative management, she was discharged home with normal kidney function. To our knowledge, this is the second smallest amount of Pyridium overdose resulting in acute renal failure with no previous history of kidney disease. PMID:16897003

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. Draft genome sequence of pathogenic bacteria Vibrio parahaemolyticus strain Ba94C2, associated with acute hepatopancreatic necrosis disease isolate from South America.

    PubMed

    Restrepo, Leda; Bayot, Bonny; Betancourt, Irma; Pinzón, Andres

    2016-09-01

    Vibrio parahaemolyticus is a pathogenic bacteria which has been associated to the early mortality syndrome (EMS) also known as hepatopancreatic necrosis disease (AHPND) causing high mortality in shrimp farms. Pathogenic strains contain two homologous genes related to insecticidal toxin genes, PirA and PirB, these toxin genes are located on a plasmid contained within the bacteria. Genomic sequences have allowed the finding of two strains with a divergent structure related to the geographic region from where they were found. The isolates from the geographic collection of Southeast Asia and Mexico show variable regions on the plasmid genome, indicating that even though they are not alike they still conserve the toxin genes. In this paper, we report for the first time, a pathogenic V. parahaemolyticus strain in shrimp from South America that showed symptoms of AHPND. The genomic analysis revealed that this strain of V. parahaemolyticus found in South America appears to be more related to the Southeast Asia as compared to the Mexican strains. This finding is of major importance for the shrimp industry, especially in regards to the urgent need for disease control strategies to avoid large EMS outbreaks and economic loss, and to determine its dispersion in South America. The whole-genome shotgun project of V. parahaemolyticus strain Ba94C2 have been deposited at DDBJ/EMBL/GenBank under the accession PRJNA335761. PMID:27570736

  3. Expandable tubulars for use in geologic structures

    DOEpatents

    Spray, Jeffery A.; Svedeman, Steven; Walter, David; Mckeighan, Peter; Siebanaler, Shane; Dewhurst, Peter; Hobson, Steven; Foss, Doug; Wirz, Holger; Sharpe, Aaron; Apostal, Michael

    2014-08-12

    An expandable tubular includes a plurality of leaves formed from sheet material that have curved surfaces. The leaves extend around a portion or fully around the diameter of the tubular structure. Some of the adjacent leaves of the tubular are coupled together. The tubular is compressed to a smaller diameter so that it can be inserted through previously deployed tubular assemblies. Once the tubular is properly positioned, it is deployed and coupled or not coupled to a previously deployed tubular assembly. The tubular is useful for all types of wells and boreholes.

  4. Tapered, tubular polyester fabric

    NASA Technical Reports Server (NTRS)

    Lapointe, Donat J. E. (Inventor); Wright, Lawrence T. (Inventor); Vincent, Laurence J. (Inventor)

    1987-01-01

    A tapered tubular polyester sleeve is described to serve as the flexible foundation for a spacesuit limb covering. The tube has a large end and a small end with a length to be determined. The ratio of taper is also determined by scale factors. All the warp yarns extend to the large end. A requisite number of warp yarns extend the full length of the sleeve. Other warp yarns extend from the large end but are terminated along the length of the sleeve. It is then woven with a filling yarn which extends in a full circle along the full length of the sleeve to thereby define the tapered sleeve. The sleeve after fabrication is then placed on a mandrel, heated in an oven, and then attached to the arm or other limb of the spacesuit.

  5. Tapered, tubular polyester fabric

    NASA Technical Reports Server (NTRS)

    LaPointe, Donat J. E. (Inventor); Vincent, Laurence J. (Inventor); Wright, Lawrence T. (Inventor)

    1988-01-01

    A tapered tubular polyester sleeve as set forth. It has a large end 12 and a small end 14 with a length to be determined. The ratio of taper is also determined by scale factors. All the warp yarns extend to the large end 12. A requisite number of warp yarns 16 extend the full length of the sleeve. Other warp yarns exemplified at 18, 22, 26, 28, 30 and 32 extend from the large end but are terminated along the length of the sleeve. It is then woven with a filling yarn 40 which extends in a full circle along the full length of the sleeve to thereby define the tapered sleeve. The sleeve after fabrication is then placed on a mandrel 42, heated in an oven 44 and is thereafter placed on the arm or other limb of a space suit exemplified at 50.

  6. Immobilized tubular fermentor

    SciTech Connect

    Gencer, M.A.; Mutharasan, R.

    1983-09-01

    In this article, a mathematical model describing the kinetics of ethanol fermentation in a whole cell immobilized tubular fermentor is proposed. Experimental results show reasonable agreement with the proposed model. A procedure for treating the fermentation data for determining the ethanol inhibition constants k1 and k2 is described. The ethanol productivity of the immobilized cell fermentor is compared with those of traditional fermentors. Experimental studies indicate that with Saccharomyces cerevisiae (NRRL Y132) culture, ethanol productivity in the range 21.2-83.7 g ethanol/L/h at ethanol concentration of 76-60 g/L can be achieved. This is comparable to or higher than those reported in the literature for yeast. The product yield factor of 0.5 g ethanol/g glucose was obtained. The immobilized cell fermentor does not show washout at dilution rates of 7/h and shows good stability over a 650-h operating period.

  7. Hyperbaric Oxygen Therapy Suppresses Apoptosis and Promotes Renal Tubular Regeneration After Renal Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Migita, Heihachi; Yoshitake, Shigenori; Tange, Yoshihiro; Choijookhuu, Narantsog; Hishikawa, Yoshitaka

    2016-01-01

    Background: Renal ischemia/reperfusion (I/R) injury remains a major cause of acute kidney injury (AKI), in addition to I/R injury-induced tissue inflammation, necrosis and apoptosis. Hyperbaric oxygen therapy (HBO) is defined as a treatment in which a patient is intermittently exposed to 100% oxygen pressurized to a pressure above sea level (> 2.0 atmospheres absolute (ATA), 1.0 ATA = 760 mmHg). It has been used in a number of medical conditions with a proven efficacy in a limited number of disorders. However, the effects of HBO therapy on apoptosis and proliferative activity after I/R injury have not been fully understood. Objectives: We studied the possible beneficial effects of HBO therapy on apoptosis and tubular cell regeneration after renal I/R injury in rats. Materials and Methods: Sprague-Dawley (SD) rats were randomized into three groups: Sham (Sham-operated rats); I/R (animals submitted to I/R); and I/R + HBO (I/R rats exposed to HBO). Tubular cell apoptosis was confirmed by DNA laddering and the terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL) assay. Cellular proliferation activity was determined using the anti-Ki-67 antibody. Results: A significant decrease in apoptotic cells and increase in proliferative reaction were observed in the I/R + HBO group compared to the I/R group. Conclusions: We demonstrated that HBO suppressed apoptosis, which caused inflammation after renal I/R, and promoted tubular cell regeneration. HBO has protective effects against AKI caused by renal I/R through the inhibition of apoptosis. PMID:26981502

  8. Tumour necrosis factor soluble receptors behave as acute phase reactants following surgery in patients with rheumatoid arthritis, chronic osteomyelitis and osteoarthritis.

    PubMed Central

    Chikanza, I C; Roux-Lombard, P; Dayer, J M; Panayi, G S

    1993-01-01

    Tumour necrosis factor-alpha (TNF-alpha) is involved in diverse biological processes including immune and inflammatory reactions and the response to surgical stress. Two soluble TNF receptor protein fragments, TNF-sR55 (from the p55 kD TNF receptor) and TNF-sR75 (from the p75 kD TNF receptor), are released by cells during inflammation and may modulate the e effects of TNF-alpha. We have studied the kinetics of secretion of TNF-alpha, TNF-sR55 and TNF-sR75 in the sera of patients with rheumatoid arthritis (RA) and control subjects with osteoarthritis (OA) or chronic osteomyelitis (OM) before and after major surgery. Significantly higher pre-operative levels of TNF-sR55 and TNF-sR75 were found in RA and OM as compared with OA (P < 0.02). Following surgery, TNF-sR55 increased within 24 h in RA, OM and OA (P < 0.05), whereas TNF-sR75 increased significantly only in OM and OA patients (P < 0.05). By contrast, no TNF-alpha was detectable before and after surgery in any of the subjects, but this may have been due to impaired detection (by ELISA) of TNF-alpha when it is bound to TNF-sR. These findings suggest that TNF-sR55 and TNF-sR75 may be further markers of the host's reaction to inflammatory insults. They may also play a role in modulating the immune and inflammatory reactions by inhibiting the systemic effects of TNF-alpha. PMID:8385584

  9. Effects of Schizolobium parahyba Extract on Experimental Bothrops Venom-Induced Acute Kidney Injury

    PubMed Central

    Martines, Monique Silva; Mendes, Mirian M.; Shimizu, Maria H. M.; Melo Rodrigues, Veridiana; de Castro, Isac; Filho, Sebastião R. Ferreira; Malheiros, Denise M. A. C.; Yu, Luis; Burdmann, Emmanuel A.

    2014-01-01

    Background Venom-induced acute kidney injury (AKI) is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP) extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV)-induced AKI. Methodology Groups of 8 to 10 rats received infusions of 0.9% saline (control, C), SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T) in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Doppler), blood pressure (BP, intra-arterial transducer), renal vascular resistance (RVR), urinary osmolality (UO, freezing point), urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA]), lactate dehydrogenase (LDH, kinetic method), hematocrit (Hct, microhematocrit), fibrinogen (Fi, Klauss modified) and blinded renal histology (acute tubular necrosis score). Principal Findings BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. Conclusion SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR. PMID:24551041

  10. Olfactory mucosal necrosis in rats following acute intraperitoneal administration of 1,2-diethylbenzene, 1,2-diacetylbenzene and 2,5-hexanedione.

    PubMed

    Gagnaire, François; Boucard, Stéphane

    2014-03-01

    1,2-Diethylbenzene (1,2-DEB) is used in the manufacture of some plastics. Exposure to 1,2-DEB has been shown to induce peripheral neuropathy in rats. This neurotoxicity is thought to be caused by a metabolite, 1,2-diacetylbenzene (1,2-DAB), a γ-diketone-like compound. 1,2-DEB was previously shown to be extensively and rapidly taken up by the nasal mucosa in male rats. In the present study, the nasal mucosa in rats exposed to 1,2-DEB and 1,2-DAB were examined histologically. Results were compared to sections from rats exposed to two other DEB isomers - 1,3-diethylbenzene (1,3-DEB) and 1,4-diethylbenzene (1,4-DEB) - and to two other neurotoxic compounds - n-hexane and its γ-diketone metabolite, 2,5-hexanedione (2,5-HD). A single intraperitoneal dose of 1,2-DEB (200mg/kg) induced time-dependent necrosis in the olfactory epithelium and Bowman's glands, with lesions appearing from the earliest observation time (4h) in the dorsomedial olfactory mucosa. Lesions spread through the lateral and ventral parts of the ethmoturbinates over the following days. The dorsal and medial zones of the nasal cavity started to regenerate from 72h after treatment, with the new epithelium showing metaplasia. One month after treatment, most of the olfactory epithelium had returned to normal. 1,2-DAB (40mg/kg) caused the same lesions as those observed after treatment with 1,2-DEB. Treatment with 2,5-HD (1g/kg) also caused lesions of the olfactory epithelium, mainly at level IV. However, these were comparatively less severe than those observed after exposure to 1,2-DEB. In contrast, intraperitoneal injection of 1,3-DEB (800mg/kg), 1,4-DEB (800mg/kg) and n-hexane (2g/kg) did not affect the nasal mucosa. Pretreatment of rats with 5-phenyl-1-pentyne, an inhibitor of CYP2F2 and CYP2E1 completely inhibited the olfactory toxicity caused by 1,2-DEB. These results suggest that metabolic activation of 1,2-DEB may be responsible for the toxicity observed. PMID:24373906

  11. Protective effect of nitric oxide in aristolochic acid-induced toxic acute kidney injury: an old friend with new assets.

    PubMed

    Declèves, Anne-Émilie; Jadot, Inès; Colombaro, Vanessa; Martin, Blanche; Voisin, Virginie; Nortier, Joëlle; Caron, Nathalie

    2016-01-01

    Aristolochic acid (AA) nephropathy (AAN), a progressive tubulointerstitial injury of toxic origin, is characterized by early and transient acute tubular necrosis. This process has been demonstrated to be associated with reduced nitric oxide (NO) production, which can disrupt the regulation of renal function. In this study, we tested the hypothesis that L-arginine (L-Arg) supplementation could restore renal function and reduce renal injury after AA intoxication. C57BL/6 J male mice were randomly subjected to daily i.p. injection of either sterile saline solution or AA (2.5 mg kg(-1)) for 4 days. To determine whether AA-induced renal injuries were linked to reduced NO production, L-Arg, a substrate for NO synthase, was supplemented (5%) in drinking water. Mice intoxicated with AA exhibited features of rapid-onset acute kidney injury, including polyuria, significantly increased plasma creatinine concentrations, proteinuria and fractional excretion of sodium (P < 0.05), along with severe proximal tubular cell injury and increased NADPH oxidase 2 (Nox2)-derived oxidative stress (P < 0.05). This was associated with a significant reduction in NO bioavailability. L-Arg supplementation in AA-treated mice significantly increased NO bioavailability, which in turn improved renal function (creatininaemia, polyuria, proteinuria, fractional excreted sodium and N-acetyl-β-D-glucosaminidase enzymuria) and renal structure (tubular necrosis and tubular cell apoptosis). These changes were associated with significant reductions in Nox2 expression and in production of reactive oxygen species and with an increase in antioxidant concentrations. Our results demonstrate that preservation of NO bioavailability leads to renal protection in AA-induced acute kidney injury by reducing oxidative stress and maintaining renal function. PMID:26442795

  12. Fat Necrosis and Oil Cysts

    MedlinePlus

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

  13. Device for inserting tubular members together

    SciTech Connect

    Milberger, L.J.

    1992-03-17

    This patent describes a well, a lower tubular member with a sealing surface located in the well, an upper tubular member which inserts into engagement with the lower tubular member during running in, the upper and lower tubular members being exposed to well fluid pressure, an improved means for sliding the upper tubular member into engagement with the lower tubular member. It comprises the upper tubular member having a first side and a second side, the second side having a sealing section which mates with the sealing surface of the lower tubular sidewall; axially spaced apart seal means located on the running tool sidewall for sealingly engaging the first side of the upper tubular member above and below the sealing section during running in, for defining a low pressure area between the running tool and the first side which is isolated from the well fluid pressure; the sealing section of the upper tubular member being exposed to well fluid pressure during running in, resulting in a pressure difference across the upper tubular member between the first side of the tubular member and the sealing section, means for eliminating the pressure difference across the upper tubular member between the first side and the sealing section after the upper tubular member has reached its engaged position with the lower tubular member, allowing the sealing section to move radially into engagement with the sealing surface. This patent also describes a method for sliding an upper tubular member into engagement with a sealing surface of a lower tubular member in a well having well fluid pressure, comprising in combination: providing the upper tubular member with a first side and a second side and providing the second side with a sealing section for mating with the sealing surface of the lower tubular member.

  14. Acute bile nephropathy secondary to anabolic steroids.

    PubMed

    Alkhunaizi, Ahmed M; ElTigani, Mohamed A; Rabah, Rola S; Nasr, Samih H

    2016-02-01

    Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis. PMID:26587777

  15. Renal papillary necrosis

    MedlinePlus

    ... renal papillary necrosis, especially after taking over-the-counter pain medicines ... diabetes or sickle cell anemia may reduce your risk. To prevent renal ... over-the-counter pain relievers. Do not take more than the ...

  16. Cortical laminar necrosis following myocardial infarction.

    PubMed

    Lattanzi, Simona; Silvestrini, Mauro; Provinciali, Leandro

    2016-01-01

    The cortical laminar necrosis (CLN) is a permanent injury characterized by the selective delayed necrosis of the cerebral cortex, mainly of the third layer, and usually greater in the depths and sides of the sulci than over the crest of the gyri. The damage involves all cellular components - either neurons, glia cells and blood vessels - and results in a focal cortical band of pan-necrosis detectable in late sub-acute or chronic stages of reduced energy supply to the brain. The CLN has been described in different conditions as hypoxia, hypoglycemia and status epilepticus. At brain CT or MR scans it appears with pathognomonic highly hyperdense or T1-hyperintense lesions following the gyral anatomy of the cerebral cortex. We reported a case of CLN associated to myocardial infarct and discussed the underlying mechanisms. PMID:27375142

  17. Hypokalemic quadriparesis and rhabdomyolysis as a rare presentation of distal renal tubular acidosis.

    PubMed

    Ahmad Bhat, Manzoor; Ahmad Laway, Bashir; Mustafa, Farhat; Shafi Kuchay, Mohammad; Mubarik, Idrees; Ahmad Palla, Nazir

    2014-01-01

    Distal renal tubular acidosis is a syndrome of abnormal urine acidification and is characterized by hyperchloremic metabolic acidosis, hypokalemia, hypercalciurea, nephrocalcinosis and nephrolithiasis. Despite the presence of persistent hypokalemia, acute muscular paralysis is rarely encountered in males. Here, we will report an eighteen year old male patient who presented with flaccid quadriparesis and was subsequently found to have rhabdomyolysis, severe short stature, skeletal deformities and primary distal renal tubular acidosis. PMID:25250276

  18. Urine Microscopy Is Associated with Severity and Worsening of Acute Kidney Injury in Hospitalized Patients

    PubMed Central

    Coca, Steven G.; Hall, Isaac E.; Iyanam, Umo; Koraishy, Madiha; Parikh, Chirag R.

    2010-01-01

    Background and objectives: Serum creatinine concentration at the time of nephrology consultation is not necessarily indicative of the severity of acute kidney injury (AKI). Although urine microscopy is useful to differentiate AKI, its role in predicting adverse clinical outcomes has not been well described. Design, setting, participants, & measurements: The relationship between urine microscopy findings at the time of nephrology consultation for AKI and clinical outcomes was evaluated prospectively. A urinary sediment scoring system was created on the basis of the number of renal tubular epithelial cells and granular casts. The primary outcome was worsening of AKI (progressing to higher AKI Network stage, dialysis, or death) during hospitalization. Results: Of 249 patients consulted for AKI, 197 had acute tubular necrosis or prerenal AKI and were included in the analysis. At consultation, 80 (40%) had stage 1, 53 (27%) had stage 2, and 66 (33%) had stage 3 AKI. The urinary sediment combined scores were lowest in those with stage 1 and highest in stage 3 AKI. Seventy-nine patients (40%) experienced worsening of AKI from the time of consultation. The urinary scoring system was significantly associated with increased risk of worsening AKI (adjusted relative risk: 7.3; 95% confidence interval: 4.5 to 9.7 for worsening with score of ≥3 versus score of 0) and was more predictive than AKI Network stage at the time of consultation. Conclusions: The urinary sediment score may be a useful tool to predict worsening of AKI due to either acute tubular necrosis or prerenal AKI during hospitalization. PMID:20089493

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

    PubMed

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

    2015-11-01

    Processes of apoptosis and necrosis of peripheral neutrophils were investigated in 43 patients, operated on for an acute abdominal organs diseases on the first and fourth postoperative days. Changes of apoptosis and necrosis processes in peripheral neutrophils in dynamics were established. Unfavorable course of early postoperative period in patients with initial high and average risk of postoperative peritonitis occurrence was accompanied by shift in necrosis/apoptosis ratio towards necrosis of peripheral neutrophils. PMID:26939426

  20. Acute kidney injury and hyperbilirubinemia in a young male after ingestion of Tribulus terrestris.

    PubMed

    Ryan, Margaret; Lazar, Ira; Nadasdy, Gyongyi M; Nadasdy, Tibor; Satoskar, Anjali A

    2015-03-01

    Acute tubular necrosis (ATN), especially from toxic injury is frequently accompanied by tubular casts and crystals. Myeloma casts, myoglobin, red blood cell and granular casts are well described. However, bile casts in tubules are rarely seen. We describe a case of Tribulus terrestris toxicity in a young healthy male, presenting with severe hyperbilirubinemia followed by acute renal failure and bile containing casts in the tubules. Tribulus terrestris is an herb often used by athletes as a nutritional supplement for performance enhancement. Although it is thought to be relatively safe, serious side effects have been reported before. Our aim is to increase awareness of the potential toxicities of performance enhancing herbal medications. These are often sold over-the-counter and therefore casually used, especially by young healthy individuals. Beneficial effects are controversial. Under-reporting by patients and infrequent documentation by health-care providers can delay diagnosis. We elaborately describe the kidney biopsy findings in Tribulus terrestris toxicity, and also provide a concise overview of the spectrum of tubular casts and their staining patterns, found in various kidney diseases. PMID:25295577

  1. Potential Reparative Role of Resident Adult Renal Stem/Progenitor Cells in Acute Kidney Injury

    PubMed Central

    Sallustio, Fabio; Serino, Grazia; Schena, Francesco Paolo

    2015-01-01

    Abstract Human kidney is particularly susceptible to ischemia and toxins with consequential tubular necrosis and activation of inflammatory processes. This process can lead to the acute renal injury, and even if the kidney has a great capacity for regeneration after tubular damage, in several circumstances, the normal renal repair program may not be sufficient to achieve a successful regeneration. Resident adult renal stem/progenitor cells could participate in this repair process and have the potentiality to enhance the renal regenerative mechanism. This could be achieved both directly, by means of their capacity to differentiate and integrate into the renal tissues, and by means of paracrine factors able to induce or improve the renal repair or regeneration. Recent genetic fate-tracing studies indicated that tubular damage is instead repaired by proliferative duplication of epithelial cells, acquiring a transient progenitor phenotype and by fate-restricted clonal cell progeny emerging from different nephron segments. In this review, we discuss about the properties and the reparative characteristics of high regenerative CD133+/CD24+ cells, with a view to a future application of these cells for the treatment of acute renal injury. PMID:26309808

  2. Downregulation of renal tubular Wnt/β-catenin signaling by Dickkopf-3 induces tubular cell death in proteinuric nephropathy

    PubMed Central

    Wong, D W L; Yiu, W H; Wu, H J; Li, R X; Liu, Y; Chan, K W; Leung, J C K; Chan, L Y Y; Lai, K N; Tang, S C W

    2016-01-01

    Studies on the role of Wnt/β-catenin signaling in different forms of kidney disease have yielded discrepant results. Here, we report the biphasic change of renal β-catenin expression in mice with overload proteinuria in which β-catenin was upregulated at the early stage (4 weeks after disease induction) but abrogated at the late phase (8 weeks). Acute albuminuria was observed at 1 week after bovine serum albumin injection, followed by partial remission at 4 weeks that coincided with overexpression of renal tubular β-catenin. Interestingly, a rebound in albuminuria at 8 weeks was accompanied by downregulated tubular β-catenin expression and heightened tubular apoptosis. In addition, there was an inverse relationship between Dickkopf-3 (Dkk-3) and renal tubular β-catenin expression at these time points. In vitro, a similar trend in β-catenin expression was observed in human kidney-2 (HK-2) cells with acute (upregulation) and prolonged (downregulation) exposure to albumin. Induction of a proapoptotic phenotype by albumin was significantly enhanced by silencing β-catenin in HK-2 cells. Finally, Dkk-3 expression and secretion was increased after prolonged exposure to albumin, leading to the suppression of intracellular β-catenin signaling pathway. The effect of Dkk-3 on β-catenin signaling was confirmed by incubation with exogenous Dkk-3 in HK-2 cells. Taken together, these data suggest that downregulation of tubular β-catenin signaling induced by Dkk-3 has a detrimental role in chronic proteinuria, partially through the increase in apoptosis. PMID:27010856

  3. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of urinary protein in acute kidney injury.

    PubMed

    Suhail, Sufi M; Woo, K T; Tan, H K; Wong, K S

    2011-07-01

    Recent experimental and clinical studies have shown the importance of urinary proteomics in acute kidney injury (AKI). We analyzed the protein in urine of patients with clinical AKI using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) for its diagnostic value, and followed them up for 40 months to evaluate prognosis. Urine from 31 consecutive cases of AKI was analyzed with SDS-PAGE to determine the low, middle and high molecular weight proteins. Fractional excretion of sodium (FENa) was estimated from serum and urine creatinine and sodium (Na). The cases were followed-up for 40 months from the end of the recruitment of study cases. Glomerular protein was higher in the hematuria group when compared with the non-hematuria group (P <0.04) and in the AKI group than in the acute on chronic renal failure (AKI-on-CRF) group (P <0.002). Tubular protein was higher in the AKI-on-CRF group (P <0.003) than in the AKI group. Tubular protein correlated with FENa in groups with diabetes mellitus (DM), AKI-on-CRF, and without hematuria (P <0.03, P <0.02 and P <0.004, respectively). Pattern of protein did not differ between groups with and without DM and clinical acute tubular necrosis (ATN). At the end of 40 months follow-up, category with predominantly glomerular protein progressed to chronic renal failure (CRF) or end-stage renal failure in higher proportion (P <0.05). In clinical AKI, we observed that glomerular protein dominated in cases with glomerular insult, as indicated by hematuria. Tubular protein was common in the study cases with CRF, DM and cases without hematuria. This indicates tubulo-interstitial injury for AKI in these cases. Patients with predominantly glomerular protein had an adverse outcome. PMID:21743220

  4. Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

    PubMed

    Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

    2016-01-01

    The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. PMID:26319781

  5. Hemodynamic and Tubular Changes Induced by Contrast Media

    PubMed Central

    Caiazza, Antonella; Russo, Luigi; Russo, Domenico

    2014-01-01

    The incidence of acute kidney injury induced by contrast media (CI-AKI) is the third cause of AKI in hospitalized patients. Contrast media cause relevant alterations both in renal hemodynamics and in renal tubular cell function that lead to CI-AKI. The vasoconstriction of intrarenal vasculature is the main hemodynamic change induced by contrast media; the vasoconstriction is accompanied by a cascade of events leading to ischemia and reduction of glomerular filtration rate. Cytotoxicity of contrast media causes apoptosis of tubular cells with consequent formation of casts and worsening of ischemia. There is an interplay between the negative effects of contrast media on renal hemodynamics and on tubular cell function that leads to activation of renin-angiotensin system and increased production of reactive oxygen species (ROS) within the kidney. Production of ROS intensifies cellular hypoxia through endothelial dysfunction and alteration of mechanisms regulating tubular cells transport. The physiochemical characteristics of contrast media play a critical role in the incidence of CI-AKI. Guidelines suggest the use of either isoosmolar or low-osmolar contrast media rather than high-osmolar contrast media particularly in patients at increased risk of CI-AKI. Older age, presence of atherosclerosis, congestive heart failure, chronic renal disease, nephrotoxic drugs, and diuretics may multiply the risk of CI-AKI. PMID:24678510

  6. Hemodynamic and tubular changes induced by contrast media.

    PubMed

    Caiazza, Antonella; Russo, Luigi; Sabbatini, Massimo; Russo, Domenico

    2014-01-01

    The incidence of acute kidney injury induced by contrast media (CI-AKI) is the third cause of AKI in hospitalized patients. Contrast media cause relevant alterations both in renal hemodynamics and in renal tubular cell function that lead to CI-AKI. The vasoconstriction of intrarenal vasculature is the main hemodynamic change induced by contrast media; the vasoconstriction is accompanied by a cascade of events leading to ischemia and reduction of glomerular filtration rate. Cytotoxicity of contrast media causes apoptosis of tubular cells with consequent formation of casts and worsening of ischemia. There is an interplay between the negative effects of contrast media on renal hemodynamics and on tubular cell function that leads to activation of renin-angiotensin system and increased production of reactive oxygen species (ROS) within the kidney. Production of ROS intensifies cellular hypoxia through endothelial dysfunction and alteration of mechanisms regulating tubular cells transport. The physiochemical characteristics of contrast media play a critical role in the incidence of CI-AKI. Guidelines suggest the use of either isoosmolar or low-osmolar contrast media rather than high-osmolar contrast media particularly in patients at increased risk of CI-AKI. Older age, presence of atherosclerosis, congestive heart failure, chronic renal disease, nephrotoxic drugs, and diuretics may multiply the risk of CI-AKI. PMID:24678510

  7. A Simple Tubular Reactor Experiment.

    ERIC Educational Resources Information Center

    Hudgins, Robert R.; Cayrol, Bertrand

    1981-01-01

    Using the hydrolysis of crystal violet dye by sodium hydroxide as an example, the theory, apparatus, and procedure for a laboratory demonstration of tubular reactor behavior are described. The reaction presented can occur at room temperature and features a color change to reinforce measured results. (WB)

  8. Pathophysiology of cisplatin-induced acute kidney injury.

    PubMed

    Ozkok, Abdullah; Edelstein, Charles L

    2014-01-01

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

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

    PubMed

    Nassour, Ibrahim; Ramzan, Zeeshan; Kukreja, Sachin

    2016-09-01

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

  10. Bidirectional signalling between EphA2 and ephrinA1 increases tubular cell attachment, laminin secretion and modulates erythropoietin expression after renal hypoxic injury.

    PubMed

    Rodriguez, Stéphane; Rudloff, Stefan; Koenig, Katrin Franziska; Karthik, Swapna; Hoogewijs, David; Huynh-Do, Uyen

    2016-08-01

    Acute kidney injury (AKI) is common in hospitalized patients and has a poor prognosis, the severity of AKI being linked to progression to chronic kidney disease. This stresses the need to search for protective mechanisms during the acute phase. We investigated kidney repair after hypoxic injury using a rat model of renal artery branch ligation, which led to an oxygen gradient vertical to the corticomedullary axis. Three distinct zones were observed: tubular necrosis, infarction border zone and preserved normal tissue. EphA2 is a receptor tyrosine kinase with pivotal roles in cell architecture, migration and survival, upon juxtacrine contact with its membrane-bound ligand EphrinA1. Following hypoxia, EphA2 was up-regulated in cortical and medullary tubular cells, while EphrinA1 was up-regulated in interstitial cells adjacent to peritubular capillaries. Moreover, erythropoietin (EPO) messenger RNA (mRNA) was strongly expressed in the border zone of infarcted kidney within the first 6 h. To gain more insight into the biological impact of EphA2 and EphrinA1 up-regulation, we activated the signalling pathways in vitro using recombinant EphrinA1/Fc or EphA2/Fc proteins. Stimulation of EphA2 forward signalling in the proximal tubular cell line HK2 increased cell attachment and laminin secretion at the baso-lateral side. Conversely, activation of reverse signalling through EphrinA1 expressed by Hep3B cells promoted EPO production at both the transcriptional and protein level. Strikingly, in co-culture experiments, juxtacrine contact between EphA2 expressing MDCK and EphrinA1 expressing Hep3B was sufficient to induce a significant up-regulation of EPO mRNA production in the latter cells, even in the absence of hypoxic conditions. The synergistic effects of EphA2 and hypoxia led to a 15-20-fold increase of EPO expression. Collectively, our results suggest an important role of EphA2/EphrinA1 signalling in kidney repair after hypoxic injury through stimulation of (i) tubular

  11. Subcutaneous encapsulated fat necrosis.

    PubMed

    Aydin, Dogu; Berg, Jais O

    2016-04-01

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

  12. Micro-Tubular Fuel Cells

    NASA Technical Reports Server (NTRS)

    Kimble, Michael C.; Anderson, Everett B.; Jayne, Karen D.; Woodman, Alan S.

    2004-01-01

    Micro-tubular fuel cells that would operate at power levels on the order of hundreds of watts or less are under development as alternatives to batteries in numerous products - portable power tools, cellular telephones, laptop computers, portable television receivers, and small robotic vehicles, to name a few examples. Micro-tubular fuel cells exploit advances in the art of proton-exchange-membrane fuel cells. The main advantage of the micro-tubular fuel cells over the plate-and-frame fuel cells would be higher power densities: Whereas the mass and volume power densities of low-pressure hydrogen-and-oxygen-fuel plate-and-frame fuel cells designed to operate in the targeted power range are typically less than 0.1 W/g and 0.1 kW/L, micro-tubular fuel cells are expected to reach power densities much greater than 1 W/g and 1 kW/L. Because of their higher power densities, micro-tubular fuel cells would be better for powering portable equipment, and would be better suited to applications in which there are requirements for modularity to simplify maintenance or to facilitate scaling to higher power levels. The development of PEMFCs has conventionally focused on producing large stacks of cells that operate at typical power levels >5 kW. The usual approach taken to developing lower-power PEMFCs for applications like those listed above has been to simply shrink the basic plate-and-frame configuration to smaller dimensions. A conventional plate-and-frame fuel cell contains a membrane/electrode assembly in the form of a flat membrane with electrodes of the same active area bonded to both faces. In order to provide reactants to both electrodes, bipolar plates that contain flow passages are placed on both electrodes. The mass and volume overhead of the bipolar plates amounts to about 75 percent of the total mass and volume of a fuel-cell stack. Removing these bipolar plates in the micro-tubular fuel cell significantly increases the power density.

  13. Pancreatography after recovery from massive pancreatic necrosis.

    PubMed

    Howard, J M; Wagner, S M

    1989-01-01

    Massive retroperitoneal necrosis may follow life-threatening acute pancreatitis. At delayed operation, the surgeon may not be able to delineate dead pancreas from dead adipose tissue. The question arises: has "gloved hand" debridement resulted in pancreatectomy? The histologists report only "necrotic debris, of uncertain origin." To obtain objective data, pancreatography was performed in 13 patients, 10 weeks to 23 months after onset of massive pancreatic necrosis. Each patient had required delayed laparotomy for debridement and external drainage at some earlier stage of their illness. Pancreatography was correlated with the clinical assessment of diabetes and steatorrhea. Except in specific cases involving internal fistulae, pancreatography has not been previously reported in such patients. The results demonstrate that the main pancreatic duct usually maintained its normal length and configuration. Necrosis or stricture of the main duct, if it occurred, was more likely to be followed by diabetes. Steatorrhea was clinically detected in a single patient only. The necrotic tissue, up to several kilograms in wet weight, is largely dead adipose tissue. The pancreas, especially its head, is resistant to necrosis, much more resistant than is the retroperitoneal fat. PMID:2910213

  14. Synchronized renal tubular cell death involves ferroptosis

    PubMed Central

    Skouta, Rachid; Himmerkus, Nina; Mulay, Shrikant R.; Dewitz, Christin; De Zen, Federica; Prokai, Agnes; Zuchtriegel, Gabriele; Krombach, Fritz; Welz, Patrick-Simon; Weinlich, Ricardo; Vanden Berghe, Tom; Vandenabeele, Peter; Pasparakis, Manolis; Bleich, Markus; Weinberg, Joel M.; Reichel, Christoph A.; Bräsen, Jan Hinrich; Kunzendorf, Ulrich; Anders, Hans-Joachim; Stockwell, Brent R.; Green, Douglas R.; Krautwald, Stefan

    2014-01-01

    Receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is thought to be the pathophysiologically predominant pathway that leads to regulated necrosis of parenchymal cells in ischemia–reperfusion injury (IRI), and loss of either Fas-associated protein with death domain (FADD) or caspase-8 is known to sensitize tissues to undergo spontaneous necroptosis. Here, we demonstrate that renal tubules do not undergo sensitization to necroptosis upon genetic ablation of either FADD or caspase-8 and that the RIPK1 inhibitor necrostatin-1 (Nec-1) does not protect freshly isolated tubules from hypoxic injury. In contrast, iron-dependent ferroptosis directly causes synchronized necrosis of renal tubules, as demonstrated by intravital microscopy in models of IRI and oxalate crystal-induced acute kidney injury. To suppress ferroptosis in vivo, we generated a novel third-generation ferrostatin (termed 16-86), which we demonstrate to be more stable, to metabolism and plasma, and more potent, compared with the first-in-class compound ferrostatin-1 (Fer-1). Even in conditions with extraordinarily severe IRI, 16-86 exerts strong protection to an extent which has not previously allowed survival in any murine setting. In addition, 16-86 further potentiates the strong protective effect on IRI mediated by combination therapy with necrostatins and compounds that inhibit mitochondrial permeability transition. Renal tubules thus represent a tissue that is not sensitized to necroptosis by loss of FADD or caspase-8. Finally, ferroptosis mediates postischemic and toxic renal necrosis, which may be therapeutically targeted by ferrostatins and by combination therapy. PMID:25385600

  15. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    SciTech Connect

    Jiang, Zhenzhou Bao, Qingli Sun, Lixin Huang, Xin Wang, Tao Zhang, Shuang Li, Han Zhang, Luyong

    2013-01-15

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  16. Clinical & pathological features of acute toxicity due to Cassia occidentalis in vertebrates.

    PubMed

    Vashishtha, V M; John, T J; Kumar, Amod

    2009-07-01

    Cassia occidentalis is an annual shrub found in many countries including India. Although bovines and ovines do not eat it, parts of the plant are used in some traditional herbal medicines. Several animal studies have documented that fresh or dried beans are toxic. Ingestion of large amounts by grazing animals has caused serious illness and death. The toxic effects in large animals, rodents and chicken are on skeletal muscles, liver, kidney and heart. The predominant systems involved depend upon the animal species and the dose of the beans consumed. Brain functions are often affected. Gross lesions at necropsy consist of necrosis of skeletal muscle fibres and hepatic centrilobular necrosis; renal tubular necrosis is less frequent. Muscle and liver cell necrosis is reflected in biochemical abnormalities. The median lethal dose (LD(50)) is 1 g/kg for mice and rats. Toxicity is attributed to various anthraquinones and their derivatives and alkaloids, but the specific toxins have not been identified. Data on human toxicity are extremely scarce. This review summarizes information available on Cassia toxicity in animals and compares it with toxic features reported in children. The clinical spectrum and histopathology of C. occidentalis poisoning in children resemble those of animal toxicity, affecting mainly hepatic, skeletal muscle and brain tissues. The case-fatality rate in acute severe poisoning is 75-80 per cent in children. PMID:19700797

  17. Diagnostic features in 10 naturally occurring cases of acute fatal canine leptospirosis.

    PubMed

    Rissi, Daniel R; Brown, Cathy A

    2014-11-01

    The current report describes the diagnostic features in 10 cases of acute fatal canine leptospirosis with minimal renal and hepatic changes that may present a diagnostic challenge for the pathologist. Most affected dogs were less than 6 months of age and had a biochemical profile consistent with hepatorenal dysfunction. Clinical signs consisted of vomiting, depression, icterus, dehydration, diarrhea, and anorexia. All dogs died or were humanely euthanized within 3-7 days after the onset of clinical disease. Necropsy findings included pulmonary edema with hemorrhages, icterus, renal and hepatic pallor and swelling, and gastric edema with hemorrhage. Despite severe azotemia, histological changes in the kidneys were subtle in all dogs, and included mild renal tubular simplification, with single-cell necrosis and attenuation, along with minimal interstitial lymphoplasmacytic inflammation, edema, and hemorrhage. Hepatic lesions included scattered hepatocellular single-cell necrosis and hepatocellular dissociation. Prominent extrarenal lesions typically associated with uremia including vascular fibrinoid necrosis in multiple organs, pulmonary mineralization with occasional fibrinosuppurative exudation, and gastric mineralization were also present. Postmortem diagnostic confirmation was based on the detection of leptospiral antigen on fresh renal samples by fluorescent antibody test and on the demonstration of intact spirochetes in sections of kidneys using immunohistochemical staining. Acute fatal canine leptospirosis occurred as a fulminant hepatorenal disease affecting mainly young dogs, and the diagnosis was dependent on the recognition of the subtle renal changes with confirmation via fluorescent antibody testing or immunohistochemical staining. PMID:25274745

  18. [Acute kidney injury in children].

    PubMed

    Amira-Peco-Antić; Paripović, Dusan

    2014-01-01

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

  19. Renal tubular secretion of pramipexole.

    PubMed

    Knop, Jana; Hoier, Eva; Ebner, Thomas; Fromm, Martin F; Müller, Fabian

    2015-11-15

    The dopamine agonist pramipexole is cleared predominantly by the kidney with a major contribution of active renal secretion. Previously the organic cation transporter 2 (OCT2) was shown to be involved in the uptake of pramipexole by renal tubular cells, while the mechanism underlying efflux into tubular lumen remains unclear. Cimetidine, a potent inhibitor of multidrug and toxin extrusion proteins 1 (MATE1) and 2-K (MATE2-K), decreases renal pramipexole clearance in humans. We hypothesized that, in addition to OCT2, pramipexole may be a substrate of MATE-mediated transport. Pramipexole uptake was investigated using MDCK or HEK cells overexpressing OCT2, MATE1 or MATE2-K and the respective vector controls (Co). Transcellular pramipexole transport was investigated in MDCK cells single- or double-transfected with OCT2 and/or MATE1 and in Co cells, separating a basal from an apical compartment in a model for renal tubular secretion. Pramipexole uptake was 1.6-, 1.1-, or 1.6-folds in cells overexpressing OCT2, MATE1 or MATE2-K, respectively as compared to Co cells (p<0.05). In transcellular transport experiments, intracellular pramipexole accumulation was 1.7-folds in MDCK-OCT2 (p<0.001), and transcellular pramipexole transport was 2.2- and 4.0-folds in MDCK-MATE1 and MDCK-OCT2-MATE1 cells as compared to Co cells (p<0.001). Transcellular pramipexole transport was pH dependent and inhibited by cimetidine with IC50 values of 12μM and 5.5μM in MATE1 and OCT2-MATE1 cells, respectively. Taken together, coordinate activity of OCT2-mediated uptake and MATE-mediated efflux determines pramipexole renal secretion. Reduced OCT2 or MATE transport activity due to genetic variation or drug-drug interactions may affect pramipexole renal secretion. PMID:26360835

  20. Loss of α(E)-catenin promotes Fas mediated apoptosis in tubular epithelial cells

    PubMed Central

    Wang, Xinhui; Parrish, Alan R.

    2015-01-01

    The aging kidney undergoes structural and functional alterations which make it more susceptible to drug-induced acute kidney injury (AKI). Previous studies in our lab have shown that the expression of α(E)-catenin is decreased in aged kidney and loss of α(E)-catenin potentiates AKI-induced apoptosis, but not necrosis, in renal tubular epithelial cells (NRK-52E cells). However, the specific apoptotic pathway underlying the increased AKI-induced cell death is not yet understood. In this study, cells were challenged with nephrotoxicant cisplatin to induce AKI. A ~5.5-fold increase in Fas expression in C2 (stable α(E)-catenin knockdown) relative to NT3 (non-targeted control) cells was seen. Increased caspase-8 and -9 activation was induced by cisplatin in C2 as compared to NT3 cells. In addition, decreased Bcl-2 expression and increased BID cleavage and cytochrome C release were detected in C2 cells after cisplatin challenge. Treating the cells with cisplatin, in combination with a Bcl-2 inhibitor, decreased the viability of NT3 cells to the same level as C2 cells after cisplatin. Furthermore, caspase-3/-7 activation is blocked by Fas, caspase-8, caspase-9 and pan-caspase inhibitors. These inhibitors also completely abolished the difference in viability between NT3 and C2 cells in response to cisplatin. These results demonstrate a Fas-mediated apoptotic signaling pathway that is enhanced by the age-dependent loss of α(E)-catenin in renal tubule epithelial cells. PMID:25894537

  1. Ibuprofen-related renal tubular acidosis in pregnancy

    PubMed Central

    Mallett, Andrew; Lynch, Matthew; John, George T; Healy, Helen; Lust, Karin

    2011-01-01

    Ibuprofen-related renal tubular acidosis (RTA) has not been previously described in pregnancy but its occurrence outside of pregnancy is being increasingly described. In this case, a 34-year-old woman presented in the third trimester of pregnancy with Type 1 or distal RTA related to ibuprofen and codeine abuse. It was complicated by acute on chronic renal dysfunction and hypokalemia. Delivery at 37 weeks gestation due to concerns of evolving preeclampsia resulted in the birth of a healthy neonate. RTA and hypokalemia were remediated and ibuprofen and codeine abuse ceased. Some renal dysfunction however continued. Thorough and repeated history taking as well as vigilance for this condition is suggested.

  2. Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids

    PubMed Central

    Zhao, Aiyu; Tan, Maybel; Maung, Aung; Salifu, Moro; Mallappallil, Mary

    2015-01-01

    The use of synthetic cannabinoids (SCBs) is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI) requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs) in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73%) as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK) level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity. PMID:26550500

  3. Inorganic fluoride. Divergent effects on human proximal tubular cell viability.

    PubMed Central

    Zager, R. A.; Iwata, M.

    1997-01-01

    Fluoride (F) is a widely distributed nephrotoxin with exposure potentially resulting from environmental pollution and from fluorinated anesthetic use (eg, isoflurane). This study sought to characterize some of the subcellular determinants of fluoride cytotoxicity and to determine whether subtoxic F exposure affects tubular cell vulnerability to superimposed ATP depletion and nephrotoxic attack. Human proximal tubular cells (HK-2) were cultured with differing amounts of NaF (0 to 20 mmol/L, overlapping with clinically relevant intrarenal/urinary levels after fluorinated anesthetic use). After completing 24-hour exposures, cell injury was determined (vital dye uptake). Fluoride effects on cell deacylation ([3]H-C20:4 release) and PLA2 activity were also assessed. To determine whether subtoxic F exposure alters tubular cell susceptibility to superimposed injury, cells were exposed to subtoxic NaF doses for 0 to 24 hours and then challenged with simulated ischemia (ATP depletion plus Ca2+ overload) or a clinically relevant nephrotoxic insult (myoglobin exposure). NaF induced dose-dependent cytotoxicity (up to approximately 90% vital dye uptake and increased [3H]C20:4 release). Extracellular Ca2+ chelation (EGTA) and PLA2 inhibitor therapy (aristolochic acid, dibucaine, or mepacrine) each conferred significant protective effects. When subtoxic NaF doses were applied, partial cytosolic PLA2 depletion rapidly developed (approximately 85% within 3 hours, determined on cell extracts). These partially PLA2-depleted cells were markedly resistant to ATP depletion/Ca2+ ionophore injury and to myoglobin-induced attack (approximately 50% decrease in cell death). We conclude that 1) F induces dose-dependent cytotoxicity in cultured human proximal tubular cells, 2) this occurs, in part, via Ca(2+)- and PLA2-dependent mechanism(s), 3) partial cytosolic PLA2 depletion subsequently results, and 4) subtoxic fluoride exposure can acutely increase cell resistance to further attack

  4. Acute Kidney Injury in Patients with Cirrhosis

    PubMed Central

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

    2015-01-01

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

  5. Application of new acute kidney injury biomarkers in human randomized controlled trials.

    PubMed

    Parikh, Chirag R; Moledina, Dennis G; Coca, Steven G; Thiessen-Philbrook, Heather R; Garg, Amit X

    2016-06-01

    The use of novel biomarkers of acute kidney injury (AKI) in clinical trials may help evaluate treatments for AKI. Here we explore potential applications of biomarkers in simulated clinical trials of AKI using data from the TRIBE-AKI multicenter, prospective cohort study of patients undergoing cardiac surgery. First, in a hypothetical trial of an effective therapy at the time of acute tubular necrosis to prevent kidney injury progression, use of an indirect kidney injury marker such as creatinine compared to a new direct biomarker of kidney injury reduces the proportion of true acute tubular necrosis cases enrolled. The result is a lower observed relative risk reduction with the therapy, and lower statistical power to detect a therapy effect at a given sample size. Second, the addition of AKI biomarkers (interleukin-18 and NGAL) to clinical risk factors as eligibility criteria for trial enrollment in early AKI has the potential to increase the proportion of patients who will experience AKI progression and reduce trial cost. Third, we examine AKI biomarkers as outcome measures for the purposes of identifying therapies that warrant further testing in larger, multicenter, multi-country trials. In the hypothetical trial of lower cardiopulmonary bypass time to reduce the risk of postoperative AKI, the sample size required to detect a reduction in AKI is lower if new biomarkers are used to define AKI rather than serum creatinine. Thus, incorporation of new biomarkers of AKI has the potential to increase statistical power, decrease the sample size, and lower the cost of AKI trials. PMID:27165835

  6. Tubular inverse opal scaffolds for biomimetic vessels

    NASA Astrophysics Data System (ADS)

    Zhao, Ze; Wang, Jie; Lu, Jie; Yu, Yunru; Fu, Fanfan; Wang, Huan; Liu, Yuxiao; Zhao, Yuanjin; Gu, Zhongze

    2016-07-01

    There is a clinical need for tissue-engineered blood vessels that can be used to replace or bypass damaged arteries. The success of such grafts depends strongly on their ability to mimic native arteries; however, currently available artificial vessels are restricted by their complex processing, controversial integrity, or uncontrollable cell location and orientation. Here, we present new tubular scaffolds with specific surface microstructures for structural vessel mimicry. The tubular scaffolds are fabricated by rotationally expanding three-dimensional tubular inverse opals that are replicated from colloidal crystal templates in capillaries. Because of the ordered porous structure of the inverse opals, the expanded tubular scaffolds are imparted with circumferentially oriented elliptical pattern microstructures on their surfaces. It is demonstrated that these tailored tubular scaffolds can effectively make endothelial cells to form an integrated hollow tubular structure on their inner surface and induce smooth muscle cells to form a circumferential orientation on their outer surface. These features of our tubular scaffolds make them highly promising for the construction of biomimetic blood vessels.There is a clinical need for tissue-engineered blood vessels that can be used to replace or bypass damaged arteries. The success of such grafts depends strongly on their ability to mimic native arteries; however, currently available artificial vessels are restricted by their complex processing, controversial integrity, or uncontrollable cell location and orientation. Here, we present new tubular scaffolds with specific surface microstructures for structural vessel mimicry. The tubular scaffolds are fabricated by rotationally expanding three-dimensional tubular inverse opals that are replicated from colloidal crystal templates in capillaries. Because of the ordered porous structure of the inverse opals, the expanded tubular scaffolds are imparted with circumferentially

  7. Acquired distal renal tubular acidosis in man.

    PubMed

    Better, O S

    1982-10-01

    Distal renal tubular acidosis (dRTA) may complicate renal transplantation, liver cirrhosis, and obstructive uropathy. Indeed, its occurrence may be an early clue to an episode of rejection of the graft or to obstructive uropathy. The mechanism in most patients with dRTA is impaired distal secretion of protons. In some patients, however, back leak of protons from tubular lumen to blood may abolish distal tubular ability to maintain urine to blood proton gradients. In patients with obstructive uropathy the spectrum of tubular acidosis is widened by the occurrence of additional defects in tubular secretion of potassium and impairment of hydrogen ion secretion secondary to hypoaldosteronism. Hyperkalemia is also seen in "voltage dependent" states such as following the administration of lithium and amiloride. Hyperkalemia per se is conducive to acidosis by a combination of extrarenal and several intrarenal mechanisms. PMID:6755051

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

    PubMed Central

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

    2015-01-01

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

  9. Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging

    PubMed Central

    Jiang, Binghu; Wang, Jichen; Ni, Yicheng; Chen, Feng

    2013-01-01

    Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [123I]iodohypericin, [124I]iodohypericin, and [131I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin. PMID:24052807

  10. Mars Life? - Microscopic Tubular Structures

    NASA Technical Reports Server (NTRS)

    1996-01-01

    This electron microscope image shows tubular structures of likely Martian origin. These structures are very similar in size and shape to extremely tiny microfossils found in some Earth rocks. This photograph is part of a report by a NASA research team published in the Aug. 16, 1996, issue of the journal Science. A two-year investigation by the team found organic molecules, mineral features characteristic of biological activity and possible microscopic fossils such as these inside of an ancient Martian rock that fell to Earth as a meteorite. The largest possible fossils are less than 1/100th the diameter of a human hair in size while most are ten times smaller.

  11. Mars Life? - Microscopic Tubular Structures

    NASA Technical Reports Server (NTRS)

    1996-01-01

    This electron microscope image shows extremely tiny tubular structures that are possible microscopic fossils of bacteria-like organisms that may have lived on Mars more than 3.6 billion years ago. A two-year investigation by a NASA research team found organic molecules, mineral features characteristic of biological activity and possible microscopic fossils such as these inside of an ancient Martian rock that fell to Earth as a meteorite. The largest possible fossils are less than 1/100th the diameter of a human hair in size while most are ten times smaller. The fossil-like structures were found in carbonate minerals formed along pre-existing fractures in the meteorite in a fashion similar to the way fossils occur in limestone on Earth, although on a microscopic scale.

  12. Mechanisms of acute kidney injury induced by experimental Lonomia obliqua envenomation.

    PubMed

    Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R; Vieira, Maria Aparecida Ribeiro; Guimarães, Jorge Almeida

    2015-03-01

    Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. To characterize L. obliqua venom effects, we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery-based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman's space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increase the expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. In conclusion, the mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia's envenomation. PMID:24798088

  13. Mechanisms of Acute Kidney Injury Induced by Experimental Lonomia obliqua Envenomation

    PubMed Central

    Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O.; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R.; Ribeiro, Maria Aparecida; Guimarães, Jorge Almeida

    2015-01-01

    Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation. PMID:24798088

  14. Tubular inverse opal scaffolds for biomimetic vessels.

    PubMed

    Zhao, Ze; Wang, Jie; Lu, Jie; Yu, Yunru; Fu, Fanfan; Wang, Huan; Liu, Yuxiao; Zhao, Yuanjin; Gu, Zhongze

    2016-07-14

    There is a clinical need for tissue-engineered blood vessels that can be used to replace or bypass damaged arteries. The success of such grafts depends strongly on their ability to mimic native arteries; however, currently available artificial vessels are restricted by their complex processing, controversial integrity, or uncontrollable cell location and orientation. Here, we present new tubular scaffolds with specific surface microstructures for structural vessel mimicry. The tubular scaffolds are fabricated by rotationally expanding three-dimensional tubular inverse opals that are replicated from colloidal crystal templates in capillaries. Because of the ordered porous structure of the inverse opals, the expanded tubular scaffolds are imparted with circumferentially oriented elliptical pattern microstructures on their surfaces. It is demonstrated that these tailored tubular scaffolds can effectively make endothelial cells to form an integrated hollow tubular structure on their inner surface and induce smooth muscle cells to form a circumferential orientation on their outer surface. These features of our tubular scaffolds make them highly promising for the construction of biomimetic blood vessels. PMID:27241065

  15. Ileal bladder substitute: antireflux nipple or afferent tubular segment?

    PubMed

    Studer, U E; Spiegel, T; Casanova, G A; Springer, J; Gerber, E; Ackermann, D K; Gurtner, F; Zingg, E J

    1991-01-01

    Spheroidal bladder substitutes made from double-folded ileal segments, similar to Goodwin's cup-patch technique, are devoid of major coordinated wall contractions. This, together with the reservoir's direct anastomosis to the membranous urethra, prevents major intraluminal pressure peaks and assures a residue-free voiding of sterile urine. In order to determine whether, under these conditions, an afferent tubular isoperistaltic ileal segment of 20-cm length protects the upper urinary tract as efficiently as an antireflux nipple, 60 male patients who were subjected to radical cystectomy were prospectively randomised to groups in which a bladder substitute was formed together with either of these 2 antireflux devices. An analysis of the results obtained in 20 patients from each group who could be followed for more than 1 year (median observation time 30 and 36 months) showed no differences between the groups in metabolic disturbances, kidney size, reservoir capacity, diurnal and nocturnal urinary continence, the incidence of urinary tract infection or episodes of acute pyelonephritis. Later than 1 year postoperatively, intravenous urograms of the renoureteral units of 25% of the patients with antireflux nipples showed persistent but generally slight dilatation of the upper urinary tracts. This observation was significantly more frequent than it was in patients with afferent tubular segments. Urodynamic and radiographic studies showed that the competence of the antireflux nipples was secured by the raised surrounding intravesical pressure. This, however, also resulted in a transient functional obstruction, and a gradual rise of the basal pressure in the upper urinary tracts was recorded. In patients with afferent ileal tubular segments, contrast medium could be forced upwards into the renal pelvis when the bladder substitutes were overfilled. However, despite raised intravesical pressures, peristalsis in the isoperistaltic afferent tubular segment gradually returned

  16. Complete Penile Necrosis in a Patient With Heparin-induced Thrombocytopenia: A Case Report*

    PubMed Central

    Blais, Anne-Sophie; Deschênes Rompré, Marie-Pier; Lacombe, Louis

    2014-01-01

    Penile necrosis is a rare condition that has been mostly described in association with diabetes mellitus and end-stage renal disease. We report an unusual case of acute penile necrosis because of heparin-induced thrombocytopenia. A 75-year-old man presented with acute renal failure and experienced cardiac complications during the hospitalization. The patient was treated twice with intravenous heparin. He developed symptoms of penile necrosis 4 days after the reintroduction of heparin. At that moment, the platelet count dropped by 61%, and the analysis of heparin-pf4 antibodies was positive for heparin-induced thrombocytopenia. The patient underwent a total penectomy and a perineal urethrostomy. PMID:26954936

  17. Professor Eric G.L. Bywaters, Acute Kidney Injury and the "forgotten" letter.

    PubMed

    Almond, Michael

    2016-02-01

    The Bywaters seminal 1941 British Medical Journal paper on the crush syndrome was important both for its written content and for using a photomicrograph demonstrating pigmented casts in the renal tubules. He appeared to be reporting the first cases of renal failure secondary to crushing injuries. Most at this point would have been content yet Bywaters demonstrated both determination and humility by publishing a letter in the BMJ 4 months later. This letter, now almost forgotten and rarely referenced, significantly corrected his original paper. He identified that descriptions of the syndrome had been made before, not least by German pathologists in World War 1. The letter recognised various pathologists and surgeons, Colmers (1909) reporting on casualties from the Messina earthquake suffering from acute pressure necrosis and Frankenthal (1916) describing soldiers who had been buried in the trenches showing oedema, bloody urine and post mortem ischaemic muscle necrosis. Others were credited as describing similar cases in inaccessible journals or in "inaugural dissertations". Hackradt (1917) described injuries from burial with oedema of the leg and bloody urine containing albumin and casts, necropsy showed muscle necrosis and tubular degeneration in the kidneys with blood casts and Lewin (1919) described 3 similar cases. Bywaters subsequently credits Minami (1923) a Japanese dermatologist working in Germany for summarizing the literature and providing a description that tallied exactly with his own. Finally Bywaters puzzles why the standard textbooks on war surgery available in Great Britain and the U.S.A. in 1941 make no mention of this entity. PMID:26913877

  18. Treatment of well tubulars with gelatin

    SciTech Connect

    Lowther, F.E.

    1992-08-04

    This patent describes a method for treating a tubular in a well. It comprises: passing a mass of gelatin downward through the tubular; and passing the mass of gelating, upward in the well tubular toward the surface. This patent also describes a method of treating tubulars in a cased well having at least one string of tubing therein. It comprises positioning a mass in the annulus formed between the casing and the at least one string of tubing; and passing the mass downward in the annulus and in contact with both the inner wall of the casing and the outer wall of the tubing to deposit a protective layer on each of the walls.

  19. METHOD AND APPARATUS FOR FABRICATING TUBULAR UNITS

    DOEpatents

    Haldeman, G.W.

    1959-02-24

    A method and apparatus are described for fabricating tubular assemblies such as clad fuel elements for nuclear reactors. According to this method, a plurality of relatively short cylindrical slug-shaped members are inserted in an outer protective tubular jacket, and the assembly is passed through a reducing die to draw the outer tubular member into tight contact with the slug members, the slugs being automatically spaced with respect to each other and helium being inserted during the drawing operation to fill the spaces. The apparatus includes a pusher rod which functions to space the slugelements equidistantly by pushing on them in the direction of drawing but traveling at a slower rate than that of the tubular member.

  20. CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.

    PubMed

    Rogers, Natasha M; Zhang, Zheng J; Wang, Jiao-Jing; Thomson, Angus W; Isenberg, Jeffrey S

    2016-08-01

    Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. PMID:27259369

  1. An open tubular ion chromatograph.

    PubMed

    Yang, Bingcheng; Zhang, Min; Kanyanee, Tinakorn; Stamos, Brian N; Dasgupta, Purnendu K

    2014-12-01

    We describe an open tubular ion chromatograph (OTIC) that uses anion exchange latex coated 5 μm radius silica and 9.8 μm radius poly(methyl methacrylate) tubes and automated time/pressure based hydrodynamic injection for pL-nL scale injections. It is routinely possible to generate 50,000 plates or more (up to 150,000 plates/m, columns between 0.3 and 0.8 m have been used), and as such, fast separations are possible, comparable to or in some cases better than the current practice of IC. With an optimized admittance detector, nonsuppressed detection permits LODs of submicromolar to double digit micromolar for a variety of analytes. However, large volume injections are possible and can significantly improve on this. A variety of eluents, the use of organic modifiers, and variations of eluent pH can be used to tailor a given separation. The approach is discussed in the context of extraterrestrial exploration, especially Mars, where the existence of large amounts of perchlorate in the soil needs to be confirmed. These columns can survive drying and freezing, and small footprint, low power consumption, and simplicity make OTIC a good candidate for such a mission. PMID:25394230

  2. Sustained Oxidative Stress Causes Late Acute Renal Failure via Duplex Regulation on p38 MAPK and Akt Phosphorylation in Severely Burned Rats

    PubMed Central

    Cai, Xiaoqing; Wang, Dexin; Wu, Kaimin; Chen, Hongli; Li, Jia; Lei, Wei

    2013-01-01

    Background Clinical evidence indicates that late acute renal failure (ARF) predicts high mortality in severely burned patients but the pathophysiology of late ARF remains undefined. This study was designed to test the hypothesis that sustained reactive oxygen species (ROS) induced late ARF in a severely burned rat model and to investigate the signaling mechanisms involved. Materials and Methods Rats were exposed to 100°C bath for 15 s to induce severe burn injury (40% of total body surface area). Renal function, ROS generation, tubular necrosis and apoptosis, and phosphorylation of MAPK and Akt were measured during 72 hours after burn. Results Renal function as assessed by serum creatinine and blood urea nitrogen deteriorated significantly at 3 h after burn, alleviated at 6 h but worsened at 48 h and 72 h, indicating a late ARF was induced. Apoptotic cells and cleavage caspase-3 in the kidney went up slowly and turned into significant at 48 h and 72 h. Tubular cell ROS production shot up at 6 h and continuously rose during the 72-h experiment. Scavenging ROS with tempol markedly attenuated tubular apoptosis and renal dysfunction at 72 h after burn. Interestingly, renal p38 MAPK phosphorylation elevated in a time dependent manner whereas Akt phosphorylation increased during the first 24 h but decreased at 48 h after burn. The p38 MAPK specific inhibitor SB203580 alleviated whereas Akt inhibitor exacerbated burn-induced tubular apoptosis and renal dysfunction. Furthermore, tempol treatment exerted a duplex regulation through inhibiting p38 MAPK phosphorylation but further increasing Akt phosphorylation at 72 h postburn. Conclusions These results demonstrate that sustained renal ROS overproduction induces continuous tubular cell apoptosis and thus a late ARF at 72 h after burn in severely burned rats, which may result from ROS-mediated activation of p38 MAPK but a late inhibition of Akt phosphorylation. PMID:23349934

  3. 78 FR 37584 - U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-21

    ... Employment and Training Administration U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United States Steel Corporation, Mckeesport, Pennsylvania; Notice of Amended... workers of U.S. Steel Tubular Products, McKeesport Tubular Operations Division, a subsidiary of...

  4. Tubular Overexpression of Gremlin Induces Renal Damage Susceptibility in Mice

    PubMed Central

    Droguett, Alejandra; Krall, Paola; Burgos, M. Eugenia; Valderrama, Graciela; Carpio, Daniel; Ardiles, Leopoldo; Rodriguez-Diez, Raquel; Kerr, Bredford; Walz, Katherina; Ruiz-Ortega, Marta; Egido, Jesus; Mezzano, Sergio

    2014-01-01

    A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1) specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage progression. This

  5. Pathologic and ultrastructural changes of acute and chronic delta hepatitis in an experimentally infected chimpanzee.

    PubMed Central

    Govindarajan, S.; Fields, H. A.; Humphrey, C. D.; Margolis, H. S.

    1986-01-01

    A hepatitis B surface antigen (HBsAg) chronic carrier chimpanzee experimentally superinfected with delta virus (DV) developed chronic DV infection. Over a period of 12 months, serologic and biochemical changes were correlated with morphologic abnormalities of the liver. Severe hepatic necrosis and inflammation accompanied the initial acute episode of hepatitis on Day 35 after inoculation, followed by complete resolution of these lesions over the next 3 months. A second episode of hepatitis occurred on Day 145, and severe necrosis and inflammation recurred along with the reappearance of delta antigen in the hepatocytes. Delta antigen persisted in the liver following the second episode of hepatitis and has remained positive throughout the observation period of 1 year. During the initial acute episode, the hepatocytes exhibited foamy cytoplasmic changes resembling microvesicular fat. However, ultrastructural studies of the same cells revealed only vacuolization of the cytoplasm without evidence of fat droplets. The inflammatory infiltrate during both episodes of hepatitis demonstrated a striking predominance of macrophages over lymphocytes. Hepatocyte abnormalities observed by electron microscopy included vacuoles, proliferated endoplasmic reticulum, and tubules similar to those seen in posttransfusion non-A, non-B hepatitis. However, the tubular and reticular abnormalities coincided with delta antigen expression in liver biopsies detected by direct immunoperoxidase staining and abnormal alanine aminotransferase levels in the serum, which suggests a possible causal relationship. Nuclear abnormalities were not seen. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:3511726

  6. A clinical pathologic study of four adult cases of acute mercury inhalation toxicity

    SciTech Connect

    Kanluen, S.; Gottlieb, C.A. )

    1991-01-01

    We report four cases of fatal mercury vapor inhalation, a rare occurrence. The mercury vapor was released at a private home, where one of the occupants was smelting silver from dental amalgam containing an unknown amount of mercury. Within 24 hours of the incident, all occupants began having shortness of breath necessitating hospital admission. The clinical courses are briefly detailed; however, all included rapid deterioration with respiratory failure. Chest roentgenograms in all four cases were consistent with adult respiratory distress syndrome. All patients were treated with dimercaprol, a mercury chelator, but all died, with survival varying from 9 to 23 days postexposure. Autopsies were performed on all four patients. The lungs in all cases were heavy, firm, and airless. Histologic examination revealed severe diffuse alveolar damage, with variable amounts of fibrosis, conforming with acute lung injury in various stages of organization. Additional postmortem findings included acute proximal renal tubular necrosis, vacuolar hepatoxicity, and a spectrum of central nervous system alterations including multifocal ischemic necrosis, gliosis, and vasculitis.

  7. H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: comparison of acute and chronic toxicity in rats.

    PubMed

    Shahin, M; Moore, M R; Worrall, S; Smith, B L; Seawright, A A; Prakash, A S

    1998-09-18

    Bracken fern (Pteridium spp.) produces cancer of the urinary bladder and oesophagus in grazing animals and is a suspected human carcinogen. The carcinogenic principle ptaquiloside (PT), when activated to a dienone (APT), forms DNA adducts which eventually leads to tumor. Two groups of female Sprague-Dawley rats were given a chronic dose of 3 mg APT weekly for 10 weeks either by intravenous (i.v.) tail vein or by intragastric (i.g.) route. A third group was given a weekly dose of 6 mg of APT for 3 weeks by the i.g. route corresponding to acute dosing. Both chronic i.v. and i.g. dosed animals showed ischemic tubular necrosis in the kidney but only i.v. dosed animals developed adenocarcinomas of the mammary glands. Acutely dosed i.g. animals produced apoptotic bodies in the liver, necrosis of blood cell precursors in the bone marrow and ischemic tubular necrosis in the kidney but they did not develop tumors. No mutations were found in the H-ras and p53 genes in the mammary glands of either the i.g. rats or the tumor-bearing i.v. rats. However, the mammary glands of a fourth group of rats, which received APT by i.v. and killed before tumor development, carried Pu to Pu and Pu to Py double mutations in codons 58 and 59 of H-ras. This study indicates that the route of administration plays a role in the nature of the disease expression from ptaquiloside exposure. In addition to confirming the role of APT in the PT-induced carcinogenesis our finding suggests that activation of H-ras is an early event in the PT-carcinogenesis model. PMID:9753659

  8. Wasp sting-induced acute kidney injury

    PubMed Central

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

    2016-01-01

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

  9. A Polymeric Nanomedicine Diminishes Inflammatory Events in Renal Tubular Cells

    PubMed Central

    Ocaña-Salceda, Carlos; Sancho, Mónica; Orzáez, Mar; Messeguer, Angel; Ruiz-Ortega, Marta; Egido, Jesús; Vicent, María J.; Ortiz, Alberto; Ramos, Adrián M.

    2013-01-01

    The polyglutamic acid/peptoid 1 (QM56) nanoconjugate inhibits apoptosis by interfering with Apaf-1 binding to procaspase-9. We now describe anti-inflammatory properties of QM56 in mouse kidney and renal cell models. In cultured murine tubular cells, QM56 inhibited the inflammatory response to Tweak, a non-apoptotic stimulus. Tweak induced MCP-1 and Rantes synthesis through JAK2 kinase and NF-κB activation. Similar to JAK2 kinase inhibitors, QM56 inhibited Tweak-induced NF-κB transcriptional activity and chemokine expression, despite failing to inhibit NF-κB-p65 nuclear translocation and NF-κB DNA binding. QM56 prevented JAK2 activation and NF-κB-p65(Ser536) phosphorylation. The anti-inflammatory effect and JAK2 inhibition by QM56 were observed in Apaf-1−/− cells. In murine acute kidney injury, QM56 decreased tubular cell apoptosis and kidney inflammation as measured by down-modulations of MCP-1 and Rantes mRNA expression, immune cell infiltration and activation of the JAK2-dependent inflammatory pathway. In conclusion, QM56 has an anti-inflammatory activity which is independent from its role as inhibitor of Apaf-1 and apoptosis and may have potential therapeutic relevance. PMID:23300960

  10. Bilateral putaminal necrosis and bronopol toxicity.

    PubMed

    Trivisano, Marina; Carapelle, Elena; Martino, Tommaso; Specchio, Luigi Maria

    2015-01-01

    Among alcohols, methanol intoxication is the most frequently associated with cerebral toxicity, causing retinal damage and putaminal necrosis. This consequence is believed to be due to the transformation of methanol into formic acid. We describe the case of a patient who presented with acute impairment of consciousness and tetraparesis after she had been drinking several bottles of a topical antiseptic solution (Lysoform Medical) containing 2-bromo-2-nitro-1,3-propandiol (bronopol) among excipients, in order to lose weight during previous months. Moreover, she had been on a strict slimming diet. Soon after admission, a severe respiratory and metabolic impairment became rapidly evident, requiring an intensive care unit admission. Cerebral MRI showed the presence of bilateral putaminal necrosis. She recovered in 10 days, surprisingly, without any evident clinical neurological signs. Methanol, also bronopol, when diluted in aqueous solution, at warm temperature and/or higher pH, may release formaldehyde, which is converted into formic acid, a basal ganglia toxic compound. PMID:25697297

  11. Mechanisms of Acetaminophen-Induced Liver Necrosis

    PubMed Central

    Roberts, Dean W.; James, Laura P.

    2010-01-01

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

  12. Contribution of Proteus mirabilis urease to persistence, urolithiasis, and acute pyelonephritis in a mouse model of ascending urinary tract infection.

    PubMed

    Johnson, D E; Russell, R G; Lockatell, C V; Zulty, J C; Warren, J W; Mobley, H L

    1993-07-01

    Proteus mirabilis, a significant cause of bacteriuria and acute pyelonephritis in humans, produces urease. This high-molecular-weight, multimeric, cytoplasmic enzyme hydrolyzes urea to ammonia and carbon dioxide. To assess the role of urease in colonization, urolithiasis, and acute pyelonephritis in an animal model of ascending urinary tract infection, we compared a uropathogenic strain of P. mirabilis with its isogenic urease-negative mutant, containing an insertion mutation within ureC, the gene encoding the large subunit of the enzyme. Mice challenged transurethrally with the parent strain developed significant bacteriuria and urinary stones. The urease-negative mutant had a 50% infective dose of 2.7 x 10(9) CFU, a value more than 1,000-fold greater than that of the parent strain (2.2 x 10(6) CFU). The urease-positive parent strain reached significantly higher concentrations and persisted significantly longer in the bladder and kidney than did the mutant. Indeed, in the kidney, the parent strain increased in concentration while the mutant concentration fell so that, by 1 week, the parent strain concentration was 10(6) times that of the mutant. Similarly, the urease-positive parent produced significantly more severe renal pathology than the mutant. The initial abnormalities were in and around the pelvis and consisted of acute inflammation and epithelial necrosis. By 1 week, pyelitis was more severe, crystals were seen in the pelvis, and acute pyelonephritis, with acute interstitial inflammation, tubular epithelial cell necrosis, and in some cases abscesses, had developed. By 2 weeks, more animals had renal abscesses and radial bands of fibrosis. We conclude that the urease of P. mirabilis is a critical virulence determinant for colonization, urolithiasis, and severe acute pyelonephritis. PMID:8514376

  13. Urinary Biomarkers of Acute Kidney Injury in Patients With Liver Cirrhosis

    PubMed Central

    Ahmed, Qasem Anass; El Sayed, Farag Salama; Emad, Hamed; Mohamed, Emara; Ahmed, Bihery; Heba, Pasha

    2014-01-01

    ABSTRACT Background and aim: Acute kidney injury is a common complication in cirrhotic patients. Serum creatinine is a poor biomarker for detection of renal impairment in cirrhotic patients. The aim of this study was to evaluate Urinary Neutrophils Gelatinase-Associated Lipocalin (NGAL) and Urinary interleukin-18 (IL-18) as early biomarkers of acute kidney injury in cirrhotic patients. Patients and methods: 160 cirrhotic patients was enrolled in this study divided into 3 main groups according to presence or absence of ascites and renal impairment. Results: Significant elevation of both Urinary NGAL and Urinary IL-18 in cirrhotic patients with renal impairment especially in patients with Acute tubular necrosis (ATN) was observed. AUROC was (0.909) with (sensitivity 95.5 %, specificity 76.1) for Urinary NGAL and AUROC was (0.975), with (sensitivity 95.5 %, specificity 91.3 %) for Urinary IL-18. Conclusion: both Urinary NGAL and Urinary IL-18 can act as urinary biomarkers of acute kidney injury in cirrhotic patient PMID:24937940

  14. The regulatory T cell effector soluble fibrinogen-like protein 2 induces tubular epithelial cell apoptosis in renal transplantation.

    PubMed

    Zhao, Zitong; Yang, Cheng; Wang, Lingyan; Li, Long; Zhao, Tian; Hu, Linkun; Rong, Ruiming; Xu, Ming; Zhu, Tongyu

    2014-02-01

    Acute rejection (AR) hinders renal allograft survival. Tubular epithelial cell (TEC) apoptosis contributes to premature graft loss in AR, while the mechanism remains unclear. Soluble fibrinogen-like protein 2 (sFGL2), a novel effector of regulatory T cells (Treg), induces apoptosis to mediate tissue injury. We previously found that serum sFGL2 significantly increased in renal allograft rejection patients. In this study, the role of sFGL2 in AR was further investigated both in vivo and in vitro. The serum level of sFGL2 and the percentage of CD4(+)CD25(+)Foxp3(+) Treg in the peripheral blood were measured in renal allograft recipients with AR or stable renal function (n = 30 per group). The human TEC was stimulated with sFGL2, tumor necrosis factor (TNF)-α, or phosphate buffered saline and investigated for apoptosis in vitro. Apoptosis-associated genes expression in TEC was further assessed. Approval for this study was obtained from the Ethics Committee of Fudan University. Our results showed that the serum level of sFGL2, correlated with Treg in the peripheral blood, was significantly increased in the AR patients. In vitro, sFGL2 remarkably induced TEC apoptosis, with a significant up-regulation of proapoptotic genes, including CASP-3, CASP-8, CASP-9, CASP-10, TRADD, TNFSF10, FADD, FAS, FASLG, BAK1, BAD, BAX, and NF-KB1. However, no significant changes were observed in the expression of antiapoptotic genes, including CARD-18, NAIP, BCL2, IKBKB, and TBK1. Therefore, sFGL2, an effector of Treg, induces TEC apoptosis. Our study suggests that sFGL2 is a potential mediator in the pathogenesis of allograft rejection and provides novel insights into the role of Treg in AR. PMID:24414480

  15. Salicylate-induced proximal tubular dysfunction.

    PubMed

    Tsimihodimos, Vasilis; Psychogios, Nikolaos; Kakaidi, Varvara; Bairaktari, Eleni; Elisaf, Moses

    2007-09-01

    We describe the case of a 17-year-old girl who was admitted to our clinic for drug poisoning. Twelve hours after the ingestion of 25 tablets of aspirin (12.5 g of acetylsalicylic acid), the patient had a generalized proximal tubular dysfunction characterized by glucosuria (in the face of normal serum glucose levels), proteinuria, and uric acid wasting. Further characterization of the tubular dysfunction using high-resolution proton nuclear magnetic resonance spectroscopy of the urine showed a pattern consistent with proximal tubular injury. An important characteristic of the salicylate-induced proximal tubular dysfunction in our patient was its rapid reversibility. A trend toward normalization of fractional excretion values of electrolytes was observed 2 days after ingestion. Determination of serum and urine metabolites and spectroscopy of urine 15 days later showed no evidence of tubular dysfunction. The mechanisms potentially implicated in the pathogenesis of salicylate-induced Fanconi syndrome are discussed and a brief review of the relevant literature is provided. PMID:17720526

  16. Cholestatic jaundice, acute kidney injury and acute pancreatitis secondary to the recreational use of methandrostenolone: a case report

    PubMed Central

    2011-01-01

    Introduction Over the last few years the use of anabolic steroids has become increasingly common amongst amateur athletes and for aesthetic purposes. As a result, the adverse events related to their use are being seen more frequently. Methandrostenolone is an anabolic steroid which is widely available and has been used for both performance enhancement and aesthetic purposes. This drug has also been reported to cause cholestasis of the intra-hepatic bile ducts resulting in elevated aminotransferases, hyperbilirubinemia and clinical jaundice. However, to the best of our knowledge this agent has not been previously reported to cause pancreatitis or acute kidney injury. Case presentation In this paper, we report the case of a 50-year-old man of Indian descent who presented with a six week history of diffuse abdominal pain, anorexia and weight loss following an eight week cycle of methandrostenolone use. At initial presentation, his lipase level was 785 U/L, bilirubin was 922 μmol/L and creatinine was 200 U/L while his aspartate aminotransferase and alanine aminotransferase levels were only mildly elevated at 61 U/L and 56 U/L respectively. His lipase peaked on day nine at >3000 U/L whilst his creatinine level was 299 U/L. Imaging was consistent with acute pancreatitis while a liver biopsy was consistent with intra-hepatic cholestasis and a kidney biopsy revealed evidence of acute tubular necrosis. Conclusion Both acute pancreatitis and acute kidney injury have rarely been reported with anabolic steroid use and they have not been previously reported to occur in the same patient. This case demonstrates some potentially new and serious adverse consequences occurring with the use of anabolic steroids, of which physicians need to be aware. PMID:21470406

  17. Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

    SciTech Connect

    Wu, Cheng Tien; Weng, Te I.; Chen, Li Ping; Chiang, Chih Kang; Liu, Shing Hwa

    2013-01-01

    Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

  18. Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Facilitate Tubular Epithelial Cell Dedifferentiation and Growth via Hepatocyte Growth Factor Induction

    PubMed Central

    Wu, Shuai; Zou, Xiang-yu; Zhang, Guang-yuan; Gu, Di; Miao, Shuai; Zhu, Ying-jian; Sun, Jie; Du, Tao

    2015-01-01

    During acute kidney injury (AKI), tubular cell dedifferentiation initiates cell regeneration; hepatocyte growth factor (HGF) is involved in modulating cell dedifferentiation. Mesenchymal stem cell (MSC)-derived microvesicles (MVs) deliver RNA into injured tubular cells and alter their gene expression, thus regenerating these cells. We boldly speculated that MVs might induce HGF synthesis via RNA transfer, thereby facilitating tubular cell dedifferentiation and regeneration. In a rat model of unilateral AKI, the administration of MVs promoted kidney recovery. One of the mechanisms of action is the acceleration of tubular cell dedifferentiation and growth. Both in vivo and in vitro, rat HGF expression in damaged rat tubular cells was greatly enhanced by MV treatment. In addition, human HGF mRNA present in MVs was delivered into rat tubular cells and translated into the HGF protein as another mechanism of HGF induction. RNase treatment abrogated all MV effects. In the in vitro experimental setting, the conditioned medium of MV-treated injured tubular cells, which contains a higher concentration of HGF, strongly stimulated cell dedifferentiation and growth, as well as Erk1/2 signaling activation. Intriguingly, these effects were completely abrogated by either c-Met inhibitor or MEK inhibitor, suggesting that HGF induction is a crucial contributor to the acceleration of cell dedifferentiation and growth. All these findings indicate that MV-induced HGF synthesis in damaged tubular cells via RNA transfer facilitates cell dedifferentiation and growth, which are important regenerative mechanisms. PMID:25793303

  19. Tubular Colonic Duplication Presenting as Rectovestibular Fistula

    PubMed Central

    Bendre, Pradnya; D'souza, Flavia; Ramchandra, Mukunda; Nage, Amol; Palse, Nitin

    2015-01-01

    Complete colonic duplication is a very rare congenital anomaly that may have different presentations according to its location and size. Complete colonic duplication can occur in about 15% of all gastrointestinal duplications. Double termination of tubular colonic duplication in the perineum is even more uncommon. We present a case of a Y-shaped tubular colonic duplication which presented with a rectovestibular fistula and a normal anus. Radiological evaluation and initial exploration for sigmoidostomy revealed duplicated colons with a common vascular supply. Endorectal mucosal resection of theduplicated distal segment till the colostomy site with division of the septum of the proximal segment and colostomy closure proved curative without compromise of the continence mechanism. Tubular colonic duplication should always be ruled out when a diagnosis of perineal canal is considered in cases of vestibular fistula alongwith a normal anus. PMID:26473141

  20. Tubular Colonic Duplication Presenting as Rectovestibular Fistula.

    PubMed

    Karkera, Parag J; Bendre, Pradnya; D'souza, Flavia; Ramchandra, Mukunda; Nage, Amol; Palse, Nitin

    2015-09-01

    Complete colonic duplication is a very rare congenital anomaly that may have different presentations according to its location and size. Complete colonic duplication can occur in about 15% of all gastrointestinal duplications. Double termination of tubular colonic duplication in the perineum is even more uncommon. We present a case of a Y-shaped tubular colonic duplication which presented with a rectovestibular fistula and a normal anus. Radiological evaluation and initial exploration for sigmoidostomy revealed duplicated colons with a common vascular supply. Endorectal mucosal resection of theduplicated distal segment till the colostomy site with division of the septum of the proximal segment and colostomy closure proved curative without compromise of the continence mechanism. Tubular colonic duplication should always be ruled out when a diagnosis of perineal canal is considered in cases of vestibular fistula alongwith a normal anus. PMID:26473141

  1. [Renal ultrasound in fat necrosis].

    PubMed

    Tizki, S; Lasry, F; Elftoiki, F Z; Hadj Khalifa, H; Itri, M; Khadir, K; Benchikhi, H

    2013-07-01

    Subcutaneous fat necrosis is an uncommon disease that may be complicated with potentially fatal hypercalcemia or with nephrocalcinosis. We report on the case of a patient with a history of significant perinatal asphyxia, hospitalized for a urinary tract infection. Lesions of subcutaneous fat necrosis were noted, with asymptomatic hypercalcemia at 3.9mmol/L. A renal ultrasound was performed and showed echogenic medullary pyramids bilaterally, consistent with nephrocalcinosis and left nephrolithiasis. The treatment of hypercalcemia included hyperhydration, a diuretic and corticosteroids. Progression was characterized by the total regression of skin lesions and normalization of serum calcium. Hypercalcemia is a rare complication of subcutaneous fat necrosis. It develops within days to weeks after the appearance of skin lesions. Nephrocalcinosis appears after several weeks or months. Hypercalcemia must be treated in due time to avoid the impact on the kidney. PMID:23726682

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

    PubMed Central

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

    2015-01-01

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

  3. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-08-23

    B Acute Lymphoblastic Leukemia; Bone Necrosis; Central Nervous System Leukemia; Cognitive Side Effects of Cancer Therapy; Neurotoxicity Syndrome; Pain; Testicular Leukemia; Therapy-Related Toxicity; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  4. Widespread marrow necrosis during pregnancy

    SciTech Connect

    Knickerbocker, W.J.; Quenville, N.F.

    1982-11-01

    Recently, a 22-year-old Caucasian female was referred to our Hospital two days post-partum. She had been feeling unwell during the last few days of her pregnancy and complained of multiple aches and pains, worst in the abdomen and lower back. Her admission platelet count was severely depressed and a bone biopsy showed extensive marrow necrosis with viable bony trabeculae. There was no evidence of vasculitis, vascular thrombosis, or malignancy. Widespread marrow necrosis in pregnancy followed by recovery, to our knowledge, has not been previously reported.

  5. Tubular solid oxide fuel cell current collector

    DOEpatents

    Bischoff, Brian L.; Sutton, Theodore G.; Armstrong, Timothy R.

    2010-07-20

    An internal current collector for use inside a tubular solid oxide fuel cell (TSOFC) electrode comprises a tubular coil spring disposed concentrically within a TSOFC electrode and in firm uniform tangential electrical contact with the electrode inner surface. The current collector maximizes the contact area between the current collector and the electrode. The current collector is made of a metal that is electrically conductive and able to survive under the operational conditions of the fuel cell, i.e., the cathode in air, and the anode in fuel such as hydrogen, CO, CO.sub.2, H.sub.2O or H.sub.2S.

  6. Deployable and retractable telescoping tubular structure development

    NASA Technical Reports Server (NTRS)

    Thomson, M. W.

    1994-01-01

    A new deployable and retractable telescoping boom capable of high deployed stiffness and strength is described. Deployment and retraction functions are controlled by simple, reliable, and fail-safe latches between the tubular segments. The latch and a BI-STEM (Storable Tubular Extendible Member) actuator work together to eliminate the need for the segments to overlap when deployed. This yields an unusually lightweight boom and compact launch configuration. An aluminum space-flight prototype with three joints displays zero structural deadband, low hysteresis, and high damping. The development approach and difficulties are discussed. Test results provide a joint model for sizing flight booms of any diameter and length.

  7. Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice

    PubMed Central

    Hudcovic, T; Kolinska, J; Klepetar, J; Stepankova, R; Rezanka, T; Srutkova, D; Schwarzer, M; Erban, V; Du, Z; Wells, J M; Hrncir, T; Tlaskalova-Hogenova, H; Kozakova, H

    2012-01-01

    One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms – bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression. PMID:22236013

  8. Acute Effect of Intravenous Administration of Magnesium Sulfate on Serum Levels of Interleukin-6 and Tumor Necrosis Factor-α in Patients Undergoing Elective Coronary Bypass Graft With Cardiopulmonary Bypass

    PubMed Central

    Aryana, Parastou; Rajaei, Samira; Bagheri, Abdolhamid; Karimi, Forouzan; Dabbagh, Ali

    2014-01-01

    Background: Cardiovascular problems are among the most common health issues. A considerable number of cardiac patients undergo cardiac surgery, and coronary artery disease patients constitute about two-thirds of all these surgeries. The application of cardiopulmonary bypass (CBP) usually results in some untoward effects. Objectives: Studies have suggested magnesium sulfate (MgSO4) as an anti-inflammatory agent in a coronary artery bypass graft (CABG). This study aimed to assess the effect of an IV MgSO4 infusion during elective CABG (with CBP) on the blood levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Materials and Methods: During a 12 month period, after review board approval and based on inclusion and exclusion criteria, 90 patients were selected and entered randomly into one of the two study groups (MgSO4 or placebo). Anesthesia, surgery and CBP were performed in exactly the same way, except for the use of MgSO4 or a placebo. Both preoperative and postoperative plasma levels of IL-6 and TNF-α were checked and compared between the two groups using an ELISA. Results: There was no difference found between the two groups with regard to; gender, basic variables, Ejection Fraction (EF), CBP time and aortic cross-clamp time. The preoperative levels of IL-6 and TNF-α were not different; however, their postoperative levels were significantly higher in the placebo group (P value = 0.01 for IL-6 and 0.005 for TNF-α). Conclusions: This study showed that MgSO4 infusion could suppress part of the inflammatory response after CABG with CBP. This was demonstrated by decreased levels of interleukin-6 and TNF-α in postoperative serum levels in elective CABG with CBP. PMID:25237633

  9. Tubularized Penile-Flap Urethroplasty Using a Fasciocutaneous Random Pedicled Flap for Recurrent Anterior Urethral Stricture

    PubMed Central

    Lee, Byung Kwon

    2012-01-01

    This report describes the use of a tubularized random flap for the curative treatment of recurrent anterior urethral stricture. Under the condition of pendulous lithotomy and suprapubic cystostomy, the urethral stricture was removed via a midline ventral penile incision followed by elevation of the flap and insertion of an 18-Fr catheter. Subcutaneous buried interrupted sutures were used to reapproximate the waterproof tubularized neourethra and to coapt with the neourethra and each stump of the urethra, first proximally and then distally. The defect of the penile shaft was covered by advancement of the surrounding scrotal flap. The indwelling catheter was maintained for 21 days. A 9 month postoperative cystoscopy showed no flap necrosis, no mechanical stricture, and no hair growth on the lumen of the neourethra. The patient showed no voiding discomfort 6 months after the operation. The advantages of this procedure are the lack of need for microsurgery, shortening of admission, the use of only spinal anesthesia (no general anesthesia), and a relatively short operative time. The tubularized unilateral penile fasciocutaneous flap should be considered an option for initial flap urethroplasty as a curative technique. PMID:22783537

  10. Familial myopathy with tubular aggregates associated with abnormal pupils.

    PubMed

    Shahrizaila, Nortina; Lowe, James; Wills, Adrian

    2004-09-28

    The authors describe familial tubular aggregate myopathy associated with abnormal pupils. Four family members from two generations had myopathy and pupillary abnormalities. The myopathologic findings consisted of tubular aggregates in many fibers but predominantly type I fibers. PMID:15452313

  11. Efficacy of extracorporeal albumin dialysis for acute kidney injury due to cholestatic jaundice nephrotoxicity.

    PubMed

    Sens, Florence; Bacchetta, Justine; Rabeyrin, Maud; Juillard, Laurent

    2016-01-01

    We report a case of a 37-year-old man with Maturity Onset Diabetes of the Youth (MODY) type 5, admitted for an episode of cholestasis and a simultaneous acute kidney injury (AKI). Chronic liver disease was due to a mutation in the transcription factor 2 (TCF2) gene, thus highlighting the need for a close liver follow-up in these patients. AKI was attributed to a cholemic nephropathy based on the following rationale: (1) alternative diagnoses were actively ruled out; (2) the onset of AKI coincided with the onset of severe hyperbilirubinaemia; (3) renal pathology showed large bile tubular casts and a marked tubular necrosis and (4) creatinine serum dramatically decreased when bilirubin levels improved after the first sessions of extracorporeal albumin dialysis (ECAD), thus suggesting its role in renal recovery. Even though cholestasis can precipitate renal injury, the diagnosis of cholemic nephropathy could require a renal biopsy at times. Future studies should confirm the benefits of ECAD in cholemic nephropathy. PMID:27389722

  12. Circulating plasma factors induce tubular and glomerular alterations in septic burns patients

    PubMed Central

    Mariano, Filippo; Cantaluppi, Vincenzo; Stella, Maurizio; Romanazzi, Giuseppe Mauriello; Assenzio, Barbara; Cairo, Monica; Biancone, Luigi; Triolo, Giorgio; Ranieri, V Marco; Camussi, Giovanni

    2008-01-01

    Background Severe burn is a systemic illness often complicated by sepsis. Kidney is one of the organs invariably affected, and proteinuria is a constant clinical finding. We studied the relationships between proteinuria and patient outcome, severity of renal dysfunction and systemic inflammatory state in burns patients who developed sepsis-associated acute renal failure (ARF). We then tested the hypothesis that plasma in these patients induces apoptosis and functional alterations that could account for proteinuria and severity of renal dysfunction in tubular cells and podocytes. Methods We studied the correlation between proteinuria and indexes of systemic inflammation or renal function prospectively in 19 severe burns patients with septic shock and ARF, and we evaluated the effect of plasma on apoptosis, polarity and functional alterations in cultured human tubular cells and podocytes. As controls, we collected plasma from 10 burns patients with septic shock but without ARF, 10 burns patients with septic shock and ARF, 10 non-burns patients with septic shock without ARF, 10 chronic uremic patients and 10 healthy volunteers. Results Septic burns patients with ARF presented a severe proteinuria that correlated to outcome, glomerular (creatinine/urea clearance) and tubular (fractional excretion of sodium and potassium) functional impairment and systemic inflammation (white blood cell (WBC) and platelet counts). Plasma from these patients induced a pro-apoptotic effect in tubular cells and podocytes that correlated with the extent of proteinuria. Plasma-induced apoptosis was significantly higher in septic severe burns patients with ARF with respect to those without ARF or with septic shock without burns. Moreover, plasma from septic burns patients induced an alteration of polarity in tubular cells, as well as reduced expression of the tight junction protein ZO-1 and of the endocytic receptor megalin. In podocytes, plasma from septic burns patients increased

  13. Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice.

    PubMed

    Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi; Nishikawa, Yoshifumi

    2016-03-01

    In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality. PMID:26755155

  14. Proximal tubular NHEs: sodium, protons and calcium?

    PubMed Central

    Alexander, R. Todd; Dimke, Henrik; Cordat, Emmanuelle

    2016-01-01

    Na+/H+ exchange activity in the apical membrane of the proximal tubule is fundamental to the reabsorption of Na+ and water from the filtrate. The role of this exchange process in bicarbonate reclamation and, consequently, the maintenance of acid-base homeostasis has been appreciated for at least half a century and remains a pillar of renal tubular physiology. More recently, apical Na+/H+ exchange, mediated by Na+/H+ exchanger isoform 3 (NHE3), has been implicated in proximal tubular reabsorption of Ca2+ and Ca2+ homeostasis in general. Overexpression of NHE3 increased paracellular Ca2+ flux in a proximal tubular cell model. Consistent with this observation, mice with genetic deletion of Nhe3 have a noticable renal Ca2+ leak. These mice also display decreased intestinal Ca2+ uptake and osteopenia. This review highlights the traditional roles of proximal tubular Na+/H+ exchange and summarizes recent novel findings implicating the predominant isoform, NHE3, in Ca2+ homeostasis. PMID:23761670

  15. Comparative physiology of renal tubular transport mechanisms.

    PubMed Central

    Long, S.; Giebisch, G.

    1979-01-01

    This manuscript discusses current concepts of glomerular filtration and tubular transport of sodium, water, potassium, and urinary acidification by vertebrate kidneys in a comparative context. Work in mammalian and amphibian nephrons receives major emphasis due to our interest in application of new techniques for investigation of cellular mechanisms; when available, data from other vertebrate classes are discussed. Images FIG. 3 PMID:395765

  16. [Hypokalemic pareses secondary to renal tubular acidosis].

    PubMed

    Gøransson, L G; Apeland, T; Omdal, R

    2000-01-30

    A 24 year old woman presented with flaccid paralysis, severe hypokalaemia and hyperchloremia, metabolic acidosis. Immunological tests and labial glandular biopsy indicated primary Sjögren's syndrome as the underlying cause of her distal renal tubular acidosis. The patient recovered after alkali and potassium substitution and was put on oral treatment with potassium citrate. PMID:10827521

  17. Tubular copper thrust chamber design study

    NASA Technical Reports Server (NTRS)

    Masters, A. I.; Galler, D. E.

    1992-01-01

    The use of copper tubular thrust chambers is particularly important in high performance expander cycle space engines. Tubular chambers have more surface area than flat wall chambers, and this extra surface area provides enhanced heat transfer for additional energy to power the cycle. This paper was divided into two sections: (1) a thermal analysis and sensitivity study; and (2) a preliminary design of a selected thrust chamber configuration. The thermal analysis consisted of a statistical optimization to determine the optimum tube geometry, tube booking, thrust chamber geometry, and cooling routing to achieve the maximum upper limit chamber pressure for a 25,000 pound thrust engine. The preliminary design effort produced a layout drawing of a tubular thrust chamber that is three inches shorter than the Advanced Expander Test Bed (AETB) milled channel chamber but is predicted to provide a five percent increase in heat transfer. Testing this chamber in the AETB would confirm the inherent advantages of tubular chamber construction and heat transfer.

  18. Tubular Membrane Plant-Growth Unit

    NASA Technical Reports Server (NTRS)

    Dreschel, Thomas W.

    1992-01-01

    Hydroponic system controls nutrient solution for growing crops in space. Pump draws nutrient solution along inside of tubular membrane in pipe from reservoir, maintaining negative pressure in pipe. Roots of plants in slot extract nutrient through membrane within pipe. Crop plants such as wheat, rice, lettuce, tomatoes, soybeans, and beans grown successfully with system.

  19. Acute oxalate nephropathy associated with orlistat

    PubMed Central

    Humayun, Youshay; Ball, Kenneth C.; Lewin, Jack R.; Lerant, Anna A.; Fülöp, Tibor

    2016-01-01

    Background: Obesity is a major world-wide epidemic which has led to a surge of various weight loss-inducing medical or surgical treatments. Orlistat is a gastrointestinal lipase inhibitor used as an adjunct treatment of obesity and type 2 diabetes mellitus to induce clinically significant weight loss via fat malabsorption. Case Presentation: We describe a case of a 76-year-old female with past medical history of chronic kidney disease (baseline serum creatinine was 1.5-2.5 mg/dL), hypertension, gout and psoriatic arthritis, who was admitted for evaluation of elevated creatinine, peaking at 5.40 mg/dL. She was started on orlistat 120 mg three times a day six weeks earlier. Initial serologic work-up remained unremarkable. Percutaneous kidney biopsy revealed massive calcium oxalate crystal depositions with acute tubular necrosis and interstitial inflammation. Serum oxalate level returned elevated at 45 mm/l (normal <27). Timed 24-hour urine collection documented increased oxalate excretion repeatedly (54-96 mg/24 hour). After five renal dialysis sessions in eighth days she gradually regained her former baseline kidney function with creatinine around 2 mg/dL. Given coexisting proton-pump inhibitor therapy, only per os calcium-citrate provided effective intestinal oxalate chelation to control hyperoxaluria. Conclusions: Our case underscores the potential of medically induced fat malabsorption to lead to an excessive oxalate absorption and acute kidney injury (AKI), especially in subjects with pre-existing renal impairment. Further, it emphasizes the importance of kidney biopsy to facilitate early diagnosis and treatment. PMID:27152294

  20. 78 FR 14361 - U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ... Employment and Training Administration U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United States Steel Corporation, Mckeesport, PA; Notice of Initiation of...) filed on December 20, 2012 on behalf of workers of U.S. Steel Tubular Products, McKeesport...

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

    PubMed

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

    2013-10-01

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

  2. Out of the TWEAKlight: Elucidating the Role of Fn14 and TWEAK in Acute Kidney Injury.

    PubMed

    Sanz, Ana B; Ruiz-Andres, Olga; Sanchez-Niño, Maria Dolores; Ruiz-Ortega, Marta; Ramos, Adrian M; Ortiz, Alberto

    2016-05-01

    Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a tumor necrosis factor superfamily cytokine that activates the fibroblast growth factor-inducible-14 (Fn14) receptor. Functional studies have established a role of TWEAK/Fn14 in experimental acute kidney injury (AKI) and the AKI to chronic kidney disease transition through actions on tubular cells and renal fibroblasts. The renal cell expression of TWEAK and Fn14 is increased in human and experimental AKI and targeting TWEAK or Fn14 by genetic means or neutralizing antibodies was protective in kidney injury induced by folic acid overdose, ischemia-reperfusion, or unilateral ureteral obstruction. TWEAK/Fn14 targeting preserved renal function, and reduced tubular cell injury and death, nuclear factor-κB activation, chemokine expression, inflammatory cell infiltration by macrophages and T cells, myofibroblast numbers, and extracellular matrix deposition, while preserving the expression of the anti-aging factor klotho and the mitochondrial regulator Peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1α), as well as of PGC1α-dependent genes. The beneficial in vivo effects of TWEAK/Fn14 targeting are consistent with known actions of TWEAK on kidney cells. We review the literature on TWEAK and AKI and propose further avenues of research to unravel the contribution of TWEAK to kidney injury. Although a randomized clinical trial of neutralizing anti-TWEAK antibodies for lupus nephritis recently was terminated for futility, AKI represents a potential target for clinical development because it is potentially lethal and, as opposed to severe lupus nephritis, is very common, lacks effective therapy, and is not autoimmune in nature. PMID:27339384

  3. Kielin/Chordin-Like Protein Attenuates both Acute and Chronic Renal Injury

    PubMed Central

    Soofi, Abdul; Zhang, Peng

    2013-01-01

    The secreted kielin/chordin-like (KCP) protein, one of a family of cysteine-rich proteins, suppresses TGF-β signaling by sequestering the ligand from its receptor, but it enhances bone morphogenetic protein (BMP) signaling by promoting ligand-receptor interactions. Given the critical roles for TGF-β and BMP proteins in enhancing or suppressing renal interstitial fibrosis, respectively, we examined whether secreted KCP could attenuate renal fibrosis in mouse models of chronic and acute disease. Transgenic mice that express KCP in adult kidneys showed significantly less expression of collagen IV, α-smooth muscle actin, and other markers of disease progression in the unilateral ureteral obstruction model of renal interstitial fibrosis. In the folic acid nephrotoxicity model of acute tubular necrosis, mice expressing KCP survived high doses of folic acid that were lethal for wild-type mice. With a lower dose of folic acid, mice expressing KCP exhibited improved renal recovery compared with wild-type mice. Thus, these data suggest that extracellular regulation of the TGF-β/BMP signaling axis by KCP, and by extension possibly other cysteine-rich domain proteins, can attenuate both acute and chronic renal injury. PMID:23539757

  4. [Latest advances in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2015-09-01

    The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition. PMID:26520203

  5. Renal tubular acidosis complicated with hypokalemic periodic paralysis.

    PubMed

    Chang, Y C; Huang, C C; Chiou, Y Y; Yu, C Y

    1995-07-01

    Three Chinese girls with hypokalemic periodic paralysis secondary to different types of renal tubular acidosis are presented. One girl has primary distal renal tubular acidosis complicated with nephrocalcinosis. Another has primary Sjögren syndrome with distal renal tubular acidosis, which occurs rarely with hypokalemic periodic paralysis in children. The third has an isolated proximal renal tubular acidosis complicated with multiple organ abnormalities, unilateral carotid artery stenosis, respiratory failure, and consciousness disturbance. The diagnostic evaluation and emergent and prophylactic treatment for these three types of renal tubular acidosis are discussed. PMID:7575850

  6. Pancreatic necrosis: results of necrosectomy, packing, and ultimate closure over drains.

    PubMed Central

    Branum, G; Galloway, J; Hirchowitz, W; Fendley, M; Hunter, J

    1998-01-01

    OBJECTIVE: The treatment of pancreatic necrosis at a tertiary referral center was reviewed to effect better patient outcome. SUMMARY BACKGROUND DATA: Pancreatic necrosis is a devastating disease that leads to death in 10% to 50% of cases. Infected necrosis is particularly deadly because 80% of deaths from necrosis are due to infection or its complications. Therapeutic strategies center on aggressive support of organ systems and prevention and treatment of infectious complications. METHODS: Records of all patients who underwent pancreatic necrosectomy from 1990 to 1996 at Emory University Hospital were reviewed. Patients with infected necrosis were debrided as soon as the diagnosis was made. Reoperation for completion necrosectomy with ultimate closure over lavage catheters was performed as necessary. RESULTS: Of the 244 patients admitted with acute pancreatitis in the study period, 50 underwent pancreatic debridement. The mean age was 52 years, and 74% of patients were transferred from other institutions. Eighty-four percent of patients had infected necrosis, and all patients underwent sequential debridement with eventual closure over drains. Organ failure occurred in 72% of cases, and the overall mortality rate was 12%. The mean length of stay was 54 days. CONCLUSIONS: The management of pancreatic necrosis demands the allocation of extensive resources. An aggressive operative strategy of multiple debridements with ultimate closure over drains can lead to a low mortality rate in patients with this complex disease, but the determination of when to explore patients with sterile necrosis remains difficult. PMID:9637550

  7. [Talus necrosis and its treatment].

    PubMed

    Trauth, J; Bläsius, K

    1988-08-01

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

  8. Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans

    NASA Technical Reports Server (NTRS)

    Nagashima, K.; Wu, J.; Kavouras, S. A.; Mack, G. W.

    2001-01-01

    We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.

  9. Hypokalemic periodic paralysis in Sjogren's syndrome secondary to distal renal tubular acidosis.

    PubMed

    Yılmaz, Hakkı; Kaya, Mustafa; Özbek, Mustafa; ÜUreten, Kemal; Safa Yıldırım, İ

    2013-07-01

    We report a 53-year-old Turkish female presented with progressive weakness and mild dyspnea. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis. The urinary anion gap was positive in the presence of acidemia, thus she was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:3,200 and positive antibodies to SSA and SSB. Schirmer's test was abnormal. Autoimmune and other tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy, and corticosteroids. Primary SS could be a differential in women with acute weakness and hypokalemia. PMID:22212410

  10. Glomerular tubular balance: mediation by luminal hypotonicity.

    PubMed

    Häberle, D A; Müller, U; Nagel, W

    1989-01-01

    Late proximal rat tubular segments were microperfused with slightly hypo- or hypertonic artificial late proximal tubular fluid (ATF) at low (11-13 nl/min) or high (30-38 nl/min) perfusion rates. Volume reabsorption, net chloride and solute reabsorption were measured as a function of length. In addition, the transepithelial resistance and voltage (Vte) were measured as a function of the applied osmotic gradient. Hypertonic solutions equilibrated to isotonicity by solute outflow rather than water influx. With hypertonic ATF the lumen positive Vte was decreased compared with free flow or with hypotonic ATF. The resistance was not significantly different between the different groups. In contrast to hypotonic ATF, hypertonic or isotonic ATF was not significantly reabsorbed. In addition, hypotonic ATF maintained its hypotonicity along the perfused segments. Its reabsorption was flow-dependent. Hypotonicity appeared to enhance solute reabsorption. PMID:2725432