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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 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

  5. 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

  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. 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

  8. 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

  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. 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

  10. 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

  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

    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 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

  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. 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

  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. 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

  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. 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

  15. 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

  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. 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

  8. 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

  9. 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

  10. 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

  11. 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

  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. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  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

    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

  6. 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

  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. 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

  10. 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

  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. 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

  9. 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

  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 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

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

    PubMed

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

    2015-03-01

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

  14. 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. 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

  11. 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

  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. 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

  8. 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

  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. 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

  15. [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

  16. 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.

  17. 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

  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. 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

  5. [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

  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. Pattern Selection in Growing Tubular Tissues

    NASA Astrophysics Data System (ADS)

    Ciarletta, P.; Balbi, V.; Kuhl, E.

    2014-12-01

    Tubular organs display a wide variety of surface morphologies including circumferential and longitudinal folds, square and hexagonal undulations, and finger-type protrusions. Surface morphology is closely correlated to tissue function and serves as a clinical indicator for physiological and pathological conditions, but the regulators of surface morphology remain poorly understood. Here, we explore the role of geometry and elasticity on the formation of surface patterns. We establish morphological phase diagrams for patterns selection and show that increasing the thickness or stiffness ratio between the outer and inner tubular layers induces a gradual transition from circumferential to longitudinal folding. Our results suggest that physical forces act as regulators during organogenesis and give rise to the characteristic circular folds in the esophagus, the longitudinal folds in the valves of Kerckring, the surface networks in villi, and the crypts in the large intestine.

  11. Tubular lap joints for wind turbine applications

    SciTech Connect

    Reedy, E.D. Jr.; Guess, T.R.

    1990-01-01

    A combined analytical/experimental study of the strength of thick- walled, adhesively bonded PMMA-to-aluminum and E-glass/epoxy composite-to-aluminum tubular lap joints under axial load has been conducted. Test results include strength and failure mode data. Moreover, strain gages placed along the length of the outer tubular adherend characterize load transfer from one adherend to the other. The strain gage data indicate that load transfer is nonuniform and that the relatively compliant PMMA has the shorter load transfer length. Strains determined by a finite element analysis of the tested joints are in excellent agreement with those measured. Calculated bond stresses are highest in the region of observed failure, and extensive bond yielding is predicted in the E- glass/epoxy composite-to-aluminum joint prior to joint failure. 4 refs., 13 figs., 1 tab.

  12. Tubular Heart Pumping Mechanisms in Ciona Intestinalis

    NASA Astrophysics Data System (ADS)

    Battista, Nicholas; Miller, Laura

    2015-11-01

    In vertebrate embryogenesis, the first organ to form is the heart, beginning as a primitive heart tube. However, many invertebrates have tubular hearts from infancy through adulthood. Heart tubes have been described as peristaltic and impedance pumps. Impedance pumping assumes a single actuation point of contraction, while traditional peristalsis assumes a traveling wave of actuation. In addition to differences in flow, this inherently implies differences in the conduction system. It is possible to transition from pumping mechanism to the other with a change in the diffusivity of the action potential. In this work we consider the coupling between the fluid dynamics and electrophysiology of both mechanisms, within a basal chordate, the tunicate. Using CFD with a neuro-mechanical model of tubular pumping, we discuss implications of the both mechanisms. Furthermore, we discuss the implications of the pumping mechanism on evolution and development.

  13. 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

  14. Latch ring for connecting tubular member

    SciTech Connect

    Milberger, L.J.

    1991-06-04

    This patent describes a device for releasably locking an inner member well bore of a tubular outer member, comprising a combination of a grooved inner member profile formed on the exterior of the inner member; a grooved outer member profile formed in the bore of the outer member; a split ring carried by the inner member the ring having a grooved outer profile on its exterior mates with the outer member profile; and the inner member being axially movable.

  15. Self-Cleaning Tubular-Membrane Module

    NASA Technical Reports Server (NTRS)

    Sarbolouki, M. N.

    1983-01-01

    Tubular membranes made self-cleaning with aid of flow reversing valve. Sponge balls scrub membrane surfaces as they travel inside membrane tubes. A four-way flow-reversal valve automatically reverses flow in tubes at preset intervals so sponge balls reciprocate along tubes. Baskets at ends of tubes prevent sponges from escaping. Automatic cleaning feature added to existing membrane processing equipment with minimal modifications.

  16. Tubular electric heater with a thermocouple assembly

    DOEpatents

    House, R.K.; Williams, D.E.

    1975-08-01

    This patent relates to a thermocouple or other instrumentation which is installed within the walls of a tubular sheath surrounding a process device such as an electric heater. The sheath comprises two concentric tubes, one or both of which have a longitudinal, concave crease facing the other tube. The thermocouple is fixedly positioned within the crease and the outer tube is mechanically reduced to form an interference fit onto the inner tube. (auth)

  17. Evaluation of autologous bone marrow-derived mesenchymal stem cells on renal regeneration after experimentally induced acute kidney injury in dogs.

    PubMed

    Lim, Chae-Young; Han, Jae-Ik; Kim, Seung-Gon; Lee, Chang-Min; Park, Hee-Myung

    2016-02-01

    OBJECTIVE To evaluate the usefulness of autologous bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for the treatment of dogs with experimentally induced acute kidney injury. ANIMALS 6 healthy dogs. PROCEDURES After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), dogs immediately received saline (0.9% NaCl) solution (10 mL; n = 3) or BM-MSCs (1 × 10(6) cells/kg in 10 mL of saline solution; 3) IV. A CBC, serum biochemical analysis, and urinalysis were performed for each dog before administration of cisplatin and on days 1 through 4. Glomerular filtration rate was determined for all dogs on days -7 and 2; BM-MSC tracking by MRI was performed on BM-MSC-treated dogs on days -14 and 4. After sample collection and BM-MSC tracking on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analysis, and cytokine profiling via reverse transcriptase PCR assays. RESULTS Kidney tissue from both groups had mononuclear inflammatory cell infiltration, tubular necrosis, dilated tubules, and glomerular damage. However, there was less fibrotic change and increased proliferation of renal tubular epithelial cells in the BM-MSC-treated dogs, compared with findings for the control dogs. Expressions of tumor necrosis factor-α and transforming growth factor-β were lower in the BM-MSC-treated group, compared with findings for the control group. Laboratory data revealed no improvement in the renal function in BM-MSC-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study suggested that autologous BM-MSCs may accelerate renal regeneration after experimentally induced acute kidney injury in dogs. (Am J Vet Res 2016;77:208-217). PMID:27027716

  18. Blocking TGF-β Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRβ+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats

    PubMed Central

    Pozdzik, Agnieszka A.; Giordano, Laetitia; Li, Gang; Antoine, Marie-Hélène; Quellard, Nathalie; Godet, Julie; De Prez, Eric; Husson, Cécile; Declèves, Anne-Emilie; Arlt, Volker M.; Goujon, Jean-Michel; Brochériou-Spelle, Isabelle; Ledbetter, Steven R.; Caron, Nathalie; Nortier, Joëlle L.

    2016-01-01

    Background The platelet-derived growth factor receptor β (PDGFRβ)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target. Aims In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ) inhibition in a rat model of AAN. Materials and Methods Neutralizing anti-TGFβ antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily. Results At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro. Conclusions The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation. PMID:27379382

  19. Liver necrosis and photosensitisation in cattle after eating Persicaria lapathifolia (pale knotweed) and Persicaria orientalis (Prince's feather).

    PubMed

    Lugton, I W; Woolacott, J

    2014-03-01

    Cattle deaths in two contemporaneous incidents were attributed to acute intoxication with Persicaria lapathifolia and P. orientalis when the plants were under heat and moisture stress. To our knowledge this is the first confirmed report of acute, fatal hepatic necrosis associated with ingestion of these plants. PMID:24571339

  20. Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group.

    PubMed

    Lewis, J; Salem, M M; Chertow, G M; Weisberg, L S; McGrew, F; Marbury, T C; Allgren, R L

    2000-10-01

    Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality. PMID:11007679

  1. The Oncogenic MicroRNA miR-21 Promotes Regulated Necrosis in Mice

    PubMed Central

    Ma, Xiaodong; Conklin, Daniel J.; Li, Fenge; Dai, Zhongping; Hua, Xiang; Li, Yan; Xu-Monette, Zijun Y.; Young, Ken H.; Xiong, Wei; Wysoczynski, Marcin; Sithu, Srinivas D.; Srivastava, Sanjay; Bhatnagar, Aruni; Li, Yong

    2015-01-01

    MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis remains unknown. miR-21 is overexpressed in nearly all human cancer types and its role as an oncogene is suggested to largely depend on its anti-apoptotic action. Here we show that miR-21 is overexpressed in a murine model of acute pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis injury and necroptosis. miR-21 deficiency protects against caerulein- or L-arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked-nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity. miR-21 deletion is also protective in tumor necrosis factor-induced systemic inflammatory response syndrome. These data suggest that miRNAs are critical participants in necroptosis, and miR-21 enhances cellular necrosis by negatively regulating tumor suppressor genes associated with the death-receptor-mediated intrinsic apoptosis pathway and could be a therapeutic target for preventing pathologic necrosis. PMID:25990308

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

    PubMed

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

    2016-04-01

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

  3. A simple auxetic tubular structure with tuneable mechanical properties

    NASA Astrophysics Data System (ADS)

    Ren, Xin; Shen, Jianhu; Ghaedizadeh, Arash; Tian, Hongqi; Xie, Yi Min

    2016-06-01

    Auxetic materials and structures are increasingly used in various fields because of their unusual properties. Auxetic tubular structures have been fabricated and studied due to their potential to be adopted as oesophageal stents where only tensile auxetic performance is required. However, studies on compressive mechanical properties of auxetic tubular structures are limited in the current literature. In this paper, we developed a simple tubular structure which exhibits auxetic behaviour in both compression and tension. This was achieved by extending a design concept recently proposed by the authors for generating 3D metallic auxetic metamaterials. Both compressive and tensile mechanical properties of the auxetic tubular structure were investigated. It was found that the methodology for generating 3D auxetic metamaterials could be effectively used to create auxetic tubular structures as well. By properly adjusting certain parameters, the mechanical properties of the designed auxetic tubular structure could be easily tuned.

  4. Avascular necrosis of bone after allogeneic bone marrow transplantation: clinical findings, incidence and risk factors.

    PubMed

    Socié, G; Sélimi, F; Sedel, L; Frija, J; Devergie, A; Esperou Bourdeau, H; Ribaud, P; Gluckman, E

    1994-03-01

    In the present study we describe the incidence, clinical course, and management of avascular necrosis of bone following allogeneic bone marrow transplantation, and identify risk factors related to its development. All patients developing avascular necrosis of bone after allogeneic bone marrow transplantation between January 1974 and September 1992 were included in the analysis and were studied using the Hôpital Saint Louis Bone Marrow Transplant Database and hospital records. 27/727 allogeneic transplant recipients developed avascular necrosis leading to an 8.1% incidence at 5 years, by product limit estimate, ranging from 5% to 11.2%. Symptoms developed 119-1747 d (median 398 d) after transplantation. In these 27 patients a total of 52 joints were affected (mean 1.92 per patient, range 1-7). The hip joint was most often affected (69% of patients). All patients had joint pain that led to diagnosis by means of standard radiographs with or without the help of technetium-99 scans and/or magnetic resonance imaging. All but three patients received steroid therapy for acute graft-versus-host disease. Among 10 factors tested, three were shown to be significantly linked to an increased risk for developing avascular necrosis by multivariate analysis: male gender (relative risk (RR) 4.72, P = 0.002), age older than 16 (RR = 3.87, P = 0.004), and acute graft-versus-host disease requiring steroid therapy (RR = 6.30, P = 0.0002). 10 patients (37%) required joint replacement within 19 months (range 2-42) following diagnosis of avascular necrosis. In conclusion, avascular necrosis of bone is a frequent late complication of allogeneic bone marrow transplantation causing significant morbidity and requiring replacement surgery in one-third of affected patients. In this 18-year single-centre survey, older age, male gender and steroid therapy given for acute graft-versus-host disease were shown to independently increase the risk of avascular necrosis of bone. PMID:8043445

  5. Optimizing Mouse Surgery with Online Rectal Temperature Monitoring and Preoperative Heat Supply. Effects on Post-Ischemic Acute Kidney Injury

    PubMed Central

    Holderied, Alexander; Anders, Hans-Joachim

    2016-01-01

    Body temperature affects outcomes of tissue injury. We hypothesized that online body core temperature recording and selective interventions help to standardize peri-interventional temperature control and the reliability of outcomes in experimental renal ischemia reperfusion injury (IRI). We recorded core temperature in up to seven mice in parallel using a Thermes USB recorder and ret-3-iso rectal probes with three different protocols. Setup A: Heating pad during ischemia time; Setup B: Heating pad from incision to wound closure; Setup C: A ventilated heating chamber before surgery and during ischemia time with surgeries performed on a heating pad. Temperature profile recording displayed significant declines upon installing anesthesia. The profile of the baseline experimental setup A revealed that <1% of the temperature readings were within the target range of 36.5 to 38.5°C. Setup B and C increased the target range readings to 34.6 ± 28.0% and 99.3 ± 1.5%, respectively. Setup C significantly increased S3 tubular necrosis, neutrophil influx, and mRNA expression of kidney injury markers. In addition, using setup C different ischemia times generated a linear correlation with acute tubular necrosis parameters at a low variability, which further correlated with the degree of kidney atrophy 5 weeks after surgery. Changing temperature control setup A to C was equivalent to 10 minutes more ischemia time. We conclude that body temperature drops quickly in mice upon initiating anesthesia. Immediate heat supply, e.g. in a ventilated heating chamber, and online core temperature monitoring can help to standardize and optimize experimental outcomes. PMID:26890071

  6. C-reactive protein promotes acute kidney injury via Smad3-dependent inhibition of CDK2/cyclin E.

    PubMed

    Lai, Weiyan; Tang, Ying; Huang, Xiao R; Ming-Kuen Tang, Patrick; Xu, Anping; Szalai, Alexander J; Lou, Tan-Qi; Lan, Hui Y

    2016-09-01

    Acute kidney injury (AKI) is exacerbated in C-reactive protein transgenic mice but alleviated in Smad3 knockout mice. Here we used C-reactive protein transgenic/Smad3 wild-type and C-reactive protein transgenic/Smad3 knockout mice to investigate the signaling mechanisms by which C-reactive protein promotes AKI. Serum creatinine was elevated, and the extent of tubular epithelial cell necrosis following ischemia/reperfusion-induced AKI was greater in C-reactive protein transgenics but was blunted when Smad3 was deleted. Exacerbation of AKI in C-reactive protein transgenics was associated with increased TGF-β/Smad3 signaling and expression of the cyclin kinase inhibitor p27, but decreased phosphorylated CDK2 and expression of cyclin E. Concomitantly, tubular epithelial cell proliferation was arrested at the G1 phase in C-reactive protein transgenics with fewer cells entering the S-phase cell cycle as evidenced by fewer bromodeoxyuridine-positive cells. In contrast, the protection from AKI in C-reactive protein transgenic/Smad3 knockout mice was associated with decreased expression of p27 and promotion of CDK2/cyclin E-dependent G1/S transition of tubular epithelial cells. In vitro studies using tubular epithelial cells showed that C-reactive protein activates Smad3 via both TGF-β-dependent and ERK/MAPK cross talk mechanisms, Smad3 bound directly to p27, and blockade of Smad3 or the Fc receptor CD32 prevented C-reactive protein-induced p27-dependent G1 cell cycle arrest. In vivo, treatment of C-reactive protein transgenics with a Smad3 inhibitor largely improved AKI outcomes. Thus, C-reactive protein may promote AKI by impairing tubular epithelial cell regeneration via the CD32-Smad3-p27-driven inhibition of the CDK2/cyclin E complex. Targeting Smad3 may offer a new treatment approach for AKI. PMID:27470679

  7. Cerebral radiation necrosis in pediatric patients.

    PubMed

    Plimpton, S Reed; Stence, Nicholas; Hemenway, Molly; Hankinson, Todd C; Foreman, Nicholas; Liu, Arthur K

    2015-02-01

    Radiation necrosis is a well-described toxicity following radiation therapy in the brain. There is little data regarding the incidence of radiation necrosis in pediatric patients. We retrospectively reviewed our experience with 101 children with solid brain tumors. Radiation necrosis was diagnosed by examination of magnetic resonance imaging. Median follow-up for all patients was 13 months (range 3-51). Radiation necrosis occurred in 5% (5/101) of cases with a median time to onset of 1.2 months. In three of these children, the child was symptomatic, requiring management with steroids and bevacizumab. Radiation necrosis did not correlate with the administration of chemotherapy, age at treatment, or planning treatment volume. Our experience with pediatric patients treated with radiotherapy for solid brain tumor suggests that children may have an increased likelihood to develop radiation necrosis compared to adults. PMID:23647507

  8. Hyaluronan in Tubular and Interstitial Nephrocalcinosis

    NASA Astrophysics Data System (ADS)

    Verkoelen, Carl F.

    2007-04-01

    Hyaluronan (HA) is the major glycosaminoglycan (GAG) component of the renal medullary interstitium. HA is extremely large (up to 104 kDa) and composed of thousands repeating disaccharides of glucuronic acid (GlcUA) and N-acetylglucosamine (GlcNAc). HA is synthesized by hyaluronan synthases (HASs) and degraded by hyaluronidases (Hyals). The production of HA by renomedullary interstitial cells is mediated by local osmolality. When excess water needs to be excreted, increased interstitial HA seems to antagonize water reabsorption, while the opposite occurs during water conservation. Hence, papillary interstitial HA is low and Hyal high during anti-diuresis, whereas during diuresis HA is high and Hyal low. The polyanion HA plays a role in the reabsorption of hypotonic fluid by immobilizing cations (Na+) via the carboxylate (COO-) groups of GlcUA. The binding of Ca2+ to anionic HA is probably also responsible for the fact that the papilla does not become a stone despite the extremely high interstitial phosphate and oxalate. HA is also an excellent crystal binding molecule. The expression of HA at the luminal surface of renal tubular cells leads to tubular nephrocalcinosis (tubular NC). Calcium staining methods (Von Kossa, Yasue) demonstrated that crystallization inhibitors cannot avoid the occasional precipitation of calcium phosphate in the papillary interstitium (interstitial NC). These crystals are probably immediately immobilized by the gel-like HA matrix. After ulcerating through the pelvic wall the calcified matrix becomes a Randall's plaque. The attachment of calcium oxalate crystals from the primary urine to plaque may ultimately lead to the development of clinical stones in the renal calyces (nephrolithiasis).

  9. Distal Renal Tubular Acidosis and Calcium Nephrolithiasis

    NASA Astrophysics Data System (ADS)

    Moe, Orson W.; Fuster, Daniel G.; Xie, Xiao-Song

    2008-09-01

    Calcium stones are commonly encountered in patients with congenital distal renal tubular acidosis, a disease of renal acidification caused by mutations in either the vacuolar H+-ATPase (B1 or a4 subunit), anion exchanger-1, or carbonic anhydrase II. Based on the existing database, we present two hypotheses. First, heterozygotes with mutations in B1 subunit of H+-ATPase are not normal but may harbor biochemical abnormalities such as renal acidification defects, hypercalciuria, and hypocitraturia which can predispose them to kidney stone formation. Second, we propose at least two mechanisms by which mutant B1 subunit can impair H+-ATPase: defective pump assembly and defective pump activity.

  10. Advanced beaded and tubular structural panels

    NASA Technical Reports Server (NTRS)

    Musgrove, M. D.; Greene, B. E.

    1975-01-01

    A program to develop lightweight beaded and tubular structural panels is described. Applications include external surfaces, where aerodynamically acceptable, and primary structure protected by heat shields. The design configurations were optimized and selected with a computer code which iterates geometric parameters to satisfy strength, stability, and weight constraints. Methods of fabricating these configurations are discussed. Nondestructive testing produced extensive combined compression, shear, and bending test data on local buckling specimens and large panels. The optimized design concepts offer 25 to 30% weight savings compared to conventional stiffened sheet construction.

  11. Tubular solid oxide fuel cell development program

    SciTech Connect

    1995-08-01

    This paper presents an overview of the Westinghouse Solid Oxide Fuel Cell (SOFC) development activities and current program status. The Westinghouse goal is to develop a cost effective cell that can operate for 50,000 to 100,000 hours. Progress toward this goal will be discussed and test results presented for multiple single cell tests which have now successfully exceeded 56,000 hours of continuous power operation at temperature. Results of development efforts to reduce cost and increase power output of tubular SOFCs are described.

  12. How tubular epithelial cells dictate the rate of renal fibrogenesis?

    PubMed Central

    Louis, Kevin; Hertig, Alexandre

    2015-01-01

    The main threat to a kidney injury, whatever its cause and regardless of whether it is acute or chronic, is the initiation of a process of renal fibrogenesis, since fibrosis can auto-perpetuate and is of high prognostic significance in individual patients. In the clinic, a decrease in glomerular filtration rate correlates better with tubulointerstitial damage than with glomerular injury. Accumulation of the extracellular matrix should not be isolated from other significant cellular changes occurring in the kidney, such as infiltration by inflammatory cells, proliferation of myofibroblasts, obliteration of peritubular capillaries and atrophy of tubules. The aim of this review is to focus on tubular epithelial cells (TEC), which, necessarily involved in the repair process, eventually contribute to accelerating fibrogenesis. In the context of injury, TEC rapidly exhibit phenotypic and functional changes that recall their mesenchymal origin, and produce several growth factors known to activate myofibroblasts. Because they are high-demanding energy cells, TEC will subsequently suffer from the local hypoxia that progressively arises in a microenvironment where the matrix increases and capillaries become rarified. The combination of hypoxia and metabolic acidosis may induce a vicious cycle of sustained inflammation, at the center of which TEC dictate the rate of renal fibrogenesis. PMID:26167460

  13. Acute Oxalate Nephropathy following Ingestion of Averrhoa bilimbi Juice.

    PubMed

    Nair, Sreeja; George, Jacob; Kumar, Sajeev; Gracious, Noble

    2014-01-01

    Plant toxins are known to cause acute kidney injury in tropical countries. We report two cases of acute kidney injury with tubular oxalate deposition following ingestion of Averrhoa bilimbi fruit juice. Both patients had complete renal recovery though one required dialytic support. PMID:24995136

  14. Acute Oxalate Nephropathy following Ingestion of Averrhoa bilimbi Juice

    PubMed Central

    George, Jacob; Kumar, Sajeev; Gracious, Noble

    2014-01-01

    Plant toxins are known to cause acute kidney injury in tropical countries. We report two cases of acute kidney injury with tubular oxalate deposition following ingestion of Averrhoa bilimbi fruit juice. Both patients had complete renal recovery though one required dialytic support. PMID:24995136

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

    PubMed Central

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

    2011-01-01

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

  16. Cardiorenal Syndrome Type 5: In Vitro Cytotoxicity Effects on Renal Tubular Cells and Inflammatory Profile

    PubMed Central

    Brocca, Alessandra; Virzì, Grazia Maria; Pasqualin, Chiara; Pastori, Silvia; Marcante, Stefano; de Cal, Massimo; Ronco, Claudio

    2015-01-01

    Background. Cardiorenal Syndrome Type 5 (CRS Type 5) reflects concomitant cardiac and renal dysfunctions in the setting of a wide spectrum of systemic disorders. Our aim was to study in vitro effects of CRS Type 5 plasma on renal tubular cells (RTCs), in terms of cellular death and the characterization of inflammatory plasma profile in these patients. Material and Methods. We enrolled 11 CRS Type 5 patients from ICU and 16 healthy controls. Plasma from patients and controls was incubated with renal tubular cells (RTCs) and cell death was evaluated. Plasma cytokines were detected. Results. RTCs incubated with CRS Type 5 plasma showed significantly higher apoptosis and necrosis with respect to controls. Plasma cytokine profile of CRS Type 5 patients was significantly different from controls: we observed the production of pro- and anti-inflammatory mediators in these patients. Caspase-3, caspase-8, and caspase-9 were activated in cells treated with CRS Type 5 plasma compared to controls. Conclusions. Our results underline the cytotoxic effect of CRS Type 5 mediators on RTC viability, probably due to the activation of both intrinsic and extrinsic pathways of apoptosis and to the deregulation of cytokine release. The consequence may be the damage of distant organs which lead to the worsening of condition of patients. PMID:26266085

  17. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    SciTech Connect

    Huang, J.-S. Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-12-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27{sup Kip1}, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells.

  18. Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease.

    PubMed

    Bale, P M; Kan, A E; Dorney, S F

    1994-01-01

    We report the necropsy findings for three infants with the unusual combination of proximal renal tubular dysgenesis and severe congenital liver disease with excessive iron in several organs resembling neonatal hemochromatosis. Two of the infants were caucasian siblings and one was an Australian aborigine. One died in utero at 35 weeks of gestation and two died at 7 days. The liveborn infants presented with anuria and liver failure. The livers all showed marked loss of hepatocytes and replacement by pseudotubules in the collapsed lobules. The liveborn infants also showed giant cell transformation of hepatocytes, small regenerative nodules, cholestasis, and normal bile ducts. Absence of proximal renal convolutions was confirmed by epithelial membrane antigen positivity in nearly all tubules. In each family there was another sibling with congenital liver disease, fatal in one case, but no renal tubular dysgenesis. No infection or metabolic disease was uncovered in any of our patients, and the cause of the hepatocyte destruction was not determined. The combination in three infants of two rare congenital diseases could be genetic or acquired in utero from the same etiological agent. Alternatively, the absence of proximal convolutions could be secondary to hypoperfusion, perhaps because of shock due to extensive necrosis of hepatocytes. PMID:8066004

  19. Does hypokalemia contribute to acute kidney injury in chronic laxative abuse?

    PubMed

    Lee, Eun-Young; Yoon, Hyaejin; Yi, Joo-Hark; Jung, Woon-Yong; Han, Sang-Woong; Kim, Ho-Jung

    2015-06-01

    Prolonged hypokalemia from chronic laxative abuse is recognized as the cause of chronic tubulointerstitial disease, known as "hypokalemic nephropathy," but it is not clear whether it contributes to acute kidney injury (AKI). A 42-year-old woman with a history of chronic kidney disease as a result of chronic laxative abuse from a purging type of anorexia nervosa (AN-P), developed an anuric AKI requiring hemodialysis and a mild AKI 2 months later. Both episodes of AKI involved severe to moderate hypokalemia (1.2 and 2.7 mmol/L, respectively), volume depletion, and mild rhabdomyolysis. The histologic findings of the first AKI revealed the remnants of acute tubular necrosis with advanced chronic tubulointerstitial nephritis and ischemic glomerular injury. Along with these observations, the intertwined relationship among precipitants of recurrent AKI in AN-P is discussed, and then we postulate a contributory role of hypokalemia involved in the pathophysiology of the renal ischemia-induced AKI. PMID:26484031

  20. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents

    PubMed Central

    Goudah, Ayman; Abdo-El-Sooud, Khaled; Yousef, Manal A.

    2015-01-01

    Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg. PMID:27047139

  1. Does hypokalemia contribute to acute kidney injury in chronic laxative abuse?

    PubMed Central

    Lee, Eun-Young; Yoon, Hyaejin; Yi, Joo-Hark; Jung, Woon-Yong; Han, Sang-Woong; Kim, Ho-Jung

    2015-01-01

    Prolonged hypokalemia from chronic laxative abuse is recognized as the cause of chronic tubulointerstitial disease, known as “hypokalemic nephropathy,” but it is not clear whether it contributes to acute kidney injury (AKI). A 42-year-old woman with a history of chronic kidney disease as a result of chronic laxative abuse from a purging type of anorexia nervosa (AN-P), developed an anuric AKI requiring hemodialysis and a mild AKI 2 months later. Both episodes of AKI involved severe to moderate hypokalemia (1.2 and 2.7 mmol/L, respectively), volume depletion, and mild rhabdomyolysis. The histologic findings of the first AKI revealed the remnants of acute tubular necrosis with advanced chronic tubulointerstitial nephritis and ischemic glomerular injury. Along with these observations, the intertwined relationship among precipitants of recurrent AKI in AN-P is discussed, and then we postulate a contributory role of hypokalemia involved in the pathophysiology of the renal ischemia-induced AKI. PMID:26484031

  2. An unexpected cause of acute kidney injury in a patient with ANCA associated vasculitis.

    PubMed

    Choudhry, Wajid M; Nori, Uday S; Nadasdy, Tibor; Satoskar, Anjali A

    2016-05-01

    Diagnostic kidney biopsies sometimes yield clinically unsuspected diagnoses. We present a case of a 69-year-old woman with established ANCA-associated vasculitis (AAV) of 4 years duration who was in clinical remission following cytotoxic therapy and was on maintenance immunosuppression. She presented to the hospital with acute kidney injury (AKI), symptoms suggestive of a systemic vasculitis, and in addition had hypercalcemia, metabolic alkalosis. A relapse in the AAV was suspected but a diagnostic kidney biopsy showed acute tubular necrosis, patchy interstitial inflammation, and calcium phosphate deposits. It was found that the patient recently started consuming large doses of over-the-counter calcium-containing antacids and vitamin Dcontaining multivitamin supplements. Cessation of these drugs led to improvement of renal function to baseline. This case highlights several teaching points: (1) the kidney biopsy can prove to be critically important even in cases where there appears to be a more obvious clinical diagnosis, (2) AK due to calcium-alkali syndrome has characteristic histopathological changes, and (3) that the triad of hypercalcemia, metabolic alkalosis, and AKI is exclusively associated with the ingestion of excessive quantities of calcium-containing antacids. The physician should keep this in mind, and pro-actively seek pertinent medication history from the patient. A brief review of calcium-alkali syndrome is given. PMID:26932179

  3. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

    ClinicalTrials.gov

    2016-09-14

    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. [Acute pancreas necrosis with biliary peritonitis in cesarean section].

    PubMed

    Zoldos, L; Hincová, M

    1986-01-01

    The authors describe the case of a hemorrhagic pancreatitis with non-perforating biliary peritonitis. The abdomen symptomatology was hidden by the beginning contractions and due to the dystocia the delivery was finished by caesarean section. The presence of choleperitoneum required a surgical revision of the abdominal cavity which enabled to make the right diagnosis. This thesis deals with aetiology and mechanism of choleperitoneum inception during hemorrhagic pancreatitis. PMID:3788337

  5. Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience

    PubMed Central

    Kute, V. B.; Shah, P. R.; Munjappa, B. C.; Gumber, M. R.; Patel, H. V.; Jain, S. H.; Engineer, D. P.; Naresh, V. V. Sai; Vanikar, A. V.; Trivedi, H. L.

    2012-01-01

    Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. We carried out prospective study in 2010, to describe clinical characteristics, laboratory parameters, prognostic factors, and outcome in 59 (44 males, 15 females) smear-positive malaria patients with AKI. The severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) score, Multiple Organ Dysfunction Score (MODS), and Glasgow Coma Scale (GCS) scores. All patients received artesunate and hemodialysis (HD). Mean age of patients was 33.63 ± 14 years. Plasmodium falciparum malaria was seen in 76.3% (n = 45), Plasmodium vivax in 16.9% (n = 10), and mixed infection in 6.8% (n = 4) patients. Presenting clinical features were fever (100%), nausea-vomiting (85%), oliguria (61%), abdominal pain/tenderness (50.8%), and jaundice (74.5%). Mean APACHE II, SOFA, MODS, and GCS scores were 18.1 ± 3, 10.16 ± 3.09, 9.71 ± 2.69, and 14.15 ± 1.67, respectively, all were higher among patients who died than among those who survived. APACHE II ≥20, SOFA and MODS scores ≥12 were associated with higher mortality (P < 0.05). 34% patients received blood component transfusion and exchange transfusion was done in 15%. Mean number of HD sessions required was 4.59 ± 3.03. Renal biopsies were performed in five patients (three with patchy cortical necrosis and two with acute tubular necrosis). 81.3% of patients had complete renal recovery and 11.8% succumbed to malaria. Prompt diagnosis, timely HD, and supportive therapy were associated with improved survival and recovery of kidney functions in malarial with AKI. Mortality was associated with higher APACHE II, SOFA, MODS, GCS scores, requirement of inotrope, and ventilator support. PMID:22279340

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

    USGS Publications Warehouse

    Gosting, L.; Gould, R.W.

    1981-01-01

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

  7. 75 FR 3248 - Certain Oil Country Tubular Goods From China

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... the notice in the Federal Register of September 30, 2009 (74 FR 50242). The hearing was held in... COMMISSION Certain Oil Country Tubular Goods From China Determination On the basis of the record \\1... oil country tubular goods (``OCTG''), primarily provided for in subheadings 7304.29, 7305.20, and...

  8. Inductor Hardening for Magnetic-Pulse Treatment of Tubular Parts

    NASA Astrophysics Data System (ADS)

    Kurlaeyv, N. V.; Bobin, K. N.; Ryngach, N. A.; Rakhmyanov, A. Kh.

    2016-04-01

    This paper focuses on the issues of modernization of standardized inductor construction for crimping tubular parts by the pulse electromagnetic field with the aim of increasing reliability of technique and its durability. There is given the description of the pilot model of the composite inductor for crimping tubular parts, as well as the results obtained during its test operation.

  9. Renal tubular acidosis due to the milk-alkali syndrome.

    PubMed

    Rochman, J; Better, O S; Winaver, J; Chaimowitz, C; Barzilai, A; Jacobs, R

    1977-06-01

    A 60-year-old man with a history of excessive ingestion of calcium carbonate presented with azotemia, hypercalcemia and hyperphosphatemia. His acid-base status was initially normal. Following the cessation of calcium carbonate treatment, the hypercalcemia and azotemia disappeared, and the patient was found to be in metabolic acidosis with blunted acid excretion and a urine pH of 6.1. Kidney biopsy showed focal tubular calcification; the tubular damage was apparently caused by hypercalcemia and had resulted in renal tubular acidosis. During the three months of observation since that time there has been a tendecy for spontaneous remission of the renal tubular acidosis. Impaired renal hydrogen ion excretion prevented the development of metabolic alkalosis despite ingestion of alkali initially, and was later responsible for the metabolic acidosis. Renal tubular acidosis occurring as a sequel to the milk-alkali syndrome may aggravate the danger of nephrocalcinosis in this syndrome. PMID:885714

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  11. [Acute myocarditis].

    PubMed

    Combes, Alain

    2012-06-01

    Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent-onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option. PMID:22515999

  12. [Acute myocarditis].

    PubMed

    Combes, Alain

    2013-05-01

    Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option. PMID:23789482

  13. Renal tubular secretion of glutathione (GSH)

    SciTech Connect

    Scott, R.D.; Curthoys, N.P.

    1986-05-01

    The rapid turnover of renal GSH may require its secretion into the tubular lumen. Renal clearance of plasma GSH was measured in rats anesthetized with Inactin and infused with (/sup 3/H)inulin. Renal ..gamma..-glutamyltranspeptidase (..gamma..GT) was then inactivated (> 97%) by infusion of acivicin and samples were collected for 6-7 h. By 4.5 h arterial and urinary GSH increased from 5..mu..M and 1.3 n mol/h to 23 ..mu..M and 2400-7000 nmol/h, respectively. The ratio of urinary GSH to filtered load increased from < 0.01 to 0.7-2.6. When renal GSH was decreased to 30% of normal by pretreating rats with buthionine sulfoximine (BSO), the subsequent inactivation of ..gamma..GT caused only a slight increase in arterial GSH and urinary GSH increased to only 400-600 nmol/h (60-70% of filtered load). The amount of GSH filtered by the kidney was reduced by initially treating a rat with acivicin and 3 h later infusing purified ..gamma..GT (0.2 mg/h) to degrade plasma GSH. Just before infusion of ..gamma..GT, arterial GSH was 23 ..mu..M and urinary GSH was equal to 90% of the filtered load. At 1 h after infusion of ..gamma..GT, arterial GSH decreased to 0.3 ..mu..M, whereas urinary GSH remained elevated (1200-1800 nmol/h) and now equalled 10-20 times the filtered load. When similar experiments were carried out in BSO treated rats, maximal urinary GSH was reduced to 200 nmol/h, a value that was still 10 times the filtered load. Therefore, secreted GSH constitutes a significant portion of the GSH that is normally catabolized within the tubular lumen.

  14. Tubular optical microcavities of indefinite medium for sensitive liquid refractometers.

    PubMed

    Tang, Shiwei; Fang, Yangfu; Liu, Zhaowei; Zhou, Lei; Mei, Yongfeng

    2016-01-01

    Optical microcavities enable circulated light to intensively interact with a detecting liquid, thus promising high sensitivity in fluidic refractometers. Based on Mie scattering theory, we propose a tubular metamaterial device for liquid sensing, which utilizes anisotropic metamaterials with hyperbolic dispersion called indefinite media (IM). Besides traditional whispering gallery modes (WGMs), such tubular cavities can support surface plasmon polariton (SPP) WGMs, enabling high sensitivity liquid detection. Three configurations of such metamaterial tubes for sensing are discussed: tube-in-liquid, hollow-tube-in-liquid and liquid-in-tube; these are analyzed using numerical formulas and compared with dielectric and metal materials. Compared with traditional dielectric media (DM), the IM tubular cavity exhibits a higher sensitivity (S), which is close to that of a metal tubular cavity. However, compared with metal media, such an IM cavity can achieve higher quality (Q) factors similar to the DM tubular cavity. Therefore, the IM tubular cavity can offer the highest figures of merit (QS) for the sensing performance among the three types of materials. Our results suggest a novel tubular optofluidic device based on metamaterials, which could be useful for liquid refractometers. PMID:26605851

  15. [Tubular involvement in glomerular diseases of the kidney (author's transl)].

    PubMed

    Lubee, G; Balzar, E

    1977-01-21

    An attempt is made in this study to provide an answer to the question whether glomerular diseases are accompanied by tubular disorders. The urinary lysozyme activity was determined by means of a turbidimetric assay method in 10 healthy children as controls, 10 patients with glomerulonephritis, 8 patients with Alport's syndrome (hereditary glomerulonephritis with deafness) and 12 children with idiopathic nephrotic syndrome. In most of the cases a significant increase in urinary lysozyme excretion, indicative of tubular damage, was found and this finding correlates well with the tubular morphology of the patients. PMID:320767

  16. Experimental Papillary Necrosis of the Kidney

    PubMed Central

    Wyllie, R. G.; Hill, G. S.; Murray, G.; Ramsden, P. W.; Heptinstall, R. H.

    1972-01-01

    Reserpine is able to exert a pronounced inhibitory effect on the development of papillary necrosis following the administration of bromoethylamine hydrobromide to the rat. This inhibitory effect has been observed using light microscopy, histochemistry, indigo carmine excretion and urine output. These observations suggest that vasoconstriction may play a significant role in the pathogenesis of papillary necrosis, but the evidence for this is incomplete. ImagesFig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:4114974

  17. [Palatal necrosis in children. Case report].

    PubMed

    Sancho, M A; Parri, F J; Raigosa, J M; Lerena, J; Cacéres, F; Muñoz, M E

    2006-04-01

    Palate necrosis as a consequence of palate infection it's an exceptional condition about there's not too much references at literature. We present a case of a 6 months old child who present a palatal necrosis after a supurative medial otitis that involved hard and soft palate, with positive culture for Pseudomona aeruginosa causing a almost complete absence of the palate that simulate a bilateral palatal cleft. PMID:16846136

  18. Imaging Tumor Necrosis with Ferumoxytol

    PubMed Central

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

    2015-01-01

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

  19. Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

    PubMed

    Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

    2016-03-01

    Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. PMID:26616141

  20. Recent advances in the understanding of acute kidney injury

    PubMed Central

    Tögel, Florian

    2014-01-01

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

  1. Genetics Home Reference: renal tubular acidosis with deafness

    MedlinePlus

    ... a disorder characterized by kidney (renal) problems and hearing loss. The kidneys normally filter fluid and waste products ... In people with renal tubular acidosis with deafness , hearing loss caused by changes in the inner ear (sensorineural ...

  2. Autophagy and Tubular Cell Death in the Kidney.

    PubMed

    Havasi, Andrea; Dong, Zheng

    2016-05-01

    Many common renal insults such as ischemia and toxic injury primarily target the tubular epithelial cells, especially the highly metabolically active proximal tubular segment. Tubular epithelial cells are particularly dependent on autophagy to maintain homeostasis and respond to stressors. The pattern of autophagy in the kidney has a unique spatial and chronologic signature. Recent evidence has shown that there is complex cross-talk between autophagy and various cell death pathways. This review specifically discusses the interplay between autophagy and cell death in the renal tubular epithelia. It is imperative to review this topic because recent discoveries have improved our mechanistic understanding of the autophagic process and have highlighted its broad clinical applications, making autophagy a major target for drug development. PMID:27339383

  3. Atypical presentation of distal renal tubular acidosis in two siblings.

    PubMed

    Tasic, Velibor; Korneti, Petar; Gucev, Zoran; Hoppe, Bernd; Blau, Nenad; Cheong, Hae Il

    2008-07-01

    Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy. PMID:18386070

  4. Numerical Observation of a Tubular Phase in Anisotropic Membranes

    SciTech Connect

    Bowick, M.; Falcioni, M.; Thorleifsson, G.

    1997-08-01

    We provide the first numerical evidence for the existence of a tubular phase, predicted by Radzihovsky and Toner (RT), for anisotropic tethered membranes without self-avoidance. Incorporating anisotropy into the bending rigidity of a simple model of a tethered membrane with free boundary conditions, we show that the model indeed has two phase transitions corresponding to the flat-to-tubular and tubular-to-crumpled transitions. For the tubular phase we measure the Flory exponent {nu}{sub F} and the roughness exponent {zeta} . We find {nu}{sub F}=0.305(14) and {zeta}=0.895(60) , which are in reasonable agreement with the theoretical predictions of RT; {nu}{sub F}=1/4 and {zeta}=1 . {copyright} {ital 1997} {ital The American Physical Society}

  5. Distal Renal Tubular Acidosis in Infancy: A Bicarbonate Wasting State

    ERIC Educational Resources Information Center

    Rodriguez-Soriano, J.; And Others

    1975-01-01

    Studied were three unrelated infants with distal renal tubular acidosis (a condition characterized by an inability to acidify the urine to minimal pH levels resulting in the loss of bicarbonates). (DB)

  6. Radially composite piezoelectric ceramic tubular transducer in radial vibration.

    PubMed

    Shuyu, Lin; Shuaijun, Wang

    2011-11-01

    The radially composite piezoelectric tubular transducer is studied. It is composed of radially poled piezoelectric and a long metal tube. The electro-mechanical equivalent circuit of the radially poled piezoelectric and metal tube in radial vibration is obtained. Based on the force and velocity boundary conditions, the six-port electro-mechanical equivalent circuit for the composite tubular transducer is given and the resonance/anti-resonance frequency equations are obtained. The relationship between the resonance frequency and the dimensions is analyzed. Numerically simulated results obtained by the finite element method are compared with those from the analytical method. Composite piezoelectric tubular transducers are designed and manufactured. The resonance/anti-resonance frequencies are measured, and it is shown that the theoretical results are in good agreement with the simulated and experimental results. It is expected that radially composite piezoelectric tubular transducers can be used as high-power ultrasonic radiators in ultrasonic applications, such as ultrasonic liquid processing. PMID:22083782

  7. Tubular hydrogen permeable metal foil membrane and method of fabrication

    DOEpatents

    Paglieri, Stephen N.; Birdsell, Stephen A.; Barbero, Robert S.; Snow, Ronny C.; Smith, Frank M.

    2006-04-04

    A tubular hydrogen permeable metal membrane and fabrication process comprises obtaining a metal alloy foil having two surfaces, coating the surfaces with a metal or metal alloy catalytic layer to produce a hydrogen permeable metal membrane, sizing the membrane into a sheet with two long edges, wrapping the membrane around an elongated expandable rod with the two long edges aligned and overlapping to facilitate welding of the two together, placing the foil wrapped rod into a surrounding fixture housing with the two aligned and overlapping foil edges accessible through an elongated aperture in the surrounding fixture housing, expanding the elongated expandable rod within the surrounding fixture housing to tighten the foil about the expanded rod, welding the two long overlapping foil edges to one another generating a tubular membrane, and removing the tubular membrane from within the surrounding fixture housing and the expandable rod from with the tubular membrane.

  8. Development of an alternating flat to tubular Kevlar parachute tape

    SciTech Connect

    Ericksen, R.H.; Koch, R.

    1989-01-01

    An alternating flat to tubular Kevlar tape was developed to replace braided suspension lines and woven tape radials on the new crew escape module parachute system for the F-111 aircraft. Weaves were developed which had high strength efficiency and low weight throughout the flat, tubular, and transition sections. A tubular section strength of 535 lbs at a weight of 0.044 oz/yd was achieved. This reduces suspension line weight by 8% compared with that of the most efficient braid which has a strength of 470 lbs and weighs 0.048 oz/yd. Length measuring procedures for production control and inspection were developed. Using these procedures it was possible to produce alternating weave fabric with less than 1% variation in length in the tubular sections. 3 refs., 4 figs., 3 tabs.

  9. Inflatable Tubular Structures Rigidized with Foams

    NASA Technical Reports Server (NTRS)

    Tinker, Michael L.; Schnell, Andrew R.

    2010-01-01

    Inflatable tubular structures that have annular cross sections rigidized with foams, and the means of erecting such structures in the field, are undergoing development. Although the development effort has focused on lightweight structural booms to be transported in compact form and deployed in outer space, the principles of design and fabrication are also potentially applicable to terrestrial structures, including components of ultralightweight aircraft, lightweight storage buildings and shelters, lightweight insulation, and sales displays. The use of foams to deploy and harden inflatable structures was first proposed as early as the 1960s, and has been investigated in recent years by NASA, the U.S. Air Force Research Laboratory, industry, and academia. In cases of deployable booms, most of the investigation in recent years has focused on solid cross sections, because they can be constructed relatively easily. However, solid-section foam-filled booms can be much too heavy for some applications. In contrast, booms with annular cross sections according to the present innovation can be tailored to obtain desired combinations of stiffness and weight through choice of diameters, wall thicknesses, and foam densities. By far the most compelling advantage afforded by this innovation is the possibility of drastically reducing weights while retaining or increasing the stiffnesses, relative to comparable booms that have solid foamfilled cross sections. A typical boom according to this innovation includes inner and outer polyimide film sleeves to contain foam that is injected between them during deployment.

  10. Tubular filamentation for laser material processing.

    PubMed

    Xie, Chen; Jukna, Vytautas; Milián, Carles; Giust, Remo; Ouadghiri-Idrissi, Ismail; Itina, Tatiana; Dudley, John M; Couairon, Arnaud; Courvoisier, Francois

    2015-01-01

    An open challenge in the important field of femtosecond laser material processing is the controlled internal structuring of dielectric materials. Although the availability of high energy high repetition rate femtosecond lasers has led to many advances in this field, writing structures within transparent dielectrics at intensities exceeding 10(13) W/cm(2) has remained difficult as it is associated with significant nonlinear spatial distortion. This letter reports the existence of a new propagation regime for femtosecond pulses at high power that overcomes this challenge, associated with the generation of a hollow uniform and intense light tube that remains propagation invariant even at intensities associated with dense plasma formation. This regime is seeded from higher order nondiffracting Bessel beams, which carry an optical vortex charge. Numerical simulations are quantitatively confirmed by experiments where a novel experimental approach allows direct imaging of the 3D fluence distribution within transparent solids. We also analyze the transitions to other propagation regimes in near and far fields. We demonstrate how the generation of plasma in this tubular geometry can lead to applications in ultrafast laser material processing in terms of single shot index writing, and discuss how it opens important perspectives for material compression and filamentation guiding in atmosphere. PMID:25753215

  11. Developments in open tubular liquid chromatography

    SciTech Connect

    Vargo, J.D.; Maskarinec, M.P.; Sepaniak, M.J.

    1984-04-01

    In this report the band broadening introduced by detection flow cell use in open tubular liquid chromatography (OTLC) was thoroughly examined. Serious loss of chromatographic efficiency and resolution can occur if the flow cell size is not properly matched with the ID of the column. Detection in a flow cell was shown to be more sensitive than on-column detection, but at the expense of some loss in chromatographic efficiency. The use of fluorescence as a sensitive detection method for OTLC was presented in detail. The application of the laser as excitation source was developed. The laser based fluorometric system proved to be a sensitive detection method which was relatively easy to operate and optimize. This system allowed on-column detection to be used. An electro-etching procedure for borosilicate glass developed by Jorgenson and Guthrie was modified such that longer columns could be effectively etched. It was shown that the acidification of the etched glass surface significantly increased capacity factor (k') values for bonded phase columns. Soda-lime glass was shown to be the most suitable material for column fabrication. Complex natural samples were separated by OTLC. The alkyl phenol compounds in a coal-derived liquid were separated and tentatively identified. A chromatographic separation of a derivatized sample of coal oil bases is also presented.

  12. Cytocompatibility of a silk fibroin tubular scaffold.

    PubMed

    Wang, Jiannan; Wei, Yali; Yi, Honggen; Liu, Zhiwu; Sun, Dan; Zhao, Huanrong

    2014-01-01

    Regenerated silk fibroin (SF) materials are increasingly used for tissue engineering applications. In order to explore the feasibility of a novel biomimetic silk fibroin tubular scaffold (SFTS) crosslinked by poly(ethylene glycol) diglycidyl ether (PEG-DE), biocompatibility with cells was evaluated. The novel biomimetic design of the SFTS consisted of three distinct layers: a regenerated SF intima, a silk braided media and a regenerated SF adventitia. The SFTS exhibited even silk fibroin penetration throughout the braid, forming a porous layered tube with superior mechanical, permeable and cell adhesion properties that are beneficial to vascular regeneration. Cytotoxicity and cell compatibility were tested on L929 cells and human umbilical vein endothelial cells (EA.hy926). DNA content analysis, scanning electron and confocal microscopies and MTT assay showed no inhibitory effects on DNA replication. Cell morphology, viability and proliferation were good for L929 cells, and satisfactory for EA.hy926 cells. Furthermore, the suture retention strength of the SFTS was about 23N and the Young's modulus was 0.2-0.3MPa. Collectively, these data demonstrate that PEG-DE crosslinked SFTS possesses the appropriate cytocompatibility and mechanical properties for use as vascular scaffolds as an alternative to vascular autografts. PMID:24268279

  13. Renal tubular vasopressin receptors downregulated by dehydration

    SciTech Connect

    Steiner, M.; Phillips, M.I. )

    1988-03-01

    Receptors for arginine vasopressin (AVP) were characterized in tubular epithelial basolateral membranes (BL membranes) prepared from the kidneys of male Spraque-Dawley rats. Association of ({sup 3}H)AVP was rapid, reversible, and specific. Saturation studies revealed a single class of saturable binding sites with a maximal binding (B{sub max}) of 184 {plus minus} 15 fmol/mg protein. The V{sub 2} receptor antagonist was more than 3,700 times as effective in displacing ({sup 3}H)AVP than was the V{sub 1} antagonist. To investigate the physiological regulation of vasopressin receptors, the effects of elevated levels of circulating AVP on receptor characteristics were studied. Seventy-two-hour water deprivation significantly elevated plasma osmolality and caused an 11.5-fold increase in plasma (AVP). Scatchard analysis revealed a 38% decreased in the number of AVP receptors on the BL membranes from dehydrated animals. The high-affinity binding sites on the BL membranes fit the pharmacological profile for adenylate cyclase-linked vasopressin receptors (V{sub 2}), which mediate the antidiuretic action of the hormone. The authors conclude that physiologically elevated levels of AVP can downregulate vasopressin receptors in the kidney.

  14. Tubular filamentation for laser material processing

    PubMed Central

    Xie, Chen; Jukna, Vytautas; Milián, Carles; Giust, Remo; Ouadghiri-Idrissi, Ismail; Itina, Tatiana; Dudley, John M.; Couairon, Arnaud; Courvoisier, Francois

    2015-01-01

    An open challenge in the important field of femtosecond laser material processing is the controlled internal structuring of dielectric materials. Although the availability of high energy high repetition rate femtosecond lasers has led to many advances in this field, writing structures within transparent dielectrics at intensities exceeding 1013 W/cm2 has remained difficult as it is associated with significant nonlinear spatial distortion. This letter reports the existence of a new propagation regime for femtosecond pulses at high power that overcomes this challenge, associated with the generation of a hollow uniform and intense light tube that remains propagation invariant even at intensities associated with dense plasma formation. This regime is seeded from higher order nondiffracting Bessel beams, which carry an optical vortex charge. Numerical simulations are quantitatively confirmed by experiments where a novel experimental approach allows direct imaging of the 3D fluence distribution within transparent solids. We also analyze the transitions to other propagation regimes in near and far fields. We demonstrate how the generation of plasma in this tubular geometry can lead to applications in ultrafast laser material processing in terms of single shot index writing, and discuss how it opens important perspectives for material compression and filamentation guiding in atmosphere. PMID:25753215

  15. Cadmium, metallothionein and renal tubular toxicity.

    PubMed

    Nordberg, M; Jin, T; Nordberg, G F

    1992-01-01

    Cadmium-induced nephrotoxicity develops at cadmium concentrations in the renal cortex of 10-300 micrograms/g wet weight. The actual concentration at which it develops depends on a number of factors, e.g., exposure route, chemical species of cadmium administered, rate of administration and simultaneous exposure to other metals. The role of these factors can be explained by a mechanism of cadmium nephrotoxicity in which both extracellular and intracellular metallothionein binding play an essential role. In reindeer used for human food, cadmium was shown to be bound to metallothionein-like proteins. If cadmium bound to such proteins enters the blood plasma via the gastrointestinal tract, this is of special toxicological significance. Metallothionein-bound cadmium in the plasma of experimental animals is efficiently transported to the kidney. Tubular dysfunction in the kidney following a normally tubulotoxic dose of cadmium bound to metallothionein was prevented by preinduction of metallothionein synthesis by small non-toxic doses of cadmium. PMID:1303954

  16. Pressure driven flow in porous tubular membranes

    NASA Astrophysics Data System (ADS)

    Tilton, Nils; Martinand, Denis; Serre, Eric; Lueptow, Richard

    2011-11-01

    We consider the steady laminar flow of a Newtonian incompressible fluid in a porous tubular membrane with pressure-driven transmembrane flow. Due to its fundamental importance to membrane filtration systems, this flow has been studied extensively both analytically and numerically, yet a robust analytic solution has not been found. The problem is challenging due to the coupling between the transmembrane pressure and velocity with the simultaneous coupling between the axial pressure gradient and the axial velocity. We present a robust analytical solution which incorporates Darcy's law on the membrane surface. The solution is in the form of an asymptotic expansion about a small parameter related to the membrane permeability. We verify the analytical solution with comparison to 2-D spectral direct numerical simulations of ultrafiltration and microfiltration systems with typical operating conditions, as well as extreme cases of cross-flow reversal and axial flow exhaustion. In all cases, the agreement between the analytical and numerical results is excellent. Finally, we use the analytical and numerical results to provide guidelines about when common simplifying assumptions about the permeate flow may be made. Specifically, the assumptions of a parabolic axial velocity profile and uniform transmembrane velocity are valid only for small permeabilities.

  17. Electrolyte composition of renal tubular cells in gentamicin nephrotoxicity

    SciTech Connect

    Matsuda, O.; Beck, F.X.; Doerge, A.T.; Thurau, K.

    1988-06-01

    The effect of long-term gentamicin administration on sodium, potassium, chloride and phosphorus concentrations was studied in individual rat renal tubular cells using electron microprobe analysis. Histological damage was apparent only in proximal tubular cells. The extent of damage was only mild after 7 days of gentamicin administration (60 mg/kg body wt/day) but much more pronounced after 10 days. GFR showed a progressive decline during gentamicin treatment. In non-necrotic proximal tubular cells, sodium was increased from 14.6 +/- 0.3 (mean +/- SEM) in controls to 20.6 +/- 0.4 after 7 and 22.0 +/- 0.8 mmol/kg wet wt after 10 days of gentamicin administration. Chloride concentration was higher only after 10 days (20.6 +/- 0.6 vs. 17.3 +/- 0.2 mmol/kg wet wt). Both cell potassium and phosphorus concentrations were diminished by 6 and 15, and by 8 and 25 mmol/kg wet wt after 7 and 10 days of treatment, respectively. In contrast, no major alterations in distal tubular cell electrolyte concentrations could be observed after either 7 or 10 days of gentamicin administration. As in proximal tubular cells, distal tubular cell phosphorus concentrations were, however, lowered by gentamicin treatment. These results clearly indicate that gentamicin exerts its main effect on proximal tubular cells. Decreased potassium and increased sodium and chloride concentrations were observed in proximal tubular cells exhibiting only mild histological damage prior to the onset of advanced tissue injury. Necrotic cells, on the other hand, showed widely variable intracellular electrolyte concentration patterns.

  18. Reduction in toxicity of coking wastewater to aquatic organisms by vertical tubular biological reactor.

    PubMed

    Zhou, Siyun; Watanabe, Haruna; Wei, Chang; Wang, Dongzhou; Zhou, Jiti; Tatarazako, Norihisa; Masunaga, Shigeki; Zhang, Ying

    2015-05-01

    We conducted a battery of toxicity tests using photo bacterium, algae, crustacean and fish to evaluate acute toxicity profile of coking wastewater, and to evaluate the performance of a novel wastewater treatment process, vertical tubular biological reactor (VTBR), in the removal of toxicity and certain chemical pollutants. A laboratory scale VTBR system was set up to treat industrial coking wastewater, and investigated both chemicals removal efficiency and acute bio-toxicity to aquatic organisms. The results showed that chemical oxygen demand (COD) and phenol reductions by VTBR were approximately 93% and 100%, respectively. VTBR also reduced the acute toxicity of coking wastewater significantly: Toxicity Unit (TU) decreased from 21.2 to 0.4 for Photobacterium phosphoreum, from 9.5 to 0.6 for Isochrysis galbana, from 31.9 to 1.3 for Daphnia magna, and from 30.0 to nearly 0 for Danio rerio. VTBR is an efficient treatment method for the removal of chemical pollutants and acute bio-toxicity from coking wastewater. PMID:25706086

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

    PubMed

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

    2012-05-01

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

  20. Management of severe acute pancreatitis.

    PubMed

    Doctor, Nilesh; Agarwal, Pravin; Gandhi, Vidhyachandra

    2012-02-01

    Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis. Severity of acute pancreatitis is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis. Risk factors independently determining the outcome of SAP are early multiorgan failure (MOF), infection of necrosis, and extended necrosis (>50%). Morbidity of SAP is biphasic, in the first week it is strongly related to systemic inflammatory response syndrome while, sepsis due to infected pancreatic necrosis leading to MOF syndrome occurs in the later course after the first week. Contrast-enhanced computed tomography provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or are at risk for developing a severe disease require early intensive care treatment. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis are candidates for intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased to below 20% in high-volume centers. PMID:23372306

  1. Straightening tubular flow for side-by-side visualization.

    PubMed

    Angelelli, Paolo; Hauser, Helwig

    2011-12-01

    Flows through tubular structures are common in many fields, including blood flow in medicine and tubular fluid flows in engineering. The analysis of such flows is often done with a strong reference to the main flow direction along the tubular boundary. In this paper we present an approach for straightening the visualization of tubular flow. By aligning the main reference direction of the flow, i.e., the center line of the bounding tubular structure, with one axis of the screen, we are able to natively juxtapose (1.) different visualizations of the same flow, either utilizing different flow visualization techniques, or by varying parameters of a chosen approach such as the choice of seeding locations for integration-based flow visualization, (2.) the different time steps of a time-dependent flow, (3.) different projections around the center line , and (4.) quantitative flow visualizations in immediate spatial relation to the more qualitative classical flow visualization. We describe how to utilize this approach for an informative interactive visual analysis. We demonstrate the potential of our approach by visualizing two datasets from two different fields: an arterial blood flow measurement and a tubular gas flow simulation from the automotive industry. PMID:22034324

  2. Enhanced cadmium-induced testicular necrosis and renal proximal tubule damage caused by gene-dose increase in a Slc39a8-transgenic mouse line.

    PubMed

    Wang, Bin; Schneider, Scott N; Dragin, Nadine; Girijashanker, Kuppuswami; Dalton, Timothy P; He, Lei; Miller, Marian L; Stringer, Keith F; Soleimani, Manoocher; Richardson, Douglas D; Nebert, Daniel W

    2007-04-01

    Resistance to cadmium (Cd)-induced testicular necrosis is an autosomal recessive trait defined as the Cdm locus. Using positional cloning, we previously identified the Slc39a8 (encoding an apical-surface ZIP8 transporter protein) as the gene most likely responsible for the phenotype. In situ hybridization revealed that endothelial cells of the testis vasculature express high ZIP8 levels in two sensitive inbred mouse strains and negligible amounts in two resistant strains. In the present study, we isolated a 168.7-kb bacterial artificial chromosome (BAC), carrying only the Slc39a8 gene, from a Cd-sensitive 129/SvJ BAC library and generated BAC-transgenic mice. The BTZIP8-3 line, having three copies of the 129/SvJ Slc39a8 gene inserted into the Cd-resistant C57BL/6J genome (having its normal two copies of the Slc39a8 gene), showed tissue-specific ZIP8 mRNA expression similar to wild-type mice, mainly in lung, testis, and kidney. The approximately 2.5-fold greater expression paralleled the fact that the BTZIP8-3 line has five copies, whereas wild-type mice have two copies, of the Slc39a8 gene. The ZIP8 mRNA and protein localized especially to endothelial cells of the testis vasculature in BTZIP8-3 mice. Cd treatment reversed Cd resistance (seen in nontransgenic littermates) to Cd sensitivity in BTZIP8-3 mice; reversal of the testicular necrosis phenotype confirms that Slc39a8 is unequivocally the Cdm locus. ZIP8 also localized specifically to the apical surface of proximal tubule cells in the BTZIP8-3 kidney. Cd treatment caused acute renal failure and signs of proximal tubular damage in the BTZIP8-3 but not nontransgenic littermates. BTZIP8-3 mice should be a useful model for studying Cd-induced disease in kidney. PMID:17108009

  3. Toxicological significance of renal Bcrp: Another potential transporter in the elimination of mercuric ions from proximal tubular cells

    SciTech Connect

    Bridges, Christy C. Zalups, Rudolfs K.; Joshee, Lucy

    2015-06-01

    Secretion of inorganic mercury (Hg{sup 2+}) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg{sup 2+} was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg{sup 2+}. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg{sup 2+}-induced nephropathy, Sprague–Dawley and Bcrp knockout (bcrp{sup −/−}) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol·kg{sup −1}), a moderately nephrotoxic (1.5 μmol·kg{sup −1}) or a significantly nephrotoxic (2.0 μmol·kg{sup −1}) dose of HgCl{sub 2}. In general, the accumulation of Hg{sup 2+} was greater in organs of bcrp{sup −/−} rats than in Sprague–Dawley rats, suggesting that Bcrp may play a role in the export of Hg{sup 2+} from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp{sup −/−} rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla, was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. - Highlights: • Bcrp may mediate transport of mercury out of proximal tubular cells. • Hg-induced nephropathy was more severe in Bcrp knockout rats. • Bcrp and Mrp2 may differ in their ability to transport Hg.

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

    PubMed Central

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

    2015-01-01

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

  5. Correlation of MRI Biomarkers with Tumor Necrosis in Hras5 Tumor Xenograft in Athymic Rats

    PubMed Central

    Bradley, Daniel P; Tessier, Jean J; Ashton, Susan E; Waterton, John C; Wilson, Zena; Worthington, Philip L; Ryan, Anderson J

    2007-01-01

    Magnetic resonance imaging (MRI) can measure the effects of therapies targeting the tumor vasculature and has demonstrated that vascular-damaging agents (VDA) induce acute vascular shutdown in tumors in human and animal models. However, at subtherapeutic doses, blood flow may recover before the induction of significant levels of necrosis. We present the relationship between changes in MRI biomarkers and tumor necrosis. Multiple MRI measurements were taken at 4.7 T in athymic rats (n = 24) bearing 1.94 ± 0.2-cm3 subcutaneous Hras5 tumors (ATCC 41000) before and 24 hours after clinically relevant doses of the VDA, ZD6126 (0–10 mg/kg, i.v.). We measured effective transverse relaxation rate (R2*), initial area under the gadolinium concentration-time curve (IAUGC60/150), equivalent enhancing fractions (EHF60/150), time constant (Ktrans), proportion of hypoperfused voxels as estimated from fit failures in Ktrans analysis, and signal intensity (SI) in T2-weighted MRI (T2W). ZD6126 treatment induced > 90% dose-dependent tumor necrosis at 10 mg/kg; correspondingly, SI changes were evident from T2W MRI. Although R2* did not correlate, other MRI biomarkers significantly correlated with necrosis at doses of ≥ 5 mg/kg ZD6126. These data on Hras5 tumors suggest that the quantification of hypoperfused voxels might provide a useful biomarker of tumor necrosis. PMID:17534443

  6. Coumadin-induced skin necrosis in a 64 year-old female despite LMWH bridging therapy

    PubMed Central

    Kumar, Mehandar; Abrina, Vanessa Mae; Chittimireddy, Sasikala

    2012-01-01

    Summary Background: Coumadin is the standard oral anticoagulant used in a variety of clinical conditions. Coumadin inhibits the vitamin-K dependent gamma-carboxylation of coagulation factors II, VII, IX, X and the anticoagulant proteins C and S. Rarely, skin necrosis occurs when the resultant initial procoagulant state in the first few days of starting coumadin leads to thrombosis and formation of blood clots tin the dermal capillaries. This in turn causes skin necrosis due to interruption in blood supply to the skin. Case Report: We are presenting the case of a 64 year-old female admitted for acute respiratory distress secondary to newly-diagnosed pulmonary embolism. The patient was started on therapeutic doses of low molecular weight heparin (LMWH) and coumadin. After 5 days of treatment, the patient started complaining of pain and numbness in both upper extremities. Overnight, this rapidly progressed to manifest hemorrhagic bullae with necrotic areas. This was immediately recognized as coumadin-induced skin necrosis. Coumadin was stopped immediately. Vitamin K was administered and local wound care was provided. Therapeutic LMWH was continued. The skin lesions began to show improvement after 3 days. Conclusions: In coumadin-induced skin necrosis, the patient initially presents with pain and erythema, followed by petechial lesions which progress to become purpuric. Hemorrhagic bullae with necrosis and eschar formation may soon develop. Once it is suspected, coumadin should be stopped and the patient should be given Vitamin K and FFP to reverse the effects of coumadin. PMID:23569516

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

    PubMed Central

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

    2015-01-01

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

  8. Beneficial Effects of Necrosis Modulator, Indole Derivative NecroX-7, on Renal Ischemia-Reperfusion Injury in Rats.

    PubMed

    Jin, S A; Kim, S K; Seo, H J; Jeong, J Y; Ahn, K T; Kim, J H; Choi, D E; Park, J H; Lee, J H; Choi, S W; Seong, I W; Kim, S H; Suh, K S; Jeong, J-O

    2016-01-01

    Renal ischemia-reperfusion injury (IRI) is involved in multiple diseases, such as kidney transplantation or contrast-induced nephropathy, and leads to acute kidney injury. However, there are no pharmacological agents available to prevent IRI. In this study, we investigated the effects of necroX-7 against renal IRI in a rat model. Seven-week-old male Sprague-Dawley rats were divided into four groups: saline-treated sham or IRI group, necroX-7-treated sham or IRI group. All animals had right nephrectomy and IRI was followed by reperfusion after clamping the left renal vessels for 35 minutes. NecroX-7 or saline was intravenously injected at 5 minutes before reperfusion. The effects of necroX-7 on IRI were evaluated using biochemical, histological, and molecular markers. The serum creatinine level was increased after IRI compared with sham. The necroX-7 significantly decreased creatinine level compared with the saline in IRI (1.36 ± 0.11 vs 2.35 ± 0.42 mg/dL; P < .05). An immunohistochemical study revealed that necroX-7 improved renal tubular injury, and attenuated 8-OHdG-positive cells (P < .001) and high-mobility group Box 1 protein (HMGB1) expression compared with saline treatment in IRI (P < .001). NecroX-7 significantly reduced monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß in IRI (necroX-7-treated IRI vs saline-treated IRI rats; 1.73 ± 0.42 vs 7.23 ± 0.54-fold for MCP-1, P < .05; 0.79 ± 0.59 vs 3.72 ± 0.37-fold for TNF-α, P < .05; 0.50 ± 0.36 vs 2.43 ± 0.41-fold for IL-1ß, P < .001). In conclusion, necroX-7 improved renal dysfunction after IRI. These effects of necroX-7 occurred with the suppression of reactive oxygen species, HMGB1, and inflammatory responses. We suggest that necroX-7 has potential therapeutic benefits in renal IRI. PMID:26915868

  9. Acute treatment with relaxin protects the kidney against ischaemia/reperfusion injury

    PubMed Central

    Collino, Massimo; Rogazzo, Mara; Pini, Alessandro; Benetti, Elisa; Rosa, Arianna Carolina; Chiazza, Fausto; Fantozzi, Roberto; Bani, Daniele; Masini, Emanuela

    2013-01-01

    Although recent preclinical and clinical studies have demonstrated that recombinant human relaxin (rhRLX) may have important therapeutic potential in acute heart failure and chronic kidney diseases, the effects of acute rhRLX administration against renal ischaemia/reperfusion (I/R) injury have never been investigated. Using a rat model of 1-hr bilateral renal artery occlusion followed by 6-hr reperfusion, we investigated the effects of rhRLX (5 μg/Kg i.v.) given both at the beginning and after 3 hrs of reperfusion. Acute rhRLX administration attenuated the functional renal injury (increase in serum urea and creatinine), glomerular dysfunction (decrease in creatinine clearance) and tubular dysfunction (increase in urinary excretion of N-acetyl-β-glucosaminidase) evoked by renal I/R. These beneficial effects were accompanied by a significant reduction in local lipid peroxidation, free radical-induced DNA damage and increase in the expression/activity of the endogenous antioxidant enzymes MnSOD and CuZnSOD superoxide dismutases (SOD). Furthermore, rhRLX administration attenuated the increase in leucocyte activation, as suggested by inhibition of myeloperoxidase activity, intercellular-adhesion-molecule-1 expression, interleukin (IL)-1β, IL-18 and tumour necrosis factor-α production as well as increase in IL-10 production. Interestingly, the reduced oxidative stress status and neutrophil activation here reported were associated with rhRLX-induced activation of endothelial nitric oxide synthase and up-regulation of inducible nitric oxide synthase, possibly secondary to activation of Akt and the extracellular signal-regulated protein kinase (ERK) 1/2, respectively. Thus, we report herein that rhRLX protects the kidney against I/R injury by a mechanism that involves changes in nitric oxide signalling pathway. PMID:24079335

  10. Cephalosporin and carbacephem nephrotoxicity. Roles of tubular cell uptake and acylating potential.

    PubMed

    Tune, B M; Hsu, C Y; Fravert, D

    1996-02-23

    Three beta-lactams, desacetylcephaloglycin, ampicillin, and loracarbef, were studied to test a hypothesis derived from retrospective analysis of previously studied cephalosporins: that beta-lactam nephrotoxicity develops in approximate proportion to tubular cell antibiotic concentrations and lactam ring reactivities. Concentrations of each beta-lactam (and insulin) in rabbit renal cortex and serum were measured at the end of 0.5-hr infusions of 100 mg antibiotic/kg body weight and 0.5 to 0.67 hr later. Total cortical AUCs (total areas under the curve of concentration and time in renal cortex) and transported cortical AUCs (total minus insulin-space beta lactam) were calculated from these measurements. Reactivities, determined by the rate constants of lactam-ring opening at pH 10, were taken from the literature. Nephrotoxicity was quantified by grades of proximal tubular cell necrosis and by serum creatinine concentrations 2 days after infusion of 100-1500 mg/kg of the antibiotics. Desacetylcephaloglycin was slightly less nephrotoxic than cephaloglycin; the AUCs reactivities, and toxicities of these two cephalosporins fit the proposed model, particularly when allowance is made for hepatic and renal deacetylation of cephaloglycin. The very low AUCs, limited reactivity, and absence of nephrotoxicity of ampicillin also fit the model. Loracarbef had a transported AUC less than three times, and reactivity one-thirtieth, those of cefaclor, respectively. Although only at 1500 mg/kg, loracarbef was significantly more nephrotic than cefaclor. If the relativity of loracarbef with its targeted bacterial proteins, which is essentially the same as that of cefaclor, is considered instead of the base hydrolysis rate constant, than loracarbef also fits the model. By the same analysis, the comparatively high in vitro stability of other carbacephems, although pharmaceutically convenient, may not limit their nephrotoxicity. PMID:8619902

  11. Structural studies of tubular discotic liquid crystals

    NASA Astrophysics Data System (ADS)

    Mindyuk, Oksana Yaroslavovna

    1999-11-01

    Discotic liquid crystals based on the rigid ring-shaped phenylacetylene macrocycle molecule (PAM) are of great interest due to their potential organization into supramolecular channels. We have used high resolution X-ray diffraction to study the structure of pure and doped PAM and to demonstrate that PAM forms a tubular columnar liquid crystal with an unexpected distortion and doubling of the underlying hexagonal lattice. We have doped PAM with different percentages of silver ions and determined that doping did not change peak positions on the powder diffraction data but significantly altered the intensity of the peaks. This implies that the silver ions were most likely intercalated within the channels formed by the PAM molecules, thus leaving the lattice parameters unaffected. We have also used grazing incidence X-ray diffraction and X-ray reflectivity to study Langmuir films of PAM. PAM adopts an "edge-on" molecular arrangement at the air-water interface. We will discuss the direct observation of the structural reorganization within macromolecular Langmuir films of disc-shaped ionophoric molecules arising from interactions with potassium and cesium ions in the subphase. The columnar order is disrupted by CsCl in the subphase and strongly enhanced by KCl in the subphase, thus effectively tailoring the structural properties of the Langmuir films for potential applications. We have also used X-ray reflectivity (XR) and grazing incidence x-ray diffraction (GID) to study Langmuir films of another macrocyclic ionophore: torand (tributyldodecahydrohexaazakekulene, "TBDK") molecules. TBDK is a rigid, triangular molecule; it has been investigated as a potential surface-active complexing agent. The system forms a stable monolayer at the air-water interface and exhibits two distinct structural phases at lower and higher pressures.

  12. Clinical profile of distal renal tubular acidosis.

    PubMed

    Jha, Ratan; Muthukrishnan, J; Shiradhonkar, Shekhar; Patro, Kiran; Harikumar, Kvs; Modi, K D

    2011-03-01

    To determine the clinical profile and progression of renal dysfunction in distal renal tubular acidosis (dRTA), we retrospectively studied 96 consecutive cases of dRTA diagnosed at our center. Patients with unexplained metabolic bone disease, short stature, hypokalemia, re-current renal stones, chronic obstructive uropathy or any primary autoimmune condition known to cause dRTA were screened. Distal RTA was diagnosed on the basis of systemic metabolic acidosis with urine pH >5.5 and positive urine anion gap. In those patients who had fasting urine pH >5.5 with normal baseline systemic pH and bicarbonate levels (incomplete RTA), acid load test with ammonium chloride was done. A cause of dRTA could be established in 53 (54%) patients. Urological defect in children (22/44) and autoimmune disease in adults (11/52) were the commonest causes. Hypokalemic paralysis, proximal muscle weakness and voiding difficulty were the common modes of presentation. Doubling of serum creatinine during the study period was noted in 13 out of 27 patients who had GFR <60 mL/min at presentation whereas in only one of the 70 with initial GFR >60 mL/min (P <0.005). In conclusion, urological disorders were the commonest cause of dRTA in children while autoimmune disorders were the commonest asso-ciation in adults. Worse baseline renal function, longer duration of disease and greater frequency of nephrolithiasis/nephrocalcinosis and urological disorders were noted in those who had wor-sening of renal dysfunction during the study period. PMID:21422623

  13. Renal Papillary Necrosis: Role of Radiology

    PubMed Central

    Pandya, Vaidehi K.

    2016-01-01

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

  14. Hyperglycemia Increases Susceptibility to Ischemic Necrosis

    PubMed Central

    Lévigne, D.; Tobalem, M.; Modarressi, A.; Pittet-Cuénod, B.

    2013-01-01

    Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.). In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia. PMID:23509730

  15. Amelioration of Acute Kidney Injury in Lipopolysaccharide-Induced Systemic Inflammatory Response Syndrome by an Aldose Reductase Inhibitor, Fidarestat

    PubMed Central

    Takahashi, Kazunori; Mizukami, Hiroki; Kamata, Kosuke; Inaba, Wataru; Kato, Noriaki; Hibi, Chihiro; Yagihashi, Soroku

    2012-01-01

    Background Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney injury is a serious complication of systemic inflammatory response syndrome and its genesis is still unclear posing a difficulty for an effective treatment. Aldose reductase (AR) inhibitor is recently found to suppress lipopolysaccharide (LPS)-induced cardiac failure and its lethality. We studied the effects of AR inhibitor on LPS-induced acute kidney injury and its mechanism. Methods Mice were injected with LPS and the effects of AR inhibitor (Fidarestat 32 mg/kg) before or after LPS injection were examined for the mortality, severity of renal failure and kidney pathology. Serum concentrations of cytokines (interleukin-1β, interleukin-6, monocyte chemotactic protein-1 and tumor necrosis factor-α) and their mRNA expressions in the lung, liver, spleen and kidney were measured. We also evaluated polyol metabolites in the kidney. Results Mortality rate within 72 hours was significantly less in LPS-injected mice treated with AR inhibitor both before (29%) and after LPS injection (40%) than untreated mice (90%). LPS-injected mice showed marked increases in blood urea nitrogen, creatinine and cytokines, and AR inhibitor treatment suppressed the changes. LPS-induced acute kidney injury was associated with vacuolar degeneration and apoptosis of renal tubular cells as well as infiltration of neutrophils and macrophages. With improvement of such pathological findings, AR inhibitor treatment suppressed the elevation of cytokine mRNA levels in multiple organs and renal sorbitol accumulation. Conclusion AR inhibitor treatment ameliorated LPS-induced acute kidney injury, resulting in the lowered mortality. PMID:22253906

  16. Distinct pathogenic effects of group B coxsackieviruses on human glomerular and tubular kidney cells.

    PubMed Central

    Conaldi, P G; Biancone, L; Bottelli, A; De Martino, A; Camussi, G; Toniolo, A

    1997-01-01

    The six group B coxsackieviruses (CVBs) are highly prevalent human pathogens that cause viremia followed by involvement of different organs. Clinical and experimental evidence suggests that CVBs can induce kidney injury, but the susceptibility of human renal cells to these viruses is unknown. By using pure cultures of human glomerular and tubular cells, we demonstrated that all CVBs are capable of productively infecting renal cells of three different histotypes. Distinct pathogenic effects were observed. Proximal tubular epithelial cells and, to a lesser extent, glomerular podocytes were highly susceptible to CVBs; in both cases, infection led to cytolysis. In contrast, glomerular mesangial cells supported the replication of the six CVBs but failed to develop overt cytopathologic changes. Mesangial cells continued to produce infectious progeny for numerous serial subcultures (i.e., more than 50 days), especially with type 1, 3, 4, and 5 viruses. In the above cells, persistent infection induced the de novo synthesis of platelet-derived growth factor A/B and enhanced the release of transforming growth factor beta1/2. These two factors are important mediators of progression from glomerular inflammation to glomerulosclerosis. CVB replication appeared also to impair the phagocytic and contractile activity of mesangial cells. Loss of these properties--which are important in glomerular physiopathology--may contribute to the development of progressive nephropathy. The results show that CVBs induce distinct effects in different types of cultured renal cells and suggest that CVB infections may be associated with both acute and progressive renal injury. PMID:9371576

  17. IGF-1 protects tubular epithelial cells during injury via activation of ERK/MAPK signaling pathway

    PubMed Central

    Wu, Zengbin; Yu, Yang; Niu, Lei; Fei, Aihua; Pan, Shuming

    2016-01-01

    Injury of renal tubular epithelial cells can induce acute renal failure and obstructive nephropathy. Previous studies have shown that administration of insulin-like growth factor-1 (IGF-1) ameliorates the renal injury in a mouse unilateral ureteral obstruction (UUO) model, whereas the underlying mechanisms are not completely understood. Here, we addressed this question. We found that the administration of IGF-1 significantly reduced the severity of the renal fibrosis in UUO. By analyzing purified renal epithelial cells, we found that IGF-1 significantly reduced the apoptotic cell death of renal epithelial cells, seemingly through upregulation of anti-apoptotic protein Bcl-2, at protein but not mRNA level. Bioinformatics analyses and luciferase-reporter assay showed that miR-429 targeted the 3′-UTR of Bcl-2 mRNA to inhibit its protein translation in renal epithelial cells. Moreover, IGF-1 suppressed miR-429 to increase Bcl-2 in renal epithelial cells to improve survival after UUO. Furthermore, inhibition of ERK/MAPK signaling pathway in renal epithelial cells abolished the suppressive effects of IGF-1 on miR-429 activation, and then the enhanced effects on Bcl-2 in UUO. Thus, our data suggest that IGF-1 may protect renal tubular epithelial cells via activation of ERK/MAPK signaling pathway during renal injury. PMID:27301852

  18. Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase.

    PubMed

    Vicente-Vicente, Laura; Sánchez-Juanes, Fernando; García-Sánchez, Omar; Blanco-Gozalo, Víctor; Pescador, Moisés; Sevilla, María A; González-Buitrago, José Manuel; López-Hernández, Francisco J; López-Novoa, José Miguel; Morales, Ana Isabel

    2015-04-16

    Nephrotoxicity limits the therapeutic efficacy of the antineoplastic drug cisplatin. Due to dosage adjustment and appropriate monitoring, most therapeutic courses with cisplatin produce no or minimal kidney damage. However, we studied whether even sub-nephrotoxic dosage of cisplatin poses a potential risk for the kidneys by predisposing to acute kidney injury (AKI), specifically by lowering the toxicity threshold for a second nephrotoxin. With this purpose rats were treated with a single sub-nephrotoxic dosage of cisplatin (3mg/kg, i.p.) and after two days, with a sub-nephrotoxic regime of gentamicin (50mg/kg/day, during 6 days, i.p.). Control groups received only one of the drugs or the vehicle. Renal function and renal histology were monitored throughout the experiment. Cisplatin treatment did not cause any relevant functional or histological alterations in the kidneys. Rats treated with cisplatin and gentamicin, but not those under single treatments, developed an overt renal failure characterized by both renal dysfunction and massive tubular necrosis. In addition, the urinary excretion of fumarylacetoacetase was increased in cisplatin-treated animals at subtoxic doses, which might be exploited as a cisplatin-induced predisposition marker. In fact, the urinary level of fumarylacetoacetase prior to the second nephrotoxin correlated with the level of AKI triggered by gentamicin in predisposed animals. PMID:25677510

  19. Anorexia nervosa, laxative abuse, hypopotassemia and distal renal tubular acidosis.

    PubMed

    Pines, A; Kaplinsky, N; Olchovsky, D; Frankl, O; Goldfarb, D; Iaina, A

    1985-01-01

    A case of anorexia nervosa in a 28-year-old woman with laxative abuse, hypopotassemia and severe metabolic acidosis, is described. The diagnosis of classical renal tubular acidosis, Type I, was confirmed by our inability to decrease urinary pH beyond 5.5 and to increase ammonia excretion during an ammonium chloride loading test. A bicarbonate loading test and normal plasma aldosterone with high renin activity excluded proximal renal tubular acidosis, hyporeninemic-hypoaldosteronemic renal tubular acidosis and Bartter's syndrome. The inability to increase ammonium excretion during severe metabolic acidosis following ammonium chloride loading did not favor the possibility of a transient physiological adaptation of ammoniagenesis at the tubular cell level, related to potassium depletion. Although mental disorder, laxative abuse, abstinence from food intake and severe potassium depletion intermingled in a vicious cycle, we assume that one of the following possibilities may explain the clinical presentation in our patient: either two separated and unrelated disorders, or laxative abuse as the cause of renal tubular acidification impairment. PMID:3972559

  20. Autophagy Induces Prosenescent Changes in Proximal Tubular S3 Segments.

    PubMed

    Baisantry, Arpita; Bhayana, Sagar; Rong, Song; Ermeling, Esther; Wrede, Christoph; Hegermann, Jan; Pennekamp, Petra; Sörensen-Zender, Inga; Haller, Hermann; Melk, Anette; Schmitt, Roland

    2016-06-01

    Evidence suggests that autophagy promotes the development of cellular senescence. Because cellular senescence contributes to renal aging and promotes the progression from AKI to CKD, we investigated the potential effect of tubular autophagy on senescence induction. Compared with kidneys from control mice, kidneys from mice with conditional deletion of autophagy-related 5 (Atg5) for selective ablation of autophagy in proximal tubular S3 segments (Atg5(Δ) (flox/) (Δ) (flox)) presented with significantly less tubular senescence, reduced interstitial fibrosis, and superior renal function 30 days after ischemia/reperfusion injury. To correlate this long-term outcome with differences in the early injury process, kidneys were analyzed 2 hours and 3 days after reperfusion. Notably, compared with kidneys of control mice, Atg5(Δ) (flox/) (Δ) (flox) kidneys showed more cell death in outer medullary S3 segments at 2 hours but less tubular damage and inflammation at day 3. These data suggest that the lack of autophagy prevents early survival mechanisms in severely damaged tubular cells. However, if such compromised cells persist, then they may lead to maladaptive repair and proinflammatory changes, thereby facilitating the development of a senescent phenotype and CKD. PMID:26487561

  1. Wnt4 is a novel biomarker for the early detection of kidney tubular injury after ischemia/reperfusion injury.

    PubMed

    Zhao, Shi-Lei; Wei, Shi-Yao; Wang, Yu-Xiao; Diao, Tian-Tian; Li, Jian-Si; He, Yi-Xin; Yu, Jing; Jiang, Xi-Yue; Cao, Yang; Mao, Xin-Yue; Wei, Qiu-Ju; Wang, Yu; Li, Bing

    2016-01-01

    Earlier intervention after acute kidney injury would promote better outcomes. Our previous study found that Wnt proteins are promptly upregulated after ischemic kidney injury. Thus, we assessed whether Wnt4 could be an early and sensitive biomarker of tubular injury. We subjected mice to bilateral ischemia/reperfusion injury (IRI). Kidney and urinary Wnt4 expression showed an early increase at 3 hours and increased further at 24 hours post-IRI and was closely correlated with histopathological alterations. Serum creatinine slightly increased at 6 hours, indicating that it was less sensitive than Wnt4 expression. These data were further confirmed by clinical study. Both kidney and urinary Wnt4 expression were significantly increased in patients diagnosed with biopsy-proven minimal change disease (MCD) with tubular injury, all of whom nevertheless had normal estimated glomerular filtration rate (eGFR) and serum creatinine. The increased Wnt4 expression also strongly correlated with histopathological alterations in these MCD patients. In conclusion, this is the first demonstration that increases in both kidney and urinary Wnt4 expression can be detected more sensitively and earlier than serum creatinine after kidney injury. In particular, urinary Wnt4 could be a potential noninvasive biomarker for the early detection of tubular injury. PMID:27600466

  2. Wnt4 is a novel biomarker for the early detection of kidney tubular injury after ischemia/reperfusion injury

    PubMed Central

    Zhao, Shi-Lei; Wei, Shi-Yao; Wang, Yu-Xiao; Diao, Tian-Tian; Li, Jian-Si; He, Yi-Xin; Yu, Jing; Jiang, Xi-Yue; Cao, Yang; Mao, Xin-Yue; Wei, Qiu-Ju; Wang, Yu; Li, Bing

    2016-01-01

    Earlier intervention after acute kidney injury would promote better outcomes. Our previous study found that Wnt proteins are promptly upregulated after ischemic kidney injury. Thus, we assessed whether Wnt4 could be an early and sensitive biomarker of tubular injury. We subjected mice to bilateral ischemia/reperfusion injury (IRI). Kidney and urinary Wnt4 expression showed an early increase at 3 hours and increased further at 24 hours post-IRI and was closely correlated with histopathological alterations. Serum creatinine slightly increased at 6 hours, indicating that it was less sensitive than Wnt4 expression. These data were further confirmed by clinical study. Both kidney and urinary Wnt4 expression were significantly increased in patients diagnosed with biopsy-proven minimal change disease (MCD) with tubular injury, all of whom nevertheless had normal estimated glomerular filtration rate (eGFR) and serum creatinine. The increased Wnt4 expression also strongly correlated with histopathological alterations in these MCD patients. In conclusion, this is the first demonstration that increases in both kidney and urinary Wnt4 expression can be detected more sensitively and earlier than serum creatinine after kidney injury. In particular, urinary Wnt4 could be a potential noninvasive biomarker for the early detection of tubular injury. PMID:27600466

  3. Mucinous tubular and spindle cell carcinoma of the kidney: A case report and review of the literature.

    PubMed

    Sun, Nao; Fu, Yaowen; Wang, Yuantao; Tian, Tengzheng; An, Wei; Yuan, Tong

    2014-03-01

    Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an unusual renal tumor. It is important to increase the recognition of MTSCC-K and improve the level of clinical diagnosis. The current study presents a case of MTSCC-K with clinical, imaging and pathological examination. A 60-year-old female presented to the First Hospital of Jilin University suffering from lumbodorsalgia on the right side for approximately one month, without gross hematuria and fever. Imaging examination by abdominal computed tomography scan revealed a ~6.5×5.0-cm solid mass in the inferior pole of the right kidney. The patient underwent laparoscopic radical resection of the right kidney. Pathological examination showed that the tumor was composed of small, elongated cords or tubules, in a tightly packed arrangement. Myxoid stroma was shown to be interspersed among the tubular cells, and appeared to exhibit slender tubular spindle cell-like structures. Tumor cells were smaller and cube-shaped or oval, with single small eosinophilic nucleoli and low-grade nuclei. Occasionally, necrosis and foam cell infiltration were observed. Myxoid stroma was stained by acidic mucus. Immunohistochemical markers, including CK7, CK19, EMA, Vimentin and P504S (AMACR) showed positive expression in tumoral cells, but the tumoral cells were CD10-negative. The MTSCC-K is a low-grade polymorphic renal epithelial neoplasm, which may be diagnosed by immunohistochemistry. The patients are likely to have an improved prognosis following surgery compared with patients with other renal cell carcinomas. PMID:24520298

  4. Epinephrine Injection Associated Scrotal Skin Necrosis

    PubMed Central

    Gul, Murat; Kaynar, Mehmet; Sekmenli, Tamer; Ciftci, Ilhan; Goktas, Serdar

    2015-01-01

    Male circumcision is among the most frequent surgical interventions throughout history. Although considered as a minor intervention, it may have complications ranging from insignificant to catastrophic. These complications can be attributed to the surgical procedure and anesthesia. In this report we present two cases of scrotal skin necrosis after lidocaine with epinephrine injection using subcutaneous ring block technique prior to circumcision. PMID:26185706

  5. Pythium Root Rot (and Feeder Root Necrosis)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pythium species cause a number of diseases on corn. Among the Pythium diseases, root rot presents the least conspicuous aboveground symptoms. Broadly defined, root rot also includes feeder root necrosis. At least 16 species of Pythium are known to cause root rot of corn. These include P. acanthicu...

  6. Extremely strong tubular stacking of aromatic oligoamide macrocycles

    SciTech Connect

    Kline, Mark A.; Wei, Xiaoxi; Horner, Ian J.; Liu, Rui; Chen, Shuang; Chen, Si; Yung, Ka Yi; Yamato, Kazuhiro; Cai, Zhonghou; Bright, Frank V.; Zeng, Xiao Cheng; Gong, Bing

    2015-01-01

    As the third-generation rigid macrocycles evolved from progenitor 1, cyclic aromatic oligoamides 3, with a backbone of reduced constraint, exhibit extremely strong stacking with an astoundingly high affinity (estimated lower limit of Kdimer > 1013 M-1 in CHCl3), which leads to dispersed tubular stacks that undergo further assembly in solution. Computational study reveals a very large binding energy (-49.77 kcal mol-1) and indicates highly cooperative local dipole interactions that account for the observed strength and directionality for the stacking of 3. In the solid-state, X-ray diffraction (XRD) confirms that the aggregation of 3 results in well-aligned tubular stacks. The persistent tubular assemblies of 3, with their non-deformable sub-nm pore, are expected to possess many interesting functions. One such function, transmembrane ion transport, is observed for 3.

  7. Extremely strong tubular stacking of aromatic oligoamide macrocycles

    SciTech Connect

    Kline, Mark A.; Wei, Xiaoxi; Horner, Ian J.; Liu, Rui; Chen, Shuang; Chen, Si; Yung, Ka Yi; Yamato, Kazuhiro; Cai, Zhonghou; Bright, Frank V.; Zeng, Xiao Cheng; Gong, Bing

    2014-09-16

    As the third-generation rigid macrocycles evolved from progenitor 1, cyclic aromatic oligoamides 3, with a backbone of reduced constraint, exhibit extremely strong stacking with an astoundingly high affinity (estimated lower limit of K-dimer > 1013 M-1 in CHCl3), which leads to dispersed tubular stacks that undergo further assembly in solution. Computational study reveals a very large binding energy (-49.77 kcal mol-1) and indicates highly cooperative local dipole interactions that account for the observed strength and directionality for the stacking of 3. In the solid-state, X-ray diffraction (XRD) confirms that the aggregation of 3 results in well-aligned tubular stacks. Furthermore, the persistent tubular assemblies of 3, with their non-deformable sub-nm pore, are expected to possess many interesting functions. One such function, transmembrane ion transport, is observed for 3.

  8. Open–closed switching of synthetic tubular pores

    PubMed Central

    Kim, Yongju; Kang, Jiheong; Shen, Bowen; Wang, Yanqiu; He, Ying; Lee, Myongsoo

    2015-01-01

    While encouraging progress has been made on switchable nanopores to mimic biological channels and pores, it remains a great challenge to realize long tubular pores with a dynamic open–closed motion. Here we report μm-long, dynamic tubular pores that undergo rapid switching between open and closed states in response to a thermal signal in water. The tubular walls consist of laterally associated primary fibrils stacked from disc-shaped molecules in which the discs readily tilt by means of thermally regulated dehydration of the oligoether chains placed on the wall surfaces. Notably, this pore switching mediates a controlled water-pumping catalytic action for the dehydrative cyclization of adenosine monophosphate to produce metabolically active cyclic adenosine monophosphate. We believe that our work may allow the creation of a variety of dynamic pore structures with complex functions arising from open–closed motion. PMID:26456695

  9. Extremely strong tubular stacking of aromatic oligoamide macrocycles

    DOE PAGESBeta

    Kline, Mark A.; Wei, Xiaoxi; Horner, Ian J.; Liu, Rui; Chen, Shuang; Chen, Si; Yung, Ka Yi; Yamato, Kazuhiro; Cai, Zhonghou; Bright, Frank V.; et al

    2014-09-16

    As the third-generation rigid macrocycles evolved from progenitor 1, cyclic aromatic oligoamides 3, with a backbone of reduced constraint, exhibit extremely strong stacking with an astoundingly high affinity (estimated lower limit of K-dimer > 1013 M-1 in CHCl3), which leads to dispersed tubular stacks that undergo further assembly in solution. Computational study reveals a very large binding energy (-49.77 kcal mol-1) and indicates highly cooperative local dipole interactions that account for the observed strength and directionality for the stacking of 3. In the solid-state, X-ray diffraction (XRD) confirms that the aggregation of 3 results in well-aligned tubular stacks. Furthermore, themore » persistent tubular assemblies of 3, with their non-deformable sub-nm pore, are expected to possess many interesting functions. One such function, transmembrane ion transport, is observed for 3.« less

  10. Extremely strong tubular stacking of aromatic oligoamide macrocycles

    DOE PAGESBeta

    Kline, Mark A.; Wei, Xiaoxi; Horner, Ian J.; Liu, Rui; Chen, Shuang; Chen, Si; Yung, Ka Yi; Yamato, Kazuhiro; Cai, Zhonghou; Bright, Frank V.; et al

    2015-01-01

    As the third-generation rigid macrocycles evolved from progenitor 1, cyclic aromatic oligoamides 3, with a backbone of reduced constraint, exhibit extremely strong stacking with an astoundingly high affinity (estimated lower limit of Kdimer > 1013 M-1 in CHCl3), which leads to dispersed tubular stacks that undergo further assembly in solution. Computational study reveals a very large binding energy (-49.77 kcal mol-1) and indicates highly cooperative local dipole interactions that account for the observed strength and directionality for the stacking of 3. In the solid-state, X-ray diffraction (XRD) confirms that the aggregation of 3 results in well-aligned tubular stacks. The persistentmore » tubular assemblies of 3, with their non-deformable sub-nm pore, are expected to possess many interesting functions. One such function, transmembrane ion transport, is observed for 3.« less

  11. Power generation characteristics of tubular type SOFC by wet process

    SciTech Connect

    Tajiri, H.; Nakayama, T.; Kuroishi, M.

    1996-12-31

    The development of a practical solid oxide fuel cell requires improvement of a cell performance and a cell manufacturing technology suitable for the mass production. In particular tubular type SOFC is thought to be superior in its reliability because its configuration can avoid the high temperature sealing and reduce the thermal stress resulting from the contact between cells. The authors have fabricated a tubular cell with an air electrode support by a wet processing technique, which is suitable for mass production in improving a power density. To enhance the power output of the module, the Integrated Tubular-Type (ITT) cell has been developed. This paper reports the performance of the single cells with various active anode areas and the bundle with series-connected 9-ITT cells with an active anode area of 840 cm{sup 2}.

  12. Mechanisms of albumin uptake by proximal tubular cells.

    PubMed

    Brunskill, N

    2001-01-01

    The likely role of albumin in the induction tubulo-interstitial injury in proteinuria has stimulated considerable interest in the entry of albumin into the proximal tubule and its subsequent uptake by proximal tubular cells. Currently, there is considerable controversy over the degree of glomerular permeability to albumin. After filtration, however, albumin binds to megalin and cubulin, two giant receptors in the apical membrane of proximal tubular cells. Albumin is subsequently re-absorbed by proximal tubular cells by receptor-mediated endocytosis, a process subject to complex regulation. The interaction of albumin with proximal tubule cells also leads to the generation of intracellular signals. The understanding of these pathways may provide important insights into the pathogenesis of renal scarring in proteinuria. PMID:11158855

  13. Klinefelter's syndrome with renal tubular acidosis: impact on height.

    PubMed

    Jebasingh, F; Paul, T V; Spurgeon, R; Abraham, S; Jacob, J J

    2010-02-01

    A 19-year-old Indian man presented with a history of proximal muscle weakness, knock knees and gynaecomastia. On examination he had features of rickets and bilateral small testes. Karyotyping revealed a chromosomal pattern of 47,XXX, confirming the diagnosis of Klinefelter's syndrome. He was also found to have hyperchloraemic metabolic acidosis with hypokalaemia, hypophosphataemia, phosphaturia and glycosuria, which favoured a diagnosis of proximal renal tubular acidosis. Patients with Klinefelter's syndrome typically have a tall stature due to androgen deficiency, resulting in unfused epiphyses and an additional X chromosome. However, this patient had a short stature due to associated proximal renal tubular acidosis. To the best of our knowledge, this is the second case of Klinefelter's syndrome with short stature due to associated renal tubular acidosis reported in the literature. This report highlights the need to consider other causes when patients with Klinefelter's syndrome present with a short stature. PMID:20358137

  14. Dioclea violacea lectin ameliorates oxidative stress and renal dysfunction in an experimental model of acute kidney injury

    PubMed Central

    Freitas, Flavia PS; Porto, Marcella L; Tranhago, Camilla P; Piontkowski, Rogerio; Miguel, Emilio C; Miguel, Thaiz BAR; Martins, Jorge L; Nascimento, Kyria S; Balarini, Camille M; Cavada, Benildo S; Meyrelles, Silvana S; Vasquez, Elisardo C; Gava, Agata L

    2015-01-01

    Acute kidney injury (AKI) is characterized by rapid and potentially reversible decline in renal function; however, the current management for AKI is nonspecific and associated with limited supportive care. Considering the need for more novel therapeutic approaches, we believe that lectins from Dioclea violacea (Dvl), based on their anti-inflammatory properties, could be beneficial for the treatment of AKI induced by renal ischemia/reperfusion (IR). Dvl (1 mg/kg, i.v.) or vehicle (100 µL) was administered to Wistar rats prior to the induction of bilateral renal ischemia (45 min). Following 24 hours of reperfusion, inulin and para-aminohippurate (PAH) clearances were performed to determine glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF) and renal vascular resistance (RVR). Renal inflammation was assessed using myeloperoxidase (MPO) activity. Kidney sections were stained with hematoxylin-eosin to evaluate morphological changes. Intracellular superoxide anions, hydrogen peroxide, peroxynitrite, nitric oxide and apoptosis were analyzed using flow cytometry. IR resulted in diminished GFR, RPF, RBF, and increased RVR; however, these changes were ameliorated in rats receiving Dvl. AKI-induced histomorphological changes, such as tubular dilation, tubular necrosis and proteinaceous casts, were attenuated by Dvl administration. Treatment with Dvl resulted in diminished renal MPO activity, oxidative stress and apoptosis in rats submitted to IR. Our data reveal that Dvl has a protective effect in the kidney, improving renal function after IR injury, probably by reducing neutrophil recruitment and oxidative stress. These results indicate that Dvl can be considered a new therapeutic approach for AKI-induced kidney injury. PMID:26885258

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

    PubMed

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

    2014-11-01

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

  16. DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells

    PubMed Central

    Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

    2014-01-01

    Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or “reperfusion” of renal proximal tubular cells (RPTCs) after ATP-depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP-depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death. PMID:24726884

  17. Hot fire test results of subscale tubular combustion chambers

    NASA Technical Reports Server (NTRS)

    Kazaroff, John M.; Jankovsky, Robert S.; Pavli, Albert J.

    1992-01-01

    Advanced, subscale, tubular combustion chambers were built and test fired with hydrogen-oxygen propellants to assess the increase in fatigue life that can be obtained with this type of construction. Two chambers were tested: one ran for 637 cycles without failing, compared to a predicted life of 200 cycles for a comparable smooth-wall milled-channel liner configuration. The other chamber failed at 256 cycles, compared to a predicted life of 118 cycles for a comparable smooth-wall milled-channel liner configuration. Posttest metallographic analysis determined that the strain-relieving design (structural compliance) of the tubular configuration was the cause of this increase in life.

  18. Regulation of TLR2 and NLRP3 in Primary Murine Renal Tubular Epithelial Cells

    PubMed Central

    Kasimsetty, Sashi G.; DeWolf, Sean E.; Shigeoka, Alana A.; McKay, Dianne B.

    2016-01-01

    Pattern recognition receptors (PRRs) are now recognized to be key triggers of injury in a variety of renal diseases. Several families of these receptors are present in the kidney, and recent data suggest that they are differentially expressed and regulated in the kidney. This study evaluated the interaction between two distinct PRRs that are expressed in the kidney, i.e. TLR2 (Toll-like receptor 2) and the NLRP3 inflammasome. The regulation and activation of these receptors in primary renal tubular epithelial (RTE) cells from murine kidneys were evaluated. RTE cells were extracted from WT and NLRP3-mutant mice and treated ex vivo with ligands specific for TLR2 or NLRP3. We found that TLR2 upregulated NLRP3 as well as its substrate IL-1β, and that signaling through the NLRP3 inflammasome induced RTE cell necrosis. The results of this study suggest a previously unknown interaction between TLR2 and NLRP3 in primary RTE cells and highlight the importance of the cross talk that occurs in kidney-related PRRs. Understanding how PRRs are regulated is important for the design of rationale therapeutic strategies to modulate these receptors in renal disease. PMID:25343834

  19. Imaging of acute pancreatitis and its complications. Part 2: complications of acute pancreatitis.

    PubMed

    Türkvatan, A; Erden, A; Türkoğlu, M A; Seçil, M; Yüce, G

    2015-02-01

    The Atlanta classification of acute pancreatitis was introduced in 1992 and divides patients into mild and severe groups based on clinical and biochemical criteria. Recently, the terminology and classification scheme proposed at the initial Atlanta Symposium have been reviewed and a new consensus statement has been proposed by the Acute Pancreatitis Classification Working Group. Major changes include subdividing acute fluid collections into "acute peripancreatic fluid collection" and "acute post-necrotic pancreatic/peripancreatic fluid collection (acute necrotic collection)" based on the presence of necrotic debris. Delayed fluid collections have been similarly subdivided into "pseudocyst" and "walled of pancreatic necrosis". Appropriate use of the new terms describing the fluid collections is important for management decision-making in patients with acute pancreatitis. The purpose of this review article is to present an overview of complications of the acute pancreatitis with emphasis on their prognostic significance and impact on clinical management and to clarify confusing terminology for pancreatic fluid collections. PMID:24703377

  20. Infected pancreatic necrosis and peripancreatic fluid collections: serendipitous response to antibiotics and medical therapy in three patients.

    PubMed

    Dubner, H; Steinberg, W; Hill, M; Bassi, C; Chardavoyne, R; Bank, S

    1996-04-01

    Three patients with clinical and radiologic evidence of pancreatic necrosis or peripancreatic fluid collections/inflammatory masses who were advised to have surgery on the basis of bacterial infection on skinny-needle aspiration of the pancreas but were deemed medically unstable or refused operative intervention were treated with intensive antibiotic therapy. All three patients survived the attack of acute pancreatitis with infection on medical therapy alone. This suggests that occasional patients with infected necrosis and/or peripancreatic collections/inflammatory masses may respond to antibiotics, especially those antibiotics that have recently been shown to have a high penetration into pancreatic tissue. PMID:8830338

  1. Statin-induced muscle necrosis in the rat: distribution, development, and fibre selectivity.

    PubMed

    Westwood, F Russell; Bigley, Alison; Randall, Kevin; Marsden, Alan M; Scott, Robert C

    2005-01-01

    Simvastatin and cerivastatin have been used to investigate the development of statin-induced muscle necrosis in the rat. This was similar for both statins and was treatment-duration dependent, only occurring after 10 days had elapsed even if the dose was increased, and still occurring after this time when dosing was terminated earlier as a result of morbidity. It was then widespread and affected all areas of the muscular system. However, even when myotoxicity was severe, particular individual muscles and some types of fibres within affected muscles were spared consistently. Fibre typing of spared muscles and of acutely necrotic fibres within affected muscles indicated a differential fibre sensitivity to statin-induced muscle necrosis. The fibres showed a necrotic response to statin administration that matched their oxidative/glycolytic metabolic nature: Least sensitive --> I < - > IIA < - > IID < - > IIB <-- most sensitive. Type I and IIB fibres represent metabolic extremes of a continuum of metabolic properties through the fibre types with type I fibres most oxidative in metabolism and type IIB fibres most glycolytic. In addition, in some (nonnecrotic) glycolytic fibres from muscles showing early multifocal single fibre necrosis the only subcellular alterations present in isolation of any other changes were mitochondrial. These changes were characterised by an increased incidence of vacuolation and the formation of myelinoid vesicular bodies that accumulated in the subsarcolemmal areas. These findings suggest an important early involvement of mitochondria in selective glycolytic muscle fibre necrosis following inhibition of the enzyme HMG-CoA reductase. PMID:15902968

  2. The role of AT1 and AT2 angiotensin receptors in the mechanism of apoptosis in renal tubular cells after physical exercise.

    PubMed

    Podhorska-Okołów, M; Dziegiel, P; Gomułkiewicz, A; Dolińska-Krajewska, B; Murawska-Ciałowicz, E; Jethon, Z; Zabel, M

    2004-01-01

    Intensive physical exercise disturbs the entire homeostasis in the body and leads to changes in haemodynamic and metabolic alterations not only in skeletal muscles but also in many distant organs. In response to acute physical exercise, a decrease of the glomerular filtration may occur, followed by stimulation of the renin-angiotensin system (RAS). Recent studies have shown that both AT1 and AT2 angiotensin receptors may play a role in mediating the apoptotic process in the kidney. Our previous studies have demonstrated an occurrence of apoptosis in rat renal tubular cells after an excessive exercise. The aim of the present study was to determine the possible mechanism of exercise-induced apoptosis in rat kidney. The analysis was performed on kidneys of rats, subjected to treadmill running until exhaustion. Apoptosis was detected in paraffin sections by the TUNEL technique. The expression of AT1 and AT2 receptors in renal tubular cells was examined by immunohistochemistry and Western blot. Our results confirmed that apoptosis after physical exercise is present in renal distal tubular cells. Moreover, there was an increased expression of AT1 and AT2 receptors in distal tubular cells. These studies suggest that physical exercise may induce apoptosis by a mechanism, involving the activation of angiotensin AT1 and AT2 receptors. PMID:15638358

  3. Coiled sheet metal strip opens into tubular configuration

    NASA Technical Reports Server (NTRS)

    Park, J. J.

    1966-01-01

    Copper alloy is converted into a spring material that can be rolled into a compact coil which will spontaneously open to form a tube in the long direction of the strip. The copper alloy is passed through a furnace at a prescribed temperature while restraining the strip in the desired tubular configuration.

  4. Rapid magnetic cell delivery for large tubular bioengineered constructs.

    PubMed

    Gonzalez-Molina, J; Riegler, J; Southern, P; Ortega, D; Frangos, C C; Angelopoulos, Y; Husain, S; Lythgoe, M F; Pankhurst, Q A; Day, R M

    2012-11-01

    Delivery of cells into tubular tissue constructs with large diameters poses significant spatial and temporal challenges. This study describes preliminary findings for a novel process for rapid and uniform seeding of cells onto the luminal surface of large tubular constructs. Fibroblasts, tagged with superparamagnetic iron oxide nanoparticles (SPION), were directed onto the luminal surface of tubular constructs by a magnetic field generated by a k4-type Halbach cylinder device. The spatial distribution of attached cells, as measured by the mean number of cells, was compared with a conventional, dynamic, rotational cell-delivery technique. Cell loading onto the constructs was measured by microscopy and magnetic resonance imaging. The different seeding techniques employed had a significant effect on the spatial distribution of the cells (p < 0.0001). The number of attached cells at defined positions within the same construct was significantly different for the dynamic rotation technique (p < 0.05). In contrast, no significant differences in the number of cells attached to the luminal surface were found between the defined positions on the construct loaded with the Halbach cylinder. The technique described overcomes limitations associated with existing cell-delivery techniques and is amenable to a variety of tubular organs where rapid loading and uniform distribution of cells for therapeutic applications are required. PMID:22696487

  5. An Improved Design of a Simple Tubular Reactor Experiment.

    ERIC Educational Resources Information Center

    Asfour, Abdul-Fattah A.

    1985-01-01

    Background information, procedures used, and typical results obtained are provided for an experiment which: (1) examines the effect of residence time on conversion in a tubular flow reactor; and (2) compares the experimental conversions with those obtained from plug-flow and laminar-flow reactor models. (JN)

  6. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

    PubMed Central

    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

    Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. PMID:27293888

  7. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy.

    PubMed

    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

    Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. PMID:27293888

  8. Regulated necrosis and its implications in toxicology.

    PubMed

    Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi

    2015-07-01

    Recent research developments have revealed that caspase-dependent apoptosis is not the sole form of regulated cell death. Caspase-independent, but genetically regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and the recently discovered ferroptosis and autosis. Importantly, regulated necrosis can be modulated by small molecule inhibitors/activators, confirming the cell autonomous mechanism of these forms of cell death. The success of small molecule-mediated manipulation of regulated necrosis has produced great changes in the field of cell death research, and has also brought about significant changes in the fields of pharmacology as well as toxicology. In this review, we intend to summarize the modes of regulated cell death other than apoptosis, and discuss their implications in toxicology. PMID:25865964

  9. Giant cell arteritis presenting as scalp necrosis.

    PubMed

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

    2011-01-01

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

  10. New cancer therapies and jaw necrosis.

    PubMed

    Patel, V; Kelleher, M; Sproat, C; Kwok, J; McGurk, M

    2015-09-11

    Osteonecrosis of the jaw (ONJ) has a number of causes, the most familiar being radiation or bisphosphonate induced. Various other novel anti-neoplastic and bone-targeting therapies that can also cause jaw necrosis have recently become available. This has led to the suggested acronym MRONJ for medication-related osteonecrosis of the jaw. This article summarises the available information on these drugs and their implications for the dental surgeon. PMID:26361116

  11. Uterine Necrosis Associated with Fusobacterium necrophorum Infection

    PubMed Central

    Widelock, T.; Elkattah, R.; Gibbs, S.; Mashak, Z.; Mohling, S.; DePasquale, S.

    2015-01-01

    Fusobacterium necrophorum is infrequently implicated as a pathogenic organism. When pathogenic, the typical clinical presentation is that of pharyngitis, cervical adenopathy, and unilateral thrombophlebitis of the internal jugular vein. Infections caused by Fusobacterium necrophorum within the fields of obstetrics and gynecology have been infrequently reported. We describe a 19-year-old woman who underwent a cesarean delivery complicated by sepsis and purulent uterine necrosis secondary to Fusobacterium necrophorum infection. PMID:26000185

  12. Idiopathic incus necrosis: Analysis of 4 cases.

    PubMed

    Kansu, Leyla; Yilmaz, Ismail; Akdogan, Volkan; Avci, Suat; Ozluoglu, Levent

    2013-02-01

    We evaluated ossicular chain reconstruction in patients with idiopathic incus necrosis who have conductive hearing loss and an intact ear drum. The study included four patients (3 women and 1 man; the ages of the patients were 22, 31, 35, and 56 years, respectively) with unilateral conductive hearing loss, no history of chronic serous otitis media, an intact ear drum, normal middle ear mucosa, and necrosis of the long processes of the incus. On preoperative pure tone audiometry, air-bone gaps were 24, 25, 38, and 33 dB. Bilateral tympanometry and temporal bone computed tomography results were normal. All 4 patients underwent an exploratory tympanotomy. During the operation, the mucosa of the middle ear was normal, with a mobile stapes foot plate and malleus. No evidence of any granulation tissue was found; however, necrosis of the incus long processes was seen. For ossicular reconstruction, we used tragal cartilage between the incus and the stapes in 1 patient; in the other 3 patients, glass ionomer bone cement was used (an interposition cartilage graft also was used in the patients who received the glass ionomer bone cement). In all patients, air-bone gaps under 20 dB were established in the first year after surgery. In the ossicular disorders within the middle ear, the incus is the most commonly affected ossicle. While, the most common cause of these disorders is chronic otitis media, it may be idiopathic rarely. Several ossicular reconstruction techniques have been used to repair incudostapedial discontinuity. PMID:23460219

  13. Acute Bronchitis

    MedlinePlus

    ... or though physical contact (for example, on unwashed hands). Being exposed to tobacco smoke, air pollution, dusts, vapors, and fumes can also cause acute bronchitis. Less often, bacteria can also cause acute bronchitis. To diagnose acute ...

  14. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  15. Successful treatment of multidrug-resistant tuberculosis following drug-induced hepatic necrosis requiring liver transplant.

    PubMed

    Marra, F; Cox, V C; FitzGerald, J M; Moadebi, S; Elwood, R K

    2004-07-01

    A 28-year-old female developed multidrug-resistant (MDR) tuberculous lymphadenitis following a trip to India. She was initially treated with a four-drug regimen of first-line anti-tuberculosis medications, but when sensitivities indicated resistance to isoniazid and rifampin, her regimen was altered to ciprofloxacin (CFX), pyrazinamide (PZA) and ethambutol. She subsequently developed a rash, flu-like symptoms and fever, which progressed to acute hepatic necrosis despite discontinuation of medication. The clinical presentation and subsequent investigations suggested a hypersensitivity reaction, possibly related to the quinolone. The patient subsequently had an orthoptic liver transplant; second-line anti-tuberculosis medications were restarted to which she responded clinically and radiologically. Our findings raise the possibility that the CFX and PZA combination was responsible for the hepatic necrosis. The patient also illustrates that active, even MDR tuberculosis is not a contraindication to hepatic transplant. PMID:15260286

  16. Vitamin C Attenuates Hemorrhagic Shock-induced Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Nonintegrin Expression in Tubular Epithelial Cells and Renal Injury in Rats

    PubMed Central

    Ma, Li; Fei, Jian; Chen, Ying; Zhao, Bing; Yang, Zhi-Tao; Wang, Lu; Sheng, Hui-Qiu; Chen, Er-Zhen; Mao, En-Qiang

    2016-01-01

    Background: The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock (HS) is unknown. The present study aimed to investigate this phenomenon and the inhibitory effect of Vitamin C (VitC). Methods: A Sprague–Dawley rat HS model was established in vivo in this study. The expression level and location of DC-SIGN were observed in kidneys. Also, the degree of histological damage, the concentrations of tumor necrosis factor-α and interleukin-6 in the renal tissues, and the serum concentration of blood urea nitrogen and creatinine at different times (2–24 h) after HS (six rats in each group), with or without VitC treatment before resuscitation, were evaluated. Results: HS induced DC-SIGN expression in rat tubular epithelial cells. The proinflammatory cytokine concentration, histological damage scores, and functional injury of kidneys had increased. All these phenomena induced by HS were relieved when the rats were treated with VitC before resuscitation. Conclusions: The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN, and the levels of proinflammatory cytokines in the kidney tissues improved correspondingly. The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney. PMID:27411463

  17. Factors modifying renal tubular bicarbonate reabsorption in the dog

    PubMed Central

    Ullmann, Elisabeth

    1968-01-01

    1. Acute experiments were carried out on anaesthetized dogs during metabolic alkalosis produced by I.V. administration of NaHCO3. Partial constriction of one ureter led to a significant rise in the HCO3- threshold, beyond the simultaneous value for the other kidney. The magnitude of the increase was not correlated with the reduction of glomerular filtration. 2. Stop-flow analysis, following complete unilateral obstruction of urine flow, demonstrated proximal as well as distal tubular reabsorption of bicarbonate. At any given plasma Pco2 the detailed configuration of the concentration changes which developed depended on (a) the presence and concentration of mannitol, (b) the duration of urinary stasis, and (c) the plasma concentration of HCO3-. 3. If a solution containing 15% (w/v) mannitol was infused I.V., the HCO3- concentration in free flow urine was lower than in plasma, and it fell further during arrest of flow in the entire column of trapped fluid. If less mannitol was infused, or none at all, interruption of urine flow led to a striking increase of HCO3- concentration in the distal portion of the occluded column, and to a fall in the fluid arrested in the proximal segments. 4. It was demonstrated that the HCO3- concentration attained after 2½, 6, or 15 min of urinary stasis at any point in the trapped fluid column was due to the combined effects of water reabsorption and HCO3- reabsorption which proceeded independently, and with a different time course. 5. If mannitol was administered the lowest urinary HCO3- concentration in the series moved progressively to a more distal location with increasing duration of urinary stasis. When HCO3- concentration peaks were present in distal fluid they were conspicuous only after short interruptions of urine flow; during extended stop-flow periods they became attenuated, or disappeared. If no mannitol was administered this did not occur. 6. Provided the plasma level of HCO3- was sufficiently elevated, mannitol (15%, w

  18. Peritubular capillary dysfunction and renal tubular epithelial cell stress following lipopolysaccharide administration in mice.

    PubMed

    Wu, Liping; Tiwari, Manish M; Messer, Kurt J; Holthoff, Joseph H; Gokden, Neriman; Brock, Robert W; Mayeux, Philip R

    2007-01-01

    The mortality rate for septic patients with acute renal failure is extremely high. Since sepsis is often caused by lipopolysaccharide (LPS), a model of LPS challenge was used to study the development of kidney injury. Intravital video microscopy was utilized to investigate renal peritubular capillary blood flow in anesthetized male C57BL/6 mice at 0, 2, 6, 10, 18, 24, 36, and 48 h after LPS administration (10 mg/kg ip). As early as 2 h, capillary perfusion was dramatically compromised. Vessels with continuous flow were decreased from 89 +/- 4% in saline controls to 57 +/- 5% in LPS-treated mice (P < 0.01), and vessels with intermittent flow were increased from 6 +/- 2% to 31 +/- 5% (P < 0.01). At 2 h, mRNA for intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were elevated 50- and 27-fold, respectively, suggesting that vascular inflammation is an early event that may contribute to capillary dysfunction. By 10 h, vessels with no flow increased from 5 +/- 2% in saline controls to 19 +/- 3% in LPS-treated mice (P < 0.05). By 48 h, capillary function was returning toward control levels. The decline in functional capillaries preceded the development of renal failure and was paralleled by induction of inducible nitric oxide synthase in the kidney. Using NAD(P)H autofluorescence as an indicator of cellular redox stress, we found that tubular cell stress was highly correlated with the percentage of dysfunctional capillaries (r(2) = 0.8951, P < 0.0001). These data show that peritubular capillary dysfunction is an early event that contributes to tubular stress and renal injury. PMID:16926442

  19. Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass

    PubMed Central

    Wang, Xiaocou; Xue, Qinghua; Yan, Fuxia; Liu, Jinping; Li, Shoujun; Hu, Shengshou

    2015-01-01

    Objective Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF). This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass. Methods Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6), the control group (Group C, n = 6), and the sham operation group (Group S, n = 6), and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG) from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected. Results The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation

  20. Renal Papillary Necrosis Appearing as Bladder Cancer on Imaging

    PubMed Central

    Dagrosa, Lawrence M.; Gormley, Elizabeth Ann

    2016-01-01

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

  1. Renal Integrin-Linked Kinase Depletion Induces Kidney cGMP-Axis Upregulation: Consequences on Basal and Acutely Damaged Renal Function

    PubMed Central

    Cano-Peñalver, José Luis; Griera, Mercedes; García-Jerez, Andrea; Hatem-Vaquero, Marco; Ruiz-Torres, María Piedad; Rodríguez-Puyol, Diego; de Frutos, Sergio; Rodríguez-Puyol, Manuel

    2015-01-01

    Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and produces cGMP, which activates cGMP-dependent protein kinases (PKG) and is hydrolyzed by specific phosphodiesterases (PDE). The vasodilatory and cytoprotective capacity of cGMP-axis activation results in a therapeutic strategy for several pathologies. Integrin-linked kinase (ILK), a major scaffold protein between the extracellular matrix and intracellular signaling pathways, may modulate the expression and functionality of the cGMP-axis–related proteins. We introduce ILK as a novel modulator in renal homeostasis as well as a potential target for cisplatin (CIS)-induced acute kidney injury (AKI) improvement. We used an adult mice model of depletion of ILK (cKD-ILK), which showed basal increase of sGC and PKG expressions and activities in renal cortex when compared with wildtype (WT) littermates. Twenty-four h activation of sGC activation with NO enhanced the filtration rate in cKD-ILK. During AKI, cKD-ILK maintained the cGMP-axis upregulation with consequent filtration rates enhancement and ameliorated CIS-dependent tubular epithelial-to-mesenchymal transition and inflammation and markers. To emphasize the role of cGMP-axis upregulation due to ILK depletion, we modulated the cGMP axis under AKI in vivo and in renal cultured cells. A suboptimal dose of the PDE inhibitor ZAP enhanced the beneficial effects of the ILK depletion in AKI mice. On the other hand, CIS increased contractility-related events in cultured glomerular mesangial cells and necrosis rates in cultured tubular cells; ILK depletion protected the cells while sGC blockade with ODQ fully recovered the damage. PMID:26562149

  2. Tracheal necrosis with surgical emphysema following thyroidectomy.

    PubMed

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

    2009-01-01

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

  3. Testing composite-to-metal tubular lap joints

    NASA Astrophysics Data System (ADS)

    Guess, T. R.; Reedy, E. D., Jr.; Slavin, A. M.

    Procedures were developed to fabricate, nondestructively evaluate, and mechanically test composite-to-metal tubular joints. The axially loaded tubular lap joint specimen consisted of two metal tubes bonded within each end of a fiberglass composite tube. Joint specimens with both tapered and untapered aluminum adherends and a plain weave E-glass/epoxy composite were tested in tension, compression, and flexure. Other specimens with tapered and untapered steel adherends and a triaxially reinforced E-glass/epoxy composite were tested in tension and compression. Test results include joint strength and failure mode data. A finite element analysis of the axially loaded joints explains the effect of adherend geometry and material properties on measured joint strength. The flexural specimen was also analyzed; calculated surface strains are in good agreement with measured values, and joint failure occurs in the region of calculated peak peel stress.

  4. Buckling characteristics of hypersonic aircraft wing tubular panels

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Shideler, John L.; Fields, Roger A.

    1986-01-01

    The buckling characteristics of Rene 41 tubular panels installed as wing panels on a hypersonic wing test structure (HWTS) were determined nondestructively through use of a force/stiffness technique. The nondestructive buckling tests were carried out under different combined load conditions and different temperature environments. Two panels were subsequently tested to buckling failure in a universal tension compression testing machine. In spite of some data scattering because of large extrapolations of data points resulting from termination of the test at a somewhat low applied load, the overall test data correlated fairly well with theoretically predicted buckling interaction curves. The structural efficiency of the tubular panels was slightly higher than that of the beaded panels which they replaced.

  5. Testing composite-to-metal tubular lap joints

    SciTech Connect

    Guess, T.R.; Reedy, E.D. Jr.; Slavin, A.M.

    1993-11-01

    Procedures were developed to fabricate, nondestructively evaluate, and mechanically test composite-to-metal tubular joints. The axially loaded tubular lap joint specimen consisted of two metal tubes bonded within each end of a fiberglass composite tube. Joint specimens with both tapered and untapered aluminum adherends and a plain weave E-glass/epoxy composite were tested in tension, compression, and flexure. Other specimens with tapered and untapered steel adherends and a triaxially reinforced E-glass/epoxy composite were tested in tension and compression. Test results include joint strength and failure mode data. A finite element analysis of the axially loaded joints explains the effect of adherend geometry and material properties on measured joint strength. The flexural specimen was also analyzed; calculated surface strains are in good agreement with measured values, and joint failure occurs in the region of calculated peak peel stress.

  6. Molecular interactions between albumin and proximal tubular cells.

    PubMed

    Brunskill, N J

    1998-01-01

    In glomerular diseases the filtration of excess proteins into the proximal tubule, together with their subsequent reabsorption may represent an important pathological mechanism underlying progressive renal scarring. The most prominent protein in glomerular filtrate, albumin, is reabsorbed by receptor-mediated endocytosis by proximal tubular cells. It binds both to scavenger-type receptors and to megalin in the proximal tubule. Some of these receptors appear to be shared with other cell types, particularly endothelial cells. The endocytic uptake of albumin is subjected to complex hormonal and enzymatic regulation. In addition to being reabsorbed in the proximal tubule, albumin may act as a signalling molecule in these cells, and may induce the expression of numerous pro-inflammatory genes. Modulation of the interaction of albumin with proximal tubular cells may eventually prove to be of therapeutic importance in the treatment of renal diseases. PMID:9807019

  7. [Primary distal renal tubular acidosis: a case report].

    PubMed

    Abdallah, Jihene Ben; Charfeddine, Bassem; Braham, Imen; Neffati, Souhir; Othmen, Leila Ben; Letaief, Affef; Smach, Mohamed Ali; Bourfifa, Zoheier; Dridi, Hedi; Limem, Khalifa

    2011-01-01

    The primary distal renal tubular acidosis is characterized biochemically by the inability of the kidney to produce appropriately acid urine in the presence of systemic metabolic acidosis or after acid loading (e.g. ammonium chloride). It is secondary to defective excretion of H(+) by the cells of the collecting duct. We report the observation of the child MC, 4-year-old, for whom the association of polyuria-polydipsia syndrome, a failure to thrive, nephrolithiasis, hypercalciuria, and especially a high urine pH in the presence of metabolic acidosis did evoke diagnosis of distal renal tubular acidosis. An urine acidification test with ammonium chloride was performed, the urinary pH was always higher than 5.5, thus confirming the diagnosis. PMID:21464016

  8. Dynamic model of microalgal production in tubular photobioreactors.

    PubMed

    Fernández, I; Acién, F G; Fernández, J M; Guzmán, J L; Magán, J J; Berenguel, M

    2012-12-01

    A dynamic model for microalgal culture is presented. The model takes into account the fluid-dynamic and mass transfer, in addition to biological phenomena, it being based on fundamental principles. The model has been calibrated and validated using data from a pilot-scale tubular photobioreactor but it can be extended to other designs. It can be used to determine, from experimental measurements, the values of characteristic parameters. The model also allows a simulation of the system's dynamic behaviour in response to solar radiation, making it a useful tool for design and operation optimization of photobioreactors. Moreover, the model permits the identification of local pH gradients, dissolved oxygen and dissolved carbon dioxide; that can damage microalgae growth. In addition, the developed model can map the different characteristic time scales of phenomena inside microalgae cultures within tubular photobioreactors, meaning it is a valuable tool in the development of advanced control strategies for microalgae cultures. PMID:23073105

  9. Phyllotactic transformations as plastic deformations of tubular crystals with defects

    NASA Astrophysics Data System (ADS)

    Beller, Daniel; Nelson, David

    Tubular crystals are 2D lattices in cylindrical topologies, which could be realized as assemblies of colloidal particles, and occur naturally in biological microtubules and in single-walled carbon nanotubes. Their geometry can be understood in the language of phyllotaxis borrowed from botany. We study the mechanics of plastic deformations in tubular crystals in response to tensile stress, as mediated by the formation and separation of dislocation pairs in a triangular lattice. Dislocation motion allows the growth of one phyllotactic arrangement at the expense of another, offering a low-energy, stepwise mode of plastic deformation in response to external stresses. Through theory and simulation, we examine how the tube's radius and helicity affects, and is in turn altered by, dislocation glide. The crystal's bending modulus is found to produce simple but important corrections to the tube's deformation mechanics.

  10. An early Cambrian agglutinated tubular lophophorate with brachiopod characters

    PubMed Central

    Zhang, Z.-F.; Li, G.-X.; Holmer, L. E.; Brock, G. A.; Balthasar, U.; Skovsted, C. B.; Fu, D.-J.; Zhang, X.-L.; Wang, H.-Z.; Butler, A.; Zhang, Z.-L.; Cao, C.-Q.; Han, J.; Liu, J.-N.; Shu, D.-G.

    2014-01-01

    The morphological disparity of lophotrochozoan phyla makes it difficult to predict the morphology of the last common ancestor. Only fossils of stem groups can help discover the morphological transitions that occurred along the roots of these phyla. Here, we describe a tubular fossil Yuganotheca elegans gen. et sp. nov. from the Cambrian (Stage 3) Chengjiang Lagerstätte (Yunnan, China) that exhibits an unusual combination of phoronid, brachiopod and tommotiid (Cambrian problematica) characters, notably a pair of agglutinated valves, enclosing a horseshoe-shaped lophophore, supported by a lower bipartite tubular attachment structure with a long pedicle with coelomic space. The terminal bulb of the pedicle provided anchorage in soft sediment. The discovery has important implications for the early evolution of lophotrochozoans, suggesting rooting of brachiopods into the sessile lophotrochozoans and the origination of their bivalved bauplan preceding the biomineralization of shell valves in crown brachiopods. PMID:24828016

  11. Evacuated, displacement compression mold. [of tubular bodies from thermosetting plastics

    NASA Technical Reports Server (NTRS)

    Heier, W. C. (Inventor)

    1974-01-01

    A process of molding long thin-wall tubular bodies from thermosetting plastic molding compounds is described wherein the tubular body lengths may be several times the diameters. The process is accomplished by loading a predetermined quantity of molding compound into a female mold cavity closed at one end by a force mandrel. After closing the other end of the female mold with a balance mandrel, the loaded cavity is evacuated by applying a vacuum of from one-to-five mm pressure for a period of fifteen-to-thirty minutes. The mold temperature is raised to the minimum temperature at which the resin constituent of the compound will soften or plasticize and a pressure of 2500 psi is applied.

  12. Optimal startup control of a jacketed tubular reactor.

    NASA Technical Reports Server (NTRS)

    Hahn, D. R.; Fan, L. T.; Hwang, C. L.

    1971-01-01

    The optimal startup policy of a jacketed tubular reactor, in which a first-order, reversible, exothermic reaction takes place, is presented. A distributed maximum principle is presented for determining weak necessary conditions for optimality of a diffusional distributed parameter system. A numerical technique is developed for practical implementation of the distributed maximum principle. This involves the sequential solution of the state and adjoint equations, in conjunction with a functional gradient technique for iteratively improving the control function.

  13. Tubular space truss structure for SKITTER 2 robot

    NASA Technical Reports Server (NTRS)

    Beecham, Richard; Dejulio, Linda; Delorme, Paul; Eck, Eric; Levy, Avi; Lowery, Joel; Radack, Joe; Sheffield, Randy; Stevens, Scott

    1988-01-01

    The Skitter 2 is a three legged transport vehicle designed to demonstrate the principle of a tripod walker in a multitude of environments. The tubular truss model of Skitter 2 is a proof of principal design. The model will replicate the operational capabilities of Skitter 2 including its ability to self-right itself. The project's focus was on the use of light weight tubular members in the final structural design. A strong design for the body was required as it will undergo the most intense loading. Triangular geometry was used extensively in the body, providing the required structural integrity and eliminating the need for cumbersome shear panels. Both the basic femur and tibia designs also relied on the strong geometry of the triangle. An intense literature search aided in the development of the most suitable weld techniques, joints, linkages, and materials required for a durable design. The hinge design features the use of spherical rod end bearings. In order to obtain a greater range of mobility in the tibia, a four-bar linkage was designed which attaches both to the femur and the tibia. All component designs, specifically the body, femur, and the tibia were optimized using the software package IDEAS 3.8A Supertab. The package provided essential deformation and stress analysis information on each component's design. The final structure incurred only a 0.0544 inch deflection in a maximum (worst case) loading situation. The highest stress experienced by any AL6061-T6 tubular member was 1920 psi. The structural integrity of the final design facilitated the use of Aluminum 6061-T6 tubing. The tubular truss structure of Skitter 2 is an effective and highly durable design. All facets of the design are structurally sound and cost effective.

  14. A tubular flux-switching permanent magnet machine

    NASA Astrophysics Data System (ADS)

    Wang, J.; Wang, W.; Clark, R.; Atallah, K.; Howe, D.

    2008-04-01

    The paper describes a novel tubular, three-phase permanent magnet brushless machine, which combines salient features from both switched reluctance and permanent magnet machine technologies. It has no end windings and zero net radial force and offers a high power density and peak force capability, as well as the potential for low manufacturing cost. It is, therefore, eminently suitable for a variety of applications, ranging from free-piston energy converters to active vehicle suspensions.

  15. Mechanical models for the self-organization of tubular patterns

    PubMed Central

    2013-01-01

    Organogenesis, such as long tubule self-organization, requires long-range coordination of cell mechanics to arrange cell positions and to remodel the extracellular matrix. While the current mainstream in the field of tissue morphogenesis focuses primarily on genetics and chemical signaling, the influence of cell mechanics on the programming of patterning cues in tissue morphogenesis has not been adequately addressed. Here, we review experimental evidence and propose quantitative mechanical models by which cells can create tubular patterns. PMID:23719257

  16. Elastomer liners for geothermal tubulars Y267 EPDM Liner Program:

    SciTech Connect

    Hirasuna, A.R.; Davis, D.L.; Flickinger, J.E.; Stephens, C.A.

    1987-12-01

    The elastomer, Y267 EPDM, has been identified as a hydrothermally stable material which can operate at temperatures in excess of 320/sup 0/C. The goal of the Y267 Liner Program was to demonstrate the feasibility of using this material as a liner for mild steel tubulars to prevent or mitigate corrosion. If successful, the usage of EPDM lined pipe by the geothermal community may have a significant impact on operating costs and serve as a viable alternative to the use of alloyed tubulars. Tooling procedures were developed under this program to mold a 0.64 cm (0.25'') thick Y267 EPDM liner into a tubular test section 61 cm (2') in length and 19.1 cm (7.5'') in diameter (ID). A successful effort was made to identify a potential coupling agent to be used to bond the elastomer to the steel tubular wall. This agent was found to withstand the processing conditions associated with curing the elastomer at 288/sup 0/C and to retain a significant level of adhesive strength following hydrothermal testing in a synthetic brine at 260/sup 0/C for a period of 166 hours. Bonding tests were conducted on specimens of mild carbon steel and several alloys including Hastelloy C-276. An objective of the program was to field test the lined section of pipe mentioned above at a geothermal facility in the Imperial Valley. Though a test was conducted, problems encountered during the lining operation precluded an encouraging outcome. The results of the field demonstration were inconclusive. 6 refs., 13 figs., 13 tabs

  17. Tubular space truss structure for SKITTER 2 robot

    NASA Astrophysics Data System (ADS)

    Beecham, Richard; Dejulio, Linda; Delorme, Paul; Eck, Eric; Levy, Avi; Lowery, Joel; Radack, Joe; Sheffield, Randy; Stevens, Scott

    1988-05-01

    The Skitter 2 is a three legged transport vehicle designed to demonstrate the principle of a tripod walker in a multitude of environments. The tubular truss model of Skitter 2 is a proof of principal design. The model will replicate the operational capabilities of Skitter 2 including its ability to self-right itself. The project's focus was on the use of light weight tubular members in the final structural design. A strong design for the body was required as it will undergo the most intense loading. Triangular geometry was used extensively in the body, providing the required structural integrity and eliminating the need for cumbersome shear panels. Both the basic femur and tibia designs also relied on the strong geometry of the triangle. An intense literature search aided in the development of the most suitable weld techniques, joints, linkages, and materials required for a durable design. The hinge design features the use of spherical rod end bearings. In order to obtain a greater range of mobility in the tibia, a four-bar linkage was designed which attaches both to the femur and the tibia. All component designs, specifically the body, femur, and the tibia were optimized using the software package IDEAS 3.8A Supertab. The package provided essential deformation and stress analysis information on each component's design. The final structure incurred only a 0.0544 inch deflection in a maximum (worst case) loading situation. The highest stress experienced by any AL6061-T6 tubular member was 1920 psi. The structural integrity of the final design facilitated the use of Aluminum 6061-T6 tubing. The tubular truss structure of Skitter 2 is an effective and highly durable design. All facets of the design are structurally sound and cost effective.

  18. A permanent magnet tubular linear generator for wave energy conversion

    NASA Astrophysics Data System (ADS)

    Yu, Haitao; Liu, Chunyuan; Yuan, Bang; Hu, Minqiang; Huang, Lei; Zhou, Shigui

    2012-04-01

    A novel three-phase permanent magnet tubular linear generator (PMTLG) with Halbach array is proposed for the sea wave energy conversion. Non-linear axi-symmetrical finite element method (FEM) is implemented to calculate the magnetic fields along air-gap for different Halbach arrays of PMTLGs. The PMTLG characteristics are analyzed and the simulation results are validated by the experiment. An assistant tooth is implemented to greatly minimize the end and cogging effects which cause the oscillatory detent force.

  19. Tubular biomarkers to assess progression of diabetic nephropathy.

    PubMed

    Tramonti, Gianfranco; Kanwar, Yashpal S

    2011-05-01

    Despite aggressive management, many patients with diabetic nephropathy still develop end-stage renal disease. Accompanying tubulointerstitial damage is important in the progression of diabetic nephropathy. Markers of tubular damage, such as NGAL, KIM-1, and LFABP, have been proposed for monitoring the effectiveness of therapy. However, Nielsen et al. report a lack of an independent correlation between these biomarkers and glomerular filtration rate. Therefore, these markers seem to offer no improvement in the management of diabetic nephropathy. PMID:21527942

  20. Tissue cell assisted fabrication of tubular catalytic platinum microengines

    NASA Astrophysics Data System (ADS)

    Wang, Hong; Moo, James Guo Sheng; Pumera, Martin

    2014-09-01

    We report a facile platform for mass production of robust self-propelled tubular microengines. Tissue cells extracted from fruits of banana and apple, Musa acuminata and Malus domestica, are used as the support on which a thin platinum film is deposited by means of physical vapor deposition. Upon sonication of the cells/Pt-coated substrate in water, microscrolls of highly uniform sizes are spontaneously formed. Tubular microengines fabricated with the fruit cell assisted method exhibit a fast motion of ~100 bodylengths per s (~1 mm s-1). An extremely simple and affordable platform for mass production of the micromotors is crucial for the envisioned swarms of thousands and millions of autonomous micromotors performing biomedical and environmental remediation tasks.We report a facile platform for mass production of robust self-propelled tubular microengines. Tissue cells extracted from fruits of banana and apple, Musa acuminata and Malus domestica, are used as the support on which a thin platinum film is deposited by means of physical vapor deposition. Upon sonication of the cells/Pt-coated substrate in water, microscrolls of highly uniform sizes are spontaneously formed. Tubular microengines fabricated with the fruit cell assisted method exhibit a fast motion of ~100 bodylengths per s (~1 mm s-1). An extremely simple and affordable platform for mass production of the micromotors is crucial for the envisioned swarms of thousands and millions of autonomous micromotors performing biomedical and environmental remediation tasks. Electronic supplementary information (ESI) available: Related video. See DOI: 10.1039/c4nr03720k

  1. Acute Kidney Injury.

    PubMed

    Zuk, Anna; Bonventre, Joseph V

    2016-01-01

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

  2. Renal Papillary Necrosis Caused by Protein C Deficiency Leading to Recurrent Hydronephrosis

    PubMed Central

    Olorunnisomo, Vincent; Fowle, Evan James; Modica, Ippolito; Meisels, Ira; Gupta, Mantu

    2016-01-01

    Abstract A patient with history of a solitary functioning kidney and protein C deficiency (PCD) presented with recurrent severe hydronephrosis causing acute kidney injury upon chronic kidney disease. Work-up with endoscopic evaluation revealed renal papillary necrosis (RPN) and sloughed renal papillae to be the true cause of the recurrent obstruction. Pathologic evaluation of the sloughed tissue confirmed the diagnosis of RPN. This is the first case reported in the literature illustrating the unique presentation of RPN in the setting of PCD. PMID:27579411

  3. Renal Papillary Necrosis Caused by Protein C Deficiency Leading to Recurrent Hydronephrosis.

    PubMed

    Chugh, Rohit Kumar; Olorunnisomo, Vincent; Fowle, Evan James; Modica, Ippolito; Meisels, Ira; Gupta, Mantu

    2016-01-01

    A patient with history of a solitary functioning kidney and protein C deficiency (PCD) presented with recurrent severe hydronephrosis causing acute kidney injury upon chronic kidney disease. Work-up with endoscopic evaluation revealed renal papillary necrosis (RPN) and sloughed renal papillae to be the true cause of the recurrent obstruction. Pathologic evaluation of the sloughed tissue confirmed the diagnosis of RPN. This is the first case reported in the literature illustrating the unique presentation of RPN in the setting of PCD. PMID:27579411

  4. Acute renal failure following oxalic acid poisoning: a case report

    PubMed Central

    2012-01-01

    Oxalic acid poisoning is being recognized as an emerging epidemic in the rural communities of Sri Lanka as it is a component of locally produced household laundry detergents. Herein we describe a case of a 32 year old female, presenting after direct ingestion of oxalic acid. She then went on to develop significant metabolic acidosis and acute renal failure, requiring dialysis. Renal biopsy revealed acute tubulointerstitial nephritis associated with diffuse moderate acute tubular damage with refractile crystals in some of the tubules. The patient symptomatically improved with haemodialysis and renal functions subsequently returned to normal. PMID:22978510

  5. Pediatric Tubular Pulmonary Heart Valve from Decellularized Engineered Tissue Tubes

    PubMed Central

    Reimer, Jay M.; Syedain, Zeeshan H.; Haynie, Bee H.T.; Tranquillo, Robert T.

    2015-01-01

    Pediatric patients account for a small portion of the heart valve replacements performed, but a pediatric pulmonary valve replacement with growth potential remains an unmet clinical need. Herein we report the first tubular heart valve made from two decellularized, engineered tissue tubes attached with absorbable sutures, which can meet this need, in principle. Engineered tissue tubes were fabricated by allowing ovine dermal fibroblasts to replace a sacrificial fibrin gel with an aligned, cell-produced collagenous matrix, which was subsequently decellularized. Previously, these engineered tubes became extensively recellularized following implantation into the sheep femoral artery. Thus, a tubular valve made from these tubes may be amenable to recellularization and, ideally, somatic growth. The suture line pattern generated three equi-spaced “leaflets” in the inner tube, which collapsed inward when exposed to back pressure, per tubular valve design. Valve testing was performed in a pulse duplicator system equipped with a secondary flow loop to allow for root distention. All tissue-engineered valves exhibited full leaflet opening and closing, minimal regurgitation (< 5%), and low systolic pressure gradients (< 2.5 mmHg) under pulmonary conditions. Valve performance was maintained under various trans-root pressure gradients and no tissue damage was evident after 2 million cycles of fatigue testing. PMID:26036175

  6. Gage for measuring fluted oil field tubular members

    SciTech Connect

    Case, W.A.; Burt, J.R.

    1987-03-17

    A gage is described for measuring the nominal diameter of an elongated tubular member having circumferentially spaced apart radially outwardly extending flutes and for calibrating the amount of wear to the flutes and predicting the future wear life of the tubular member. The gage comprises: a first gage part including a pair of spaced apart colinear elongated first handlebar halves with a generally semi-circular first half ring positioned between the first handlebar halves. The first half ring includes at least one flute engaging surface which includes stepped arcuate flute engaging portions positioned at radii from the center of the first ring half corresponding to different diameters to be measured; a second gage part including a pair of spaced apart colinear elongated second handlebar halves with a generally semicircular second half ring positioned between the second handlebar halves. The second half ring includes at least one flute engaging surface which includes stepped arcuate flute engaging portions positioned a radii from the center of the second ring half corresponding to different diameters to be measured. The number of flute engaging surfaces of the first and second ring halves is equal to the number of flutes on the tubular member; and a hinge pivotally connecting together one handlebar half of the first gage part to one handlebar half of the second gage part.

  7. Band gap in tubular pillar phononic crystal plate.

    PubMed

    Shu, Fengfeng; Liu, Yongshun; Wu, Junfeng; Wu, Yihui

    2016-09-01

    In this paper, a phononic crystal (PC) plate with tubular pillars is presented and investigated. The band structures and mode displacement profiles are calculated by using finite element method. The result shows that a complete band gap opens when the ratio of the pillar height to the plate thickness is about 1.6. However, for classic cylinder pillar structures, a band gap opens when the ratio is equal or greater than 3. A tubular pillar design with a void room in it enhances acoustic multiple scattering and gives rise to the opening of the band gap. In order to verify it, a PC structure with double tubular pillars different in size (one within the other) is introduced and a more than 2times band gap enlargement is observed. Furthermore, the coupling between the resonant mode and the plate mode around the band gap is characterized, as well as the effect of the geometrical parameters on the band gap. The behavior of such structure could be utilized to design a pillar PC with stronger structural stability and to enlarge band gaps. PMID:27376841

  8. A Tubular Biomaterial Construct Exhibiting a Negative Poisson's Ratio.

    PubMed

    Lee, Jin Woo; Soman, Pranav; Park, Jeong Hun; Chen, Shaochen; Cho, Dong-Woo

    2016-01-01

    Developing functional small-diameter vascular grafts is an important objective in tissue engineering research. In this study, we address the problem of compliance mismatch by designing and developing a 3D tubular construct that has a negative Poisson's ratio νxy (NPR). NPR constructs have the unique ability to expand transversely when pulled axially, thereby resulting in a highly-compliant tubular construct. In this work, we used projection stereolithography to 3D-print a planar NPR sheet composed of photosensitive poly(ethylene) glycol diacrylate biomaterial. We used a step-lithography exposure and a stitch process to scale up the projection printing process, and used the cut-missing rib unit design to develop a centimeter-scale NPR sheet, which was rolled up to form a tubular construct. The constructs had Poisson's ratios of -0.6 ≤ νxy ≤ -0.1. The NPR construct also supports higher cellular adhesion than does the construct that has positive νxy. Our NPR design offers a significant advance in the development of highly-compliant vascular grafts. PMID:27232181

  9. Helium permeation through a silicalite-1 tubular membrane

    NASA Astrophysics Data System (ADS)

    Hernández, M. G.; Salinas-Rodríguez, E.; Gómez, S. A.; Roa-Neri, J. A. E.; Alfaro, S.; Valdés-Parada, F. J.

    2015-06-01

    A silicalite-1 tubular membrane was prepared on the inner surface of a porous α-alumina support. Helium permeation at different feed volumetric flows (11-41 mL/min) with different sweep flow rates (9-90 mL/min) at STP conditions was measured. The molar fraction was obtained as a function of the residence time ratio. The influences of the geometric parameters of the tubular system and the feed flow rates on the permeation through the membrane were investigated. The dependence of the permeances with the residence time ratio was experimentally obtained and we propose that this dependence is a useful design criterion for tubular membrane permeation systems. The best results in this work were obtained for Q He, in / Q N2, in = 0.22 for V SS / V TS = 7.3. Also, the data showed that an appropriate combination of the flows and the area sections of the system resulted in an optimum value for the Péclet number of 0.3. The experimental data were reproduced by numerically solving the Maxwell-Stefan equations under the assumption that transport across the membrane can be modeled in terms of a Robin-type boundary condition.

  10. Developmental changes in renal tubular transport-an overview.

    PubMed

    Gattineni, Jyothsna; Baum, Michel

    2015-12-01

    The adult kidney maintains a constant volume and composition of extracellular fluid despite changes in water and salt intake. The neonate is born with a kidney that has a small fraction of the glomerular filtration rate of the adult and immature tubules that function at a lower capacity than that of the mature animal. Nonetheless, the neonate is also able to maintain a constant extracellular fluid volume and composition. Postnatal renal tubular development was once thought to be due to an increase in the transporter abundance to meet the developmental increase in glomerular filtration rate. However, postnatal renal development of each nephron segment is quite complex. There are isoform changes of several transporters as well as developmental changes in signal transduction that affect the capacity of renal tubules to reabsorb solutes and water. This review will discuss neonatal tubular function with an emphasis on the differences that have been found between the neonate and adult. We will also discuss some of the factors that are responsible for the maturational changes in tubular transport that occur during postnatal renal development. PMID:24253590

  11. Method and apparatus for forming flues on tubular stock

    DOEpatents

    Beck, D.E.; Carson, C.

    1979-12-21

    The present invention is directed to a die mechanism utilized for forming flues on long, relatively narrow tubular stock. These flues are formed by displacing a die from within the tubular stock through perforations previously drilled through the tubular stock at selected locations. The drawing of the die upsets the material to form the flue of the desired configuration. The die is provided with a lubricating system which enables the lubricant to be dispensed uniformly about the entire periphery of the die in contact with the material being upset so as to assure the formation of the flues. Further, the lubricant is dispensed from within the die onto the peripheral surface of the latter at pressures in the range of about 2000 to 10,000 psi so as to assure the adequate lubrication of the die during the drawing operation. By injecting the lubricant at such high pressures, low viscosity liquid, such as water and/or alcohol, may be efficiently used as a lubricant and also provides a mechanism by which the lubricant may be evaporated from the surface of the flues at ambient conditions so as to negate the cleansing operations previously required prior to joining the flues to other conduit mechanisms by fusion welding and the like.

  12. The rebirth of interest in renal tubular function.

    PubMed

    Lowenstein, Jerome; Grantham, Jared J

    2016-06-01

    The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. PMID:26936872

  13. Tubular transport and metabolism of cimetidine in chicken kidneys

    SciTech Connect

    Rennick, B.; Ziemniak, J.; Smith, I.; Taylor, M.; Acara, M.

    1984-02-01

    Renal tubular transport and renal metabolism of (/sup 14/C)cimetidine (CIM) were investigated by unilateral infusion into the renal portal circulation in chickens (Sperber technique). (/sup 14/C)CIM was actively transported at a rate 88% that of simultaneously infused p-aminohippuric acid, and its transport was saturable. The following organic cations competitively inhibited the tubular transport of (/sup 14/C)CIM with decreasing potency: CIM, ranitidine, thiamine, procainamide, guanidine and choline. CIM inhibited the transport of (/sup 14/C)thiamine, (/sup 14/C)amiloride and (/sup 14/C)tetraethylammonium. During CIM infusion, two renal metabolites, CIM sulfoxide and hydroxymethylcimetidine, were found in urine. When CIM sulfoxide was infused, its transport efficiency was 32% and not saturable. CIM sulfoxide did ot inhibit the simultaneous renal tubular transport of p-aminohippuric acid or tetraethylammonium. CIM is transported by the organic cation transport system and the kidney metabolizes CIM. Transport of CIM and other cationic drugs could produce a drug interaction to alter drug excretion.

  14. HCaRG Accelerates Tubular Repair after Ischemic Kidney Injury

    PubMed Central

    Matsuda, Hiroyuki; Lavoie, Julie L.; Gaboury, Louis; Hamet, Pavel

    2011-01-01

    The repair of the kidney after ischemia/reperfusion injury involves proliferation of proximal tubular epithelial cells as well as cell migration and differentiation. Immediately after reperfusion, expression of hypertension-related calcium-regulated gene (HCaRG/COMMD5) decreases, but its expression increases even higher than baseline during repair. HCaRG inhibits proliferation and accelerates wound healing and differentiation in cultured cells, but whether HCaRG can stimulate renal repair after ischemia/reperfusion injury is unknown. Here, transgenic mice overexpressing human HCaRG survived longer and recovered renal function faster than littermate controls after ischemia/reperfusion (64% versus 25% survival at 7 days). Proliferation of proximal tubular epithelial cells stopped earlier after ischemia/reperfusion injury, E-cadherin levels recovered more rapidly, and vimentin induction abated faster in transgenic mice. HCaRG overexpression also reduced macrophage infiltration and inflammation after injury. Taken together, these data suggest that HCaRG accelerates repair of renal proximal tubules by modulating cell proliferation of resident tubular epithelial cells and by facilitating redifferentiation. PMID:21921141

  15. Acute pyelonephritis can have serious complications.

    PubMed

    Shields, Joanne; Maxwell, Alexander P

    2010-04-01

    Urinary tract infection (UTI) may predominantly involve the lower urinary tract, i.e. acute cystitis, or upper urinary tract consisting of the renal pelvis and kidney,, i.e. acute pyelonephritis The incidence of acute pyelonephritis is higher in young women than in men but the incidence in men over 65 is similar to that in older women. Women have up to a 10% risk of recurrent acute pyelonephritis in the year following a first acute episode. The equivalent risk in men is 6%. Acute pyelonephritis may be uncomplicated and resolve without serious sequelae. A minority of episodes may be complicated by acute kidney injury, papillary necrosis, renal or perinephric abscess or the development of emphysematous pyelonephritis. Acute pyelonephritis is generally caused by microorganisms ascending from the urethra via the bladder into the upper urinary tract. Rarely the kidney may be seeded by blood-borne infection. Ecoli is the most common uropathogen causing pyelonephritis accounting for 70-90% of infections. Species of Enterococci, Klebsiella, Pseudomonas, Proteus and Staphylococci are responsible for the remaining infections. There is a rising incidence in the community of UTI with bacteria that produce extended spectrum beta-lactamase (ESBL) enzymes. These ESBL bacteria have developed resistance to antibiotics such as penicillin, cephalosporins and increasingly to quinolones. Risk factors for uncomplicated acute pyelonephritis include recent sexual intercourse, acute cystitis, stress incontinence and diabetes and for complicated acute pyelonephritis include pregnancy, diabetes, anatomical abnormalities of the urinary tract and renal calculi. PMID:20486480

  16. Multiorgan dysfunction syndrome secondary to joint supplement overdosage in a dog

    PubMed Central

    Nobles, Irma J.; Khan, Safdar

    2015-01-01

    A 5-year-old spayed female Bernese mountain dog, with a chief complaint of vomiting and melena ingested approximately 200 nutritional joint supplement tablets. Despite aggressive therapy, the patient developed a coagulopathy, pancreatitis, peritonitis, acute kidney injury, and was euthanized. Postmortem examination revealed myocardial necrosis, pneumonia, centrilobular hemorrhage and necrosis of the liver, vasculitis, and acute tubular necrosis. PMID:25829554

  17. Multiorgan dysfunction syndrome secondary to joint supplement overdosage in a dog.

    PubMed

    Nobles, Irma J; Khan, Safdar

    2015-04-01

    A 5-year-old spayed female Bernese mountain dog, with a chief complaint of vomiting and melena ingested approximately 200 nutritional joint supplement tablets. Despite aggressive therapy, the patient developed a coagulopathy, pancreatitis, peritonitis, acute kidney injury, and was euthanized. Postmortem examination revealed myocardial necrosis, pneumonia, centrilobular hemorrhage and necrosis of the liver, vasculitis, and acute tubular necrosis. PMID:25829554

  18. A steroid-induced bilateral avascular necrosis of the femoral head in an underage patient affected by multiple sclerosis

    PubMed Central

    Carulli, Christian; Nistri, Lorenzo; Bracco, Laura; Giannini, Marta; Amato, Maria Pia

    2015-01-01

    Summary Patients affected by Multiple Sclerosis are often treated by pulsed intravenous corticosteroids to manage acute relapses with positive outcomes. The intravenous administration is frequently associated to avascular necrosis of several bones, particularly the femur. The present report regards a case of an underage MS patient with a bilateral ANFH secondary to pulsed administrations of steroids, managed by a conservative approach on a hip, and by a novel surgical technique on the contralateral side. PMID:26811707

  19. A steroid-induced bilateral avascular necrosis of the femoral head in an underage patient affected by multiple sclerosis.

    PubMed

    Carulli, Christian; Nistri, Lorenzo; Bracco, Laura; Giannini, Marta; Amato, Maria Pia

    2015-01-01

    Patients affected by Multiple Sclerosis are often treated by pulsed intravenous corticosteroids to manage acute relapses with positive outcomes. The intravenous administration is frequently associated to avascular necrosis of several bones, particularly the femur. The present report regards a case of an underage MS patient with a bilateral ANFH secondary to pulsed administrations of steroids, managed by a conservative approach on a hip, and by a novel surgical technique on the contralateral side. PMID:26811707

  20. The Pathology of Acute Liver Failure.

    PubMed

    Lefkowitch, Jay H

    2016-05-01

    Acute liver failure (ALF) is a rare and severe liver disease that usually develops in 8 weeks or less in individuals without preexisting liver disease. Its chief causes worldwide are hepatitis virus infections (hepatitis A, B, and E) and drug hepatotoxicity (particularly intentional or unintentional acetaminophen toxicity). Massive hepatic necrosis is often seen in liver specimens in ALF and features marked loss of hepatocytes, variable degrees of inflammation, and a stereotypic proliferation of bile ductular structures (neocholangioles) derived from activated periportal hepatic progenitor cells. This paper reviews the liver pathology in ALF, including forms of zonal necrosis and their etiologies. PMID:27058243

  1. Acute Pancreatitis Classifications: Basis and Key Goals.

    PubMed

    Xu, Xiao Dong; Wang, Zhe Yuan; Zhang, Ling Yi; Ni, Rui; Wei, Feng Xian; Han, Wei; Zhang, Hui Han; Zhang, Ya Wu; Wei, Zhen Gang; Guo, Xiao Hu; Guo, Liu Qiang; Ma, Jian Zhong; Zhang, You Cheng

    2015-12-01

    To explore the efficacy of the revised Atlanta classification (RACAP) and the determinant-based classification of acute pancreatitis severity (DBCAPS) on the basis of clinical data and feedback from patients with acute pancreatitis (AP). The authors retrospectively investigated a total of 573 patients with AP admitted to our hospital between December 2011 and December 2014. The definitions of severity and local complications in AP using RACAP and DBCAPS are presented and common points and mutual differences between the 2 groups are analyzed and discussed. Classification according to RACAP and DBCAPS found 86 (15%) and 178 (31.1%) mild cases (P < 0.01), 269 (46.9%) and 176 (30.7%) moderate cases (P < 0.01), and 218 (38.0%) and 219 (38.2%) severe cases (P = 0.95), respectively. A major contribution of DBCAPS is the introduction of a new type of severe AP, critical AP, identified in 4 patients (0.7%). Complications were observed in 313 RACAP-defined cases and 153 DBCAPS-defined cases (P < 0.01). Among the 313 RACAP-defined cases, acute peripancreatic fluid collection (236 patients, 75.40%), pancreatic pseudocysts (20 patients, 6.4%), acute necrotic collection (42 patients, 13.4%), and walled-off necrosis (15 patients, 4.8%) were observed. Among the 153 DBCAPS-defined cases, sterile peripancreatic necrosis (105 patients, 68.6%), sterile pancreatic necrosis (44 patients, 28.8%), infected peripancreatic necrosis (2 patients, 1.3%), and infected pancreatic necrosis (2/153 patients, 1.3%) were observed. Both classifications adopted organ failure and complications as determinants of severity. Revised Atlanta classification refined local complications and DBCAPS modified severity to include critical AP. In accordance with the demands of precision medicine, a combination of the 2 could be important for further clinical practice and scientific research. PMID:26632905

  2. Pretreatment by low-dose fibrates protects against acute free fatty acid-induced renal tubule toxicity by counteracting PPAR{alpha} deterioration

    SciTech Connect

    Takahashi, Kyoko; Kamijo, Yuji; Hora, Kazuhiko; Hashimoto, Koji; Higuchi, Makoto; Nakajima, Takero; Ehara, Takashi; Shigematsu, Hidekazu; Gonzalez, Frank J.; Aoyama, Toshifumi

    2011-05-01

    Development of a preventive strategy against tubular damage associated with proteinuria is of great importance. Recently, free fatty acid (FFA) toxicities accompanying proteinuria were found to be a main cause of tubular damage, which was aggravated by insufficiency of peroxisome proliferator-activated receptor alpha (PPAR{alpha}), suggesting the benefit of PPAR{alpha} activation. However, an earlier study using a murine acute tubular injury model, FFA-overload nephropathy, demonstrated that high-dose treatment of PPAR{alpha} agonist (0.5% clofibrate diet) aggravated the tubular damage as a consequence of excess serum accumulation of clofibrate metabolites due to decreased kidney elimination. To induce the renoprotective effects of PPAR{alpha} agonists without drug accumulation, we tried a pretreatment study using low-dose clofibrate (0.1% clofibrate diet) using the same murine model. Low-dose clofibrate pretreatment prevented acute tubular injuries without accumulation of its metabolites. The tubular protective effects appeared to be associated with the counteraction of PPAR{alpha} deterioration, resulting in the decrease of FFAs influx to the kidney, maintenance of fatty acid oxidation, diminution of intracellular accumulation of undigested FFAs, and attenuation of disease developmental factors including oxidative stress, apoptosis, and NF{kappa}B activation. These effects are common to other fibrates and dependent on PPAR{alpha} function. Interestingly, however, clofibrate pretreatment also exerted PPAR{alpha}-independent tubular toxicities in PPAR{alpha}-null mice with FFA-overload nephropathy. The favorable properties of fibrates are evident when PPAR{alpha}-dependent tubular protective effects outweigh their PPAR{alpha}-independent tubular toxicities. This delicate balance seems to be easily affected by the drug dose. It will be important to establish the appropriate dosage of fibrates for treatment against kidney disease and to develop a novel PPAR

  3. Centrilobular zonal necrosis as a hallmark of a distinctive subtype of autoimmune hepatitis

    PubMed Central

    Abe, Hiroshi; Sugita, Tomonori; Seki, Nobuyoshi; Chuganji, Yoshimichi; Furumoto, Youhei; Sakata, Akihiko

    2016-01-01

    Background and aim Centrilobular zonal necrosis (CZN) is a known histological variant of autoimmune hepatitis (AIH). However, the significance of CZN is yet to be fully elucidated. This study aimed to determine whether CZN is a hallmark of a distinctive subtype of AIH. Methods Histological changes in the centrilobular zones of liver biopsies from 113 AIH patients were assessed by a single pathologist and classified into three categories: typical zonal necrosis defined as CZN (15 patients); other necroinflammatory change (NIC; 24 patients); and absence of necrosis (non-NIC; 74 patients). The clinicopathological features and immunogenetic background of CZN patients were then assessed. Results The clinicopathological features of AIH with CZN were distinct from other types of AIH, including a higher frequency of acute onset, lower frequency of antinuclear antibodies, lower antinuclear antibody titers, lower serum immunoglobulin G levels, lower grade interface hepatitis, less prominent lymphoplasmacytic infiltration, and lower AIH score. Increased and decreased frequencies of HLA-DR9 and HLA-DR4, respectively, were identified as immunogenetic features of AIH with CZN. Conversely, the clinicopathological characteristics of AIH with NIC were similar to those of non-NIC AIH, including the majority of the AIH patients. The therapeutic outcomes of AIH with CZN were excellent when precise diagnoses were made without delay. Conclusion The clinicopathological features and immunogenetic background of AIH with CZN differed from AIH without CZN. CZN may be a hallmark of a distinct subtype of AIH. PMID:26657454

  4. The interplay between regulated necrosis and bacterial infection.

    PubMed

    Blériot, Camille; Lecuit, Marc

    2016-06-01

    Necrosis has long been considered as a passive event resulting from a cell extrinsic stimulus, such as pathogen infection. Recent advances have refined this view and it is now well established that necrosis is tightly regulated at the cell level. Regulated necrosis can occur in the context of host-pathogen interactions, and can either participate in the control of infection or favor it. Here, we review the two main pathways implicated so far in bacteria-associated regulated necrosis: caspase 1-dependent pyroptosis and RIPK1/RIPK3-dependent necroptosis. We present how these pathways are modulated in the context of infection by a series of model bacterial pathogens. PMID:27048818

  5. Tumour necrosis factor production in Falciparum malaria and its association with schizont rupture.

    PubMed Central

    Kwiatkowski, D; Cannon, J G; Manogue, K R; Cerami, A; Dinarello, C A; Greenwood, B M

    1989-01-01

    To investigate the involvement of tumour necrosis factor (TNF) in human malaria, we studied TNF production in patients infected with Plasmodium falciparum, and in co-cultures of human mononuclear cells and malaria parasites in vitro. In the examined sample, plasma TNF levels of over 39 pg/ml were detected in the plasma of 59% of Gambian children with acute malaria, 17% of convalescents, 9% of children with mild infections other than malaria, and 7% of healthy Gambian adults. Mononuclear cells of acute malaria patients, when stimulated with endotoxin in vitro, secreted twice as much TNF as did those of convalescent individuals, and three times that of healthy adult controls. Erythrocytic cultures of P. falciparum stimulated increased TNF secretion by mononuclear cells from uninfected individuals, and a sharp rise in the rate of secretion occurred shortly after schizont rupture. We suggest that malaria fever is mediated, at least in part, through paroxysmal TNF release associated with schizont rupture. PMID:2680183

  6. Modulation of Endogenous Hormone Action by Recombinant Human Tumor Necrosis Factor

    NASA Astrophysics Data System (ADS)

    Warren, Robert S.; Donner, David B.; Fletcher Starnes, H.; Brennan, Murray F.

    1987-12-01

    Tumor necrosis factor (TNF) has been implicated in the toxic manifestations of overwhelming bacterial infection and in the tissue wasting that often accompanies prolonged infections and malignancy. We have examined a possible role of TNF in the early metabolic alterations following acute tissue injury or sepsis. Recombinant human TNF stimulated rat liver amino acid uptake up to 5-fold in vivo and there was a concomitant increase in plasma glucagon. In vitro TNF had no direct effect on hepatocyte amino acid uptake, but it markedly enhanced the stimulation of amino acid transport by glucagon, without an alteration in binding of glucagon to hepatocytes. This permissive effect of TNF on glucagon action represents an interrelationship between the immune and endocrine systems, and it may help to explain the mechanism of hormonal regulation of both the anabolic and catabolic responses to acute injury.

  7. The restrained expression of NF-kB in renal tissue ameliorates folic acid induced acute kidney injury in mice.

    PubMed

    Kumar, Dev; Singla, Surinder K; Puri, Veena; Puri, Sanjeev

    2015-01-01

    The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI. PMID:25559736

  8. The Restrained Expression of NF-kB in Renal Tissue Ameliorates Folic Acid Induced Acute Kidney Injury in Mice

    PubMed Central

    Kumar, Dev; Singla, Surinder K.; Puri, Veena; Puri, Sanjeev

    2015-01-01

    The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI. PMID:25559736

  9. Adjudication of etiology of acute kidney injury: experience from the TRIBE-AKI multi-center study

    PubMed Central

    2014-01-01

    Background Adjudication of patient outcomes is a common practice in medical research and clinical trials. However minimal data exists on the adjudication process in the setting of Acute Kidney Injury (AKI) as well as the ability to judge different etiologies (e.g. Acute Tubular Necrosis (ATN), Pre-renal Azotemia (PRA)). Methods We enrolled 475 consecutive patients undergoing cardiac surgery at four sites of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) study. Three expert nephrologists performed independent chart review, utilizing clinical variables and retrospective case report forms with pre intra and post-operative data, and then adjudicated all cases of AKI (n = 67). AKI was defined as a > 50% increase in serum creatinine for baseline (RIFLE Risk). We examined the patterns of AKI diagnoses made by the adjudication panel as well as association of these diagnoses with pre and postoperative kidney injury biomarkers. Results There was poor agreement across the panel of reviewers with their adjudicated diagnoses being independent of each other (Fleiss’ Kappa = 0.046). Based on the agreement of the two out of three reviewers, ATN was the adjudicated diagnosis in 41 cases (61%) while PRA occurred in 13 (19%). Neither serum creatinine or any other biomarker of AKI (urine or serum), was associated with an adjudicated diagnosis of ATN within the first 24 post-operative hours. Conclusion The etiology of AKI after cardiac surgery is probably multi-factorial and pure forms of AKI etiologies, such as ATN and PRA may not exist. Biomarkers did not appear to correlate with the adjudicated etiology of AKI; however the lack of agreement among the adjudicators impacted these results. Trial registration Clinicaltrials.gov: NCT00774137 PMID:24996668

  10. Effect of granulocyte colony-stimulating factor administration on renal regeneration after experimentally induced acute kidney injury in dogs.

    PubMed

    Lim, Chae-Young; Han, Jae-Ik; Kim, Seung-Gon; Lee, Chang-Min; Park, Hee-Myung

    2016-02-01

    OBJECTIVE To evaluate the effects of granulocyte colony-stimulating factor (GCSF) administration in dogs with experimentally induced acute kidney injury. ANIMALS 6 healthy dogs. PROCEDURES After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), the dogs were randomly assigned into 2 groups (n = 3 dogs/group). Then dogs immediately received GCSF (10 μg/kg) or 1 mL of saline (0.9% NaCl) solution (control group) SC; this treatment was repeated once daily for 4 additional days (days 1 through 4). A once-daily CBC (day 0 to 4), serum biochemical analysis (day 0 to 3), and urinalysis (day 0 to 3) were performed for each dog; samples were collected before administration of cisplatin (day 0) and before treatment with GCSF or saline solution (days 1 through 4). After sample collection and treatment on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analyses, and cytokine profiling via reverse transcriptase PCR assay. RESULTS In the GCSF-treated group, the histologic evaluation and immunohistochemical analyses of kidney tissue revealed less fibrotic change and greater proliferation of renal tubular epithelial cells, compared with findings in the control group. The mRNA profiles of kidney tissue from the GCSF-treated group indicated lower expression of tumor necrosis factor-α and tumor growth factor-β, compared with findings in the control group; however, concentrations of factors related to renal regeneration were not greater in the GCSF-treated group. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that GCSF treatment can impede renal fibrosis and increase proliferation of renal tubules after experimentally induced acute kidney injury in dogs. (Am J Vet Res 2016;77:199-207). PMID:27027715

  11. Mitochondria-targeted antioxidants do not prevent tumour necrosis factor-induced necrosis of L929 cells.

    PubMed

    Jarvis, Reagan M; Göttert, Jana; Murphy, Michael P; Ledgerwood, Elizabeth C

    2007-09-01

    Mitochondrial production of reactive oxygen species (ROS) is widely reported as a central effector during TNF-induced necrosis. The effect of a family of mitochondria-targeted antioxidants on TNF-induced necrosis of L929 cells was studied. While the commonly used lipid-soluble antioxidant BHA effectively protected cells from TNF-induced necrosis, the mitochondria-targeted antioxidants MitoQ(3), MitoQ(5), MitoQ(10) and MitoPBN had no effect on TNF-induced necrosis. Since BHA also acts as an uncoupler of mitochondrial membrane potential, two additional uncouplers were tested. FCCP and CCCP both provided dose-dependent inhibition of TNF-induced necrosis. In conclusion, the generation of mitochondrial ROS may not be necessary for TNF-induced necrosis. Instead, these results suggest alternative mitochondrial functions, such as a respiration-dependent process, are critical for necrotic death. PMID:17729122

  12. Severe Hepatic Necrosis Associated with Methyldopa

    PubMed Central

    Cameron, Ian A.; Achord, James L.; Bartee, Harry

    1981-01-01

    Family physicians should carefully follow their patients receiving methyldopa for liver toxicity. Methyldopa is commonly used in treating hypertension and its hepatotoxic potential is frequently overlooked. This point is illustrated in the following case report involving a 45-year-old black female. The patient had been receiving oral methyldopa for 7.5 months prior to hospitalization for control of severe hypertension. Methyldopa was discontinued on her second hospital day when her liver tests were found to be abnormal. She developed progressive liver failure and lapsed into hepatic coma. Subsequently, her liver biopsy showed severe hepatic necrosis. She slowly improved with medical management. Her liver tests returned to normal; she resumed work and at 14 months follow up her liver biopsy showed no evidence of chronic active liver disease. Monitoring for methyldopa toxicity as outlined in this article could have prevented this costly and near lethal side effect. ImagesFig. 1Fig. 2 PMID:21289717

  13. Eosinophilic Gastritis Presenting as Tissue Necrosis

    PubMed Central

    Jo, Yong Min; Jang, Jin Seok; Han, Seung Hee; Kang, Sang Hyun; Kim, Woo Jae; Jeong, Jin Sook

    2015-01-01

    Eosinophilic gastroenteritis is very rare disorder that is characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of any definite causes of eosinophilia. It is associated with various clinical gastrointestinal manifestations, and depends on the involved layer and site. We report a case of eosinophilic gastritis presenting with severe necrosis. The symptoms disappeared immediately after beginning steroid treatment, and the eosinophil count decreased to the reference range. The patient showed eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis. It is a unique presentation of eosinophilic gastritis. To the best of our knowledge, no case of eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis has been previously reported in Korea. PMID:26668805

  14. The molecular interactions between filtered proteins and proximal tubular cells in proteinuria.

    PubMed

    Baines, Richard J; Brunskill, Nigel J

    2008-01-01

    Proteinuria is associated with progressive chronic kidney disease and poor cardiovascular outcomes. Exposure of proximal tubular epithelial cells to excess proteins leads to the development of proteinuric nephropathy with tubular atrophy, interstitial inflammation and scarring. Numerous signalling pathways are activated in proximal tubular epithelial cells under proteinuric conditions resulting in gene transcription, altered growth and the secretion of inflammatory and profibrotic mediators. Megalin, the proximal tubular scavenger receptor for filtered macromolecules, has intrinsic signalling functions and may also link albumin to growth factor receptor signalling via regulated intramembrane proteolysis. It now seems that endocytosis is not always a prerequisite for albumin-evoked alterations in proximal tubular cell phenotype. Recent evidence shows the presence of other potential receptors for proteins, such as the neonatal Fc receptor and CD36, in the proximal tubular epithelium. PMID:18849618

  15. Isolation of Leptospira from a phocid: acute renal failure and mortality from Leptospirosis in rehabilitated northern elephant seals (Mirounga angustirostris), California, USA.

    PubMed

    Delaney, Martha A; Colegrove, Kathleen M; Spraker, Terry R; Zuerner, Richard L; Galloway, Renee L; Gulland, Frances M D

    2014-07-01

    During rehabilitation, acute renal failure due to leptospirosis occurred in eight male northern elephant seals (Mirounga angustirostris) that stranded along the central California coast in 2011. Characteristic histologic lesions including renal tubular degeneration, necrosis, and mineralization, and mild lymphoplasmacytic interstitial nephritis were noted in the six animals examined. Immunohistochemistry, bacterial culture, and PCR were positive in 2/3, 2/3, and 3/4 seals, respectively, and 6/8 had high serum antibody titers to Leptospira interrogans serovar pomona. Pulsed-field gel electrophoresis confirmed one isolate as serovar pomona. Variable number tandem repeat (VNTR) analysis showed both elephant seal isolates were identical to each other but distinct from those isolated from California sea lions (Zalophus californianus). The time from stranding to onset of azotemia was 1 to 38 (median=24) days, suggesting some seals were infected at the rehabilitation facility. Based on temporal and spatial incidence of infection, transmission among elephant seals likely occurred during rehabilitation. Molecular (VNTR) analysis of the two isolates indicates there is a unique L. interrogans serovar pomona genotype in elephant seals, and sea lions were not the source of infection prior to or during rehabilitation. This study confirms the susceptibility of northern elephant seals to leptospirosis, indicates intraspecies transmission during rehabilitation, and reports the first isolation and preliminary characterization of leptospires from elephant seals. PMID:24807176

  16. TNFα Amplifies DNaseI Expression in Renal Tubular Cells while IL-1β Promotes Nuclear DNaseI Translocation in an Endonuclease-Inactive Form

    PubMed Central

    Thiyagarajan, Dhivya; Rekvig, Ole Petter; Seredkina, Natalya

    2015-01-01

    We have demonstrated that the renal endonuclease DNaseI is up-regulated in mesangial nephritis while down-regulated during progression of the disease. To determine the basis for these reciprocal DNaseI expression profiles we analyse processes accounting for an early increase in renal DNaseI expression. Main hypotheses were that i. the mesangial inflammation and secreted pro-inflammatory cytokines directly increase DNaseI protein expression in tubular cells, ii. the anti-apoptotic protein tumor necrosis factor receptor-associated protein 1 (Trap 1) is down-regulated by increased expression of DNaseI due to transcriptional interference, and iii. pro-inflammatory cytokines promote nuclear translocation of a variant of DNaseI. The latter hypothesis emerges from the fact that anti-DNaseI antibodies stained tubular cell nuclei in murine and human lupus nephritis. The present study was performed on human tubular epithelial cells stimulated with pro-inflammatory cytokines. Expression of the DNaseI and Trap 1 genes was determined by qPCR, confocal microscopy, gel zymography, western blot and by immune electron microscopy. Results from in vitro cell culture experiments were analysed for biological relevance in kidneys from (NZBxNZW)F1 mice and human patients with lupus nephritis. Central data indicate that stimulating the tubular cells with TNFα promoted increased DNaseI and reduced Trap 1 expression, while TNFα and IL-1β stimulation induced nuclear translocation of the DNaseI. TNFα-stimulation resulted in 3 distinct effects; increased DNaseI and IL-1β gene expression, and nuclear translocation of DNaseI. IL-1β-stimulation solely induced nuclear DNaseI translocation. Tubular cells stimulated with TNFα and simultaneously transfected with IL-1β siRNA resulted in increased DNaseI expression but no nuclear translocation. This demonstrates that IL-1β promotes nuclear translocation of a cytoplasmic variant of DNaseI since translocation clearly was not dependent on DNase

  17. Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells.

    PubMed

    Tan, Thian Kui; Zheng, Guoping; Hsu, Tzu-Ting; Wang, Ying; Lee, Vincent W S; Tian, Xinrui; Wang, Yiping; Cao, Qi; Wang, Ya; Harris, David C H

    2010-03-01

    As a rich source of pro-fibrogenic growth factors and matrix metalloproteinases (MMPs), macrophages are well-placed to play an important role in renal fibrosis. However, the exact underlying mechanisms and the extent of macrophage involvement are unclear. Tubular cell epithelial-mesenchymal transition (EMT) is an important contributor to renal fibrosis and MMPs to induction of tubular cell EMT. The aim of this study was to investigate the contribution of macrophages and MMPs to induction of tubular cell EMT. The murine C1.1 tubular epithelial cell line and primary tubular epithelial cells were cultured in activated macrophage-conditioned medium (AMCM) derived from lipopolysaccharide-activated J774 macrophages. MMP-9, but not MMP-2 activity was detected in AMCM. AMCM-induced tubular cell EMT in C1.1 cells was inhibited by broad-spectrum MMP inhibitor (GM6001), MMP-2/9 inhibitor, and in AMCM after MMP-9 removal by monoclonal Ab against MMP-9. AMCM-induced EMT in primary tubular epithelial cells was inhibited by MMP-2/9 inhibitor. MMP-9 induced tubular cell EMT in both C1.1 cells and primary tubular epithelial cells. Furthermore, MMP-9 induced tubular cell EMT in C1.1 cells to an extent similar to transforming growth factor-beta. Transforming growth factor-beta-induced tubular cell EMT in C1.1 cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence that MMPs, specifically MMP-9, secreted by effector macrophages can induce tubular cell EMT and thereby contribute to renal fibrosis. PMID:20075196

  18. Method and tool for contracting tubular members by electro-hydraulic forming before hydroforming

    DOEpatents

    Golovashchenko, Sergey Fedorovich

    2011-03-15

    A tubular preform is contracted in an electro-hydraulic forming operation. The tubular preform is wrapped with one or more coils of wire and placed in a chamber of an electro-hydraulic forming tool. The electro-hydraulic forming tool is discharged to form a compressed area on a portion of the tube. The tube is then placed in a hydroforming tool that expands the tubular preform to form a part.

  19. Acute Bronchitis

    MedlinePlus

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  20. The dental management of troublesome twos: renal tubular acidosis and rampant caries

    PubMed Central

    B, Sandhyarani; Huddar, Dayanand; Patil, Anil; Sankeshwari, Banashree

    2013-01-01

    Renal tubular acidosis is a group of disorders in which there is metabolic acidosis due to defect in renal tubular acidification mechanism to maintain normal plasma bicarbonate and blood pH. Irrespective of organ system involved, oral cavity often reflects the disease occurring anywhere in the body. Thus congenital chronic renal diseases, causing acid–base disturbances affects development and structure of the teeth. Chronic renal tubular acidosis causes enamel defects, dental caries, oral candidiasis, angular cheilitis, etc. We hereby present an unusual case report of a 4-year-old boy suffering from renal tubular acidosis associated with rampant caries, whose full mouth rehabilitation has been done. PMID:23667245

  1. High temperature helical tubular receiver for concentrating solar power system

    NASA Astrophysics Data System (ADS)

    Hossain, Nazmul

    In the field of conventional cleaner power generation technology, concentrating solar power systems have introduced remarkable opportunity. In a solar power tower, solar energy concentrated by the heliostats at a single point produces very high temperature. Falling solid particles or heat transfer fluid passing through that high temperature region absorbs heat to generate electricity. Increasing the residence time will result in more heat gain and increase efficiency. A novel design of solar receiver for both fluid and solid particle is approached in this paper which can increase residence time resulting in higher temperature gain in one cycle compared to conventional receivers. The helical tubular solar receiver placed at the focused sunlight region meets the higher outlet temperature and efficiency. A vertical tubular receiver is modeled and analyzed for single phase flow with molten salt as heat transfer fluid and alloy625 as heat transfer material. The result is compared to a journal paper of similar numerical and experimental setup for validating our modeling. New types of helical tubular solar receivers are modeled and analyzed with heat transfer fluid turbulent flow in single phase, and granular particle and air plug flow in multiphase to observe the temperature rise in one cyclic operation. The Discrete Ordinate radiation model is used for numerical analysis with simulation software Ansys Fluent 15.0. The Eulerian granular multiphase model is used for multiphase flow. Applying the same modeling parameters and boundary conditions, the results of vertical and helical receivers are compared. With a helical receiver, higher temperature gain of heat transfer fluid is achieved in one cycle for both single phase and multiphase flow compared to the vertical receiver. Performance is also observed by varying dimension of helical receiver.

  2. Reconstruction of Female Urethra with Tubularized Anterior Vaginal Flap

    PubMed Central

    Sawant, Ajit; Kumar, Vikash; Pawar, Prakash; Tamhankar, Ashwin; Bansal, Sumit; Kapadnis, Lomesh; Savalia, Abhishek

    2016-01-01

    Introduction Female urethral injury is a rare disease. Causes of urethral injuries are prolonged obstructed labour, gynaecological surgeries like vaginoplasty and post traumatic urethral injuries. The present study was conducted to evaluate outcome of female urethral reconstruction using tubularized anterior vaginal wall flap covered with fibroadipose martius flap and autologous fascia sling in patients with urethral loss. Aim Aim of study was to evaluate outcome of reconstruction of female urethra with tubularized anterior vaginal flap. Materials and Methods Retrospective analysis of all the patients with complete urethral loss was done from August 2008 to July 2015. Total seven patients were included in study. All patients presenting with total urethral loss were included. These patients were treated with tubularized anterior vaginal flap. Neourethra was covered with Martius labial flap and autologous fascia lata or rectus abdominis fascia sling. Most common cause of urethral loss was obstructed labour (57.1%). Postoperatively patients were assessed for continence, urine flow rate, ultrasound for upper urinary tract and post void residue. Results Mean operative time was 180 minutes (160-200 minutes) and Intraoperative blood loss was 220ml (170-260 ml). Mean postoperative hospital stay was eight days (seven to nine days) Mean post surgery maximum urine flow rate was more than 15ml/sec (6.7-18.2ml/sec) and mean post void residual urine was 22.5ml (10-50ml). Median follow-up time was 35 months. All patients were catheter free and continent post three weeks of surgery except one patient who developed mild stress urinary incontinence. One patient developed urethral stenosis which was managed by intermittent serial urethral dilatation. Conclusion Female neourethral reconstruction with tabularized anterior vaginal flap and autologous pubovaginal sling is feasible in patients of total urethral loss with success rate of approximately 86%. It should be considered in

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

    PubMed

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

    2015-02-01

    We aimed to record all new patients who presented to departments of oral surgery, oral medicine, and oral and maxillofacial surgery, and to dental hospitals in the UK, with avascular necrosis of the jaws including bisphosphonate-related necrosis (BRONJ) over a 2-year period (1 June 2009-31 May 2011). They were eligible irrespective of age, cause, or coexisting conditions. Data on incidence, clinical characteristics, risk factors, and coexisting conditions were collected. A total of 383 cases were registered: 369 were described as BRONJ, 5 as avascular necrosis, and 9 were unknown. Bisphosphonates had been given orally in 207 (56%), intravenously in 125 (34%), both orally and intravenously in 27 (7%), and was unknown in 9 (2%); one had been given denosumab. The main risk factor was dental extraction, and the mandible was commonly affected. The median duration of administration until onset of BRONJ was 3 years in those treated intravenously and 4 years in those treated orally. Levels of engagement with the study varied between regions, and extrapolation from the 2 most involved (Merseyside and Northern Ireland) found around 8.2-12.8 cases/million/year, which is 508-793 patients/year across the UK. To our knowledge this is one of the first studies to estimate national rates of BRONJ. It confirms that the risk and incidence are low. With changes in trends for antiresorptive bone medication, and increasing numbers of elderly people, it would be useful to repeat the registration in the future. PMID:25497376

  4. Tubular Unimolecular Transmembrane Channels: Construction Strategy and Transport Activities.

    PubMed

    Si, Wen; Xin, Pengyang; Li, Zhan-Ting; Hou, Jun-Li

    2015-06-16

    Lipid bilayer membranes separate living cells from their environment. Membrane proteins are responsible for the processing of ion and molecular inputs and exports, sensing stimuli and signals across the bilayers, which may operate in a channel or carrier mechanism. Inspired by these wide-ranging functions of membrane proteins, chemists have made great efforts in constructing synthetic mimics in order to understand the transport mechanisms, create materials for separation, and develop therapeutic agents. Since the report of an alkylated cyclodextrin for transporting Cu(2+) and Co(2+) by Tabushi and co-workers in 1982, chemists have constructed a variety of artificial transmembrane channels by making use of either the multimolecular self-assembly or unimolecular strategy. In the context of the design of unimolecular channels, important advances have been made, including, among others, the tethering of natural gramicidin A or alamethicin and the modification of various macrocycles such as crown ethers, cyclodextrins, calixarenes, and cucurbiturils. Many of these unimolecular channels exhibit high transport ability for metal ions, particularly K(+) and Na(+). Concerning the development of artificial channels based on macrocyclic frameworks, one straightforward and efficient approach is to introduce discrete chains to reinforce their capability to insert into bilayers. Currently, this approach has found the widest applications in the systems of crown ethers and calixarenes. We envisioned that for macrocycle-based unimolecular channels, control of the arrangement of the appended chains in the upward and/or downward direction would favor the insertion of the molecular systems into bilayers, while the introduction of additional interactions among the chains would further stabilize a tubular conformation. Both factors should be helpful for the formation of new efficient channels. In this Account, we discuss our efforts in designing new unimolecular artificial channels from

  5. Distal renal tubular acidosis and amelogenesis imperfecta: A rare association.

    PubMed

    Ravi, P; Ekambaranath, T S; Arasi, S Ellil; Fernando, E

    2013-11-01

    Renal tubular acidosis (RTA) is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I) is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI) represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previously asymptomatic presented with the hypokalemic paralysis and on work-up found out to have type I RTA. The discoloration of teeth and enamel was diagnosed as AI. PMID:24339526

  6. Type 4 renal tubular acidosis in a kidney transplant recipient.

    PubMed

    Kulkarni, Manjunath

    2016-02-01

    We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment. PMID:27105603

  7. Excitation of symmetric surface wavesby electron tubular beams

    NASA Astrophysics Data System (ADS)

    Akimov, Yu A.; Olefir, V. P.; Azarenkov, N. A.

    2006-08-01

    The nonlinear theory of symmetric surface wave excitation by a low-density electron tubular beam in a cylindrical plasma-vacuum-metal waveguide is presented. A set of nonlinear equations is derived that describes the time evolution of the plasma-beam interaction. The influence of the beam and waveguide structure parameters on the saturation amplitude and excitation efficiency of the surface wave is investigated both numerically and analytically. Thermalization of the electron beam in the wave-fields is studied as well.

  8. [Acute pancreatitis with hypertriglyceridemia--an underestimated disease?].

    PubMed

    Wild, Wolfgang; Tajjiou, Morad; Ferschke, Melanie; Bormann, Fabian; Dörr, Pius; Schwarzbach, Matthias

    2016-01-01

    Hypertriglyceridemia is a rare, but since a long time well known etiology for acute pancreatitis. It could occure alone or coactive with other triggers like alcohlic excess. Nevertheless it found no approach to the current classifications and parameters of prognosis of the acute pancreatitis. We refer about two patients with hypertriglyceridemia and acute pancreatitis, whose initial disease was limited on the tail of the pancreas with just a circumscripted or--in the other case--no necrosis. However, in both cases and although a consequent treatment started immediately, a serious process developed including a life-threatening acute respiratory distress syndrome in one case, which necessitated an extracorporal membrane oxygenation. PMID:26710203

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Percutaneous Access: Acute Effects on Renal Function and Structure in a Porcine Model

    NASA Astrophysics Data System (ADS)

    Handa, Rajash K.; Willis, Lynn R.; Evan, Andrew P.; Connors, Bret A.; Ying, Jun; Fat-Anthony, William; Wind, Kelli R.; Johnson, Cynthia D.; Blomgren, Philip M.; Estrada, Mark C.; Paterson, Ryan F.; Kuo, Ramsay L.; Kim, Samuel C.; Matlaga, Brian R.; Miller, Nicole L.; Watkins, Stephanie L.; Handa, Shelly E.; Lingeman, James E.

    2007-04-01

    Percutaneous nephrolithotomy (PCNL) involves gaining access into the urinary collecting system to remove kidney stones. Animal studies demonstrated that a reduction in renal filtration and perfusion in both kidneys, and a decline in tubular organic anion transport in the treated kidney characterizes the acute (hours) functional response to unilateral percutaneous access. The acute morphologic and histological changes in the treated kidney were consistent with blunt trauma and ischemia. Only tubular organic anion transport remained depressed during the late (3-day) response to the access procedure. Human studies revealed an acute decline in glomerular function and bilateral renal vasoconstriction following unilateral PCNL. Therefore, percutaneous access is not a benign procedure, but is associated with acute functional and structural derangements.

  12. Acute Hematogenous Osteomyelitis in Children.

    PubMed

    Whyte, Noelle S B; Bielski, Robert J

    2016-06-01

    This article discusses the most common organisms associated with acute hematogenous osteomyelitis in children. Magnetic resonance imaging is extremely important in evaluating the extent of the disease process. Osteomyelitis due to methicillin-resistant Staphylococcus aureus can be extremely difficult to treat and eradicate. It spreads quickly and causes local tissue necrosis. It is also associated with other serious sequelae such as deep venous thrombosis and septic pulmonary emboli. A multidisciplinary approach is needed to treat these infections. Hospital stays are often lengthy, complications are frequent, and patients are often critically ill. [Pediatr Ann. 2016;45(6):e204-e208.]. PMID:27294494

  13. Acute interstitial nephritis - a reappraisal and update.

    PubMed

    Raghavan, Rajeev; Eknoyan, Garabed

    2014-09-01

    Acute interstitial nephritis (AIN) is an under recognized and under diagnosed cause of acute kidney injury (AKI). It is estimated to account for 15 - 20% of cases of AKI; it is the reported diagnosis in 2.8% of all kidney biopsies, and 13.5% of biopsies done specifically for acute renal failure. Considerable evidence implicates antigen initiated cell-mediated injury in the pathogenesis of AIN. Drugs account for 70% of all cases, with over 150 different agents incriminated. The remaining cases are due to infections, autoimmune diseases, and rarely idiopathic. The central component of renal injury in AIN is altered tubular function, which usually precedes decrements in filtration rate. The key to early diagnosis is vigilance for the presence of tubular dysfunction in non-oliguric individuals, especially in patients with modest but gradual increments in creatinine level. The utility of urinary biomarkers to diagnose AIN in its early nascent and potentially reversible stage remains to be determined. Prompt recognition, elimination of the offending source of antigen, and use of a limited course of steroid therapy where indicated, will result in complete resolution in ~ 65% of cases, partial resolution in up to 20%, and irreversible damage in the rest. PMID:25079860

  14. Plasma intestinal alkaline phosphatase isoenzymes in neonates with bowel necrosis.

    PubMed Central

    McLachlan, R; Coakley, J; Murton, L; Campbell, N

    1993-01-01

    AIM--To determine if the intestinal isoenzymes of alkaline phosphatase (ALP) are biochemical markers of bowel necrosis in neonates. METHODS--Plasma ALP isoenzymes were measured in 22 babies with bowel necrosis, histologically confirmed, and in 22 matched controls. The isoenzymes were also measured in 16 infants with signs of necrotising enterocolitis, who recovered without histological confirmation of bowel necrosis. The isoenzymes were separated by polyacrylamide gel electrophoresis. Auxiliary tests for identification included neuraminidase digestion and treatment with monoclonal and polyclonal antiplacental antibodies. RESULTS--Intestinal ALP was detected in 16 infants with bowel necrosis--13 had fetal intestinal ALP (FI-ALP) and three had adult intestinal ALP (AI-ALP). FI-ALP was detected in nine of the controls. In the babies with bowel necrosis intestinal ALP was found over all gestations, but in the controls only in those less than 34 weeks. The percentages of total ALP activity due to intestinal ALP were significantly higher in those with bowel necrosis compared with matched controls (p = 0.028). In babies of all gestations diagnostic sensitivity for the presence of intestinal ALP as a marker of bowel necrosis was 73% and diagnostic specificity 59%. In babies greater than 34 weeks' gestation, diagnostic sensitivity fell to 60% but the test became completely specific. In two babies FI-ALP increased from zero/trace to high activity coincident with the episode of bowel necrosis. In 16 babies with signs of necrotising enterocolitis but unconfirmed bowel necrosis FI-ALP was detected in four. CONCLUSION--Intestinal ALP seems to be released into the circulation in some babies with bowel necrosis, but its detection does not have the diagnostic sensitivity and specificity to be a reliable biochemical marker of the condition. Images PMID:8157755

  15. Antioxidant effect of Phyllanthus emblica extract prevents contrast-induced acute kidney injury

    PubMed Central

    2014-01-01

    Background Contrast-induced acute kidney injury (CI-AKI) occurs after the administration of intravenous iodinated contrast agents. Oxidative stress has been proposed as one of the most important mechanisms in the pathogenesis of CI-AKI. The objective of this study was to investigate the antioxidant effect of the extract from Phyllanthus emblica (PE) in preventing CI-AKI. Methods Male Sprague Dawley rats were subjected into eight groups, were given water (control) or PE extract (125 or 250 or 500 mg/kg/day) for 5 days before the induction of CI-AKI. Renal function and oxidative stress markers; malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activity were determined in plasma and renal tissue. Kidney sections were performed for histopathological examination. Results In the contrast media (CM) group, increases in blood urea nitrogen and serum creatinine were demonstrated which correlated with severity of tubular necrosis, peritubular capillary congestion and interstitial edema. Moreover, an increase in MDA and a decrease in TAC SOD and CAT activity in CM group were significantly changed when compared with the control (P < 0.05). In contrast, CI-AKI-induced rats administrated with PE extract 250 and 500 mg/kg/day significantly preserved renal function and attenuated the severity of pathological damage (P < 0.05) as well as significantly lower MDA and higher TAC, SOD and CAT than the CM group (P < 0.05). Conclusions This study demonstrated the protective role of PE extract against CI-AKI. PMID:24755233

  16. Effect of saline loading on uranium-induced acute renal failure in rats

    SciTech Connect

    Hishida, A.; Yonemura, K.; Ohishi, K.; Yamada, M.; Honda, N.

    1988-05-01

    Studies were performed to examine the effect of saline loading on uranium-induced acute renal failure (ARF) in rats. Forty-eight hours after the i.v. injection of uranyl acetate (UA, 5 mg/kg), inulin clearance rate (Cin) decreased to approximately 43% of the control value in water drinking rats (P less than 0.005). Animals receiving continuous isotonic saline infusion following UA showed higher urine flow and Cin (60% of control, P less than 0.01), and lessened intratubular cast formation when compared with water-drinking ARF rats. A short-term saline infusion following UA did not attenuate the decline in Cin (43% of control). An inverse relationship was found between Cin and the number of casts (r = -0.75, P less than 0.01). Multiple regression analysis showed that standardized partial regression coefficient is statistically significant between Cin and cast formation (-0.69, P less than 0.05), but not between Cin and tubular necrosis (-0.07, P greater than 0.05). Renin depletion caused by DOCA plus saline drinking did not attenuate the decline in Cin in ARF (47% of control). No significant difference was found in urinary uranium excretion between water-drinking and saline-infused ARF rats. The findings suggest that continuous saline infusion following UA attenuates the decline in Cin in ARF rats; and that this beneficial effect of saline loading is associated with lessened cast formation rather than with suppressed renin-angiotensin activity or enhanced urinary-uranium excretion.

  17. Preventive effect of pentoxifylline on contrast-induced acute kidney injury in hypercholesterolemic rats

    PubMed Central

    YANG, SHI-KUN; DUAN, SHAO-BIN; PAN, PENG; XU, XIANG-QING; LIU, NA; XU, JUN

    2015-01-01

    Oxidative stress is an important mechanism of contrast-induced acute kidney injury (CIAKI). The optimal strategy to prevent CIAKI remains unclear. The aim of the present study was to assess the effect of pentoxifylline, a nonspecific phosphodiesterase inhibitor, on the prevention of CIAKI. A total of 32 healthy male Sprague-Dawley rats were randomly divided into normal dietary group (NN; n=8) and a high cholesterol-supplemented dietary group (HN; 4% cholesterol and 1% cholic acid; n=24). At the end of eight weeks, the rats in the high cholesterol diet group were randomly divided into three subgroups (n=8 in each group). CIAKI was induced in two of the subgroups via intravenous injection of the radiocontrast media iohexol (10 ml/kg). Pentoxifylline (50 mg/kg) was administered to one of the iohexol-treated groups via intraperitoneal injection 12 h prior to and following contrast media (CM) injection. Kidney function parameters and oxidative stress markers were then measured. The renal pathological changes were evaluated using hematoxylin and eosin staining and scored semi-quantitatively. In iohexol-injected rats, serum creatinine (Scr), renal pathological scores, renal malondialdehyde (MDA) content, renal NADPH oxidase activity, fractional excretion of sodium (FENa%) and fractional excretion of potassium (FEK%) were significantly increased (P<0.01). The Scr, histologic scores, renal MDA content, NADPH oxidase activity, FENa% and FEK% in the rats treated with pentoxifylline prior to iohexol were observed to be reduced compared with those in rats treated with iohexol alone (P<0.01). This suggests that pentoxifylline significantly attenuates renal injuries, including tubular necrosis and proteinaceous casts induced by CM. It may be concluded that pentoxifylline protected the renal tissue from the nephrotoxicity induced by low-osmolar CM via an antioxidant effect. PMID:25574202

  18. Nano-tubular cellulose for bioprocess technology development.

    PubMed

    Koutinas, Athanasios A; Sypsas, Vasilios; Kandylis, Panagiotis; Michelis, Andreas; Bekatorou, Argyro; Kourkoutas, Yiannis; Kordulis, Christos; Lycourghiotis, Alexis; Banat, Ibrahim M; Nigam, Poonam; Marchant, Roger; Giannouli, Myrsini; Yianoulis, Panagiotis

    2012-01-01

    Delignified cellulosic material has shown a significant promotional effect on the alcoholic fermentation as yeast immobilization support. However, its potential for further biotechnological development is unexploited. This study reports the characterization of this tubular/porous cellulosic material, which was done by SEM, porosimetry and X-ray powder diffractometry. The results showed that the structure of nano-tubular cellulose (NC) justifies its suitability for use in "cold pasteurization" processes and its promoting activity in bioprocessing (fermentation). The last was explained by a glucose pump theory. Also, it was demonstrated that crystallization of viscous invert sugar solutions during freeze drying could not be otherwise achieved unless NC was present. This effect as well as the feasibility of extremely low temperature fermentation are due to reduction of the activation energy, and have facilitated the development of technologies such as wine fermentations at home scale (in a domestic refrigerator). Moreover, NC may lead to new perspectives in research such as the development of new composites, templates for cylindrical nano-particles, etc. PMID:22496794

  19. Recent progress in tubular solid oxide fuel cell technology

    SciTech Connect

    Singhal, S.C.

    1997-12-31

    The tubular design of solid oxide fuel cells (SOFCs) and the materials used therein have been validated by successful, continuous electrical testing over 69,000 h of early technology cells built on a calcia-stabilized zirconia porous support tube (PST). In the latest technology cells, the PST has been eliminated and replaced by a doped lanthanum manganite air electrode tube. These air electrode supported (AES) cells have shown a power density increase of about 33% with a significantly improved performance stability over the previously used PST type cells. These cells have also demonstrated the ability to thermally cycle over 100 times without any mechanical damage or performance loss. In addition, recent changes in processes used to fabricate these cells have resulted in significant cost reduction. This paper reviews the fabrication and performance of the state-of-the-art AES tubular cells. It also describes the materials and processing studies that are underway to further reduce the cell cost, and summarizes the recently built power generation systems that employed state-of-the-art AES cells.

  20. Advances in tubular solid oxide fuel cell technology

    SciTech Connect

    Singhal, S.C.

    1996-12-31

    The design, materials and fabrication processes for the earlier technology Westinghouse tubular geometry cell have been described in detail previously. In that design, the active cell components were deposited in the form of thin layers on a ceramic porous support tube (PST). The tubular design of these cells and the materials used therein have been validated by successful electrical testing for over 65,000 h (>7 years). In these early technology PST cells, the support tube, although sufficiently porous, presented an inherent impedance to air flow toward air electrode. In order to reduce such impedance to air flow, the wall thickness of the PST was first decreased from the original 2 mm (the thick-wall PST) to 1.2 mm (the thin-wall PST). The calcia-stabilized zirconia support tube has now been completely eliminated and replaced by a doped lanthanum manganite tube in state-of-the-art SOFCs. This doped lanthanum manganite tube is extruded and sintered to about 30 to 35 percent porosity, and serves as the air electrode onto which the other cell components are fabricated in thin layer form. These latest technology cells are designated as air electrode supported (AES) cells.

  1. Thermal conductivity modeling of core-shell and tubular nanowires.

    PubMed

    Yang, Ronggui; Chen, Gang; Dresselhaus, Mildred S

    2005-06-01

    The heteroepitaxial growth of crystalline core-shell nanostructures of a variety of materials has become possible in recent years, allowing the realization of various novel nanoscale electronic and optoelectronic devices. The increased surface or interface area will decrease the thermal conductivity of such nanostructures and impose challenges for the thermal management of such devices. In the meantime, the decreased thermal conductivity might benefit the thermoelectric conversion efficiency. In this paper, we present modeling results on the lattice thermal conductivity of core-shell and tubular nanowires along the wire axis direction using the phonon Boltzmann equation. We report the dependence of the thermal conductivity on the surface conditions and the core-shell geometry for silicon core-germanium shell and tubular silicon nanowires at room temperature. The results show that the effective thermal conductivity changes not only with the composition of the constituents but also with the radius of the nanowires and nanopores due to the nature of the ballistic phonon transport. The results in this work have implications for the design and operation of a variety of nanoelectronic devices, optoelectronic devices, and thermoelectric materials and devices. PMID:15943452

  2. Toward automated cochlear implant insertion using tubular manipulators

    NASA Astrophysics Data System (ADS)

    Granna, Josephine; Rau, Thomas S.; Nguyen, Thien-Dang; Lenarz, Thomas; Majdani, Omid; Burgner-Kahrs, Jessica

    2016-03-01

    During manual cochlear implant electrode insertion the surgeon is at risk to damage the intracochlear fine-structure, as the electrode array is inserted through a small opening in the cochlea blindly with little force-feedback. This paper addresses a novel concept for cochlear electrode insertion using tubular manipulators to reduce risks of causing trauma during insertion and to automate the insertion process. We propose a tubular manipulator incorporated into the electrode array composed of an inner wire within a tube, both elastic and helically shaped. It is our vision to use this manipulator to actuate the initially straight electrode array during insertion into the cochlea by actuation of the wire and tube, i.e. translation and slight axial rotation. In this paper, we evaluate the geometry of the human cochlea in 22 patient datasets in order to derive design requirements for the manipulator. We propose an optimization algorithm to automatically determine the tube set parameters (curvature, torsion, diameter, length) for an ideal final position within the cochlea. To prove our concept, we demonstrate that insertion can be realized in a follow-the-leader fashion for 19 out of 22 cochleas. This is possible with only 4 different tube/wire sets.

  3. Parallel, fluorous open-tubular chromatography using microstructured fibers.

    PubMed

    Daley, Adam B; Wright, Ramin D; Oleschuk, Richard D

    2011-04-01

    Although commonly used in gas chromatography, open-tubular columns for liquid chromatography have seen their development hindered by a number of factors both theoretical and practical. Requiring small diameters, great lengths and specialized detection systems to achieve a proper chromatographic response, columns of this sort have largely been ignored despite the highly desirable column performance an optimized system would provide. Here, we introduce the use of microstructured fibers (MSFs) as a platform for the development of multiplexed open-tubular liquid chromatography (OTLC) columns. The multiple, parallel silica channels presented by the MSF act as a promising substrate for an OTLC column, as they have diameters near the ideal range for interactions (1-3 μm), minimize flow-induced backpressure through their many uniform paths, and increase the loading capacity compared to a single capillary channel of similar size. Additionally, with outer diameters comparable to regular fused silica capillaries, MSFs can easily be employed in conventional chromatographic systems, eliminating the need for specialized equipment. Finally, MSF columns of this type can be functionalized using silane coupling techniques to allow the introduction of a wide variety of stationary phase chemistries. While in this report we explore the potential and limitations of fluorine-functionalized MSFs as OTLC columns, other stationary phase materials could easily be substituted by choosing appropriate silanization reagents. Particular attention here will be paid to the physical and performance characteristics of the fabricated columns, as well as avenues for their improvement and implementation. PMID:21435484

  4. Understanding shape and morphology of unusual tubular starch nanocrystals.

    PubMed

    Gong, Bei; Liu, Wenxia; Tan, Hua; Yu, Dehai; Song, Zhaoping; Lucia, Lucian A

    2016-10-20

    Starch nanocrystals (SNC) are aptly described as the insoluble degradation byproducts of starch granules that purportedly display morphologies that are platelet-like, round, square, and oval-like. In this work, we reported the preparation of SNC with unprecedented tubular structures through sulfuric acid hydrolysis of normal maize starch, subsequent exposure to ammonia and relaxation at 4°C. High-resolution transmission electron microscopy observation clearly proved that the SNCs possess tubular nanostructures with polygonal cross-section. After further reviewing the transformations of SNC by acid hydrolysis, ammonia treatment, and curing time at 4°C, a mechanism for T-SNC formation is suggested. It is conjectured that T-SNC gradually self-assembles by combination of smaller platelet-like/square nanocrystals likely loosely aggregated by starch molecular chains from residual amorphous regions. This work paves the way for the pursuit of new approaches for the preparation of starch-based nanomaterials possessing unique morphologies. PMID:27474612

  5. Nano-Tubular Cellulose for Bioprocess Technology Development

    PubMed Central

    Koutinas, Athanasios A.; Sypsas, Vasilios; Kandylis, Panagiotis; Michelis, Andreas; Bekatorou, Argyro; Kourkoutas, Yiannis; Kordulis, Christos; Lycourghiotis, Alexis; Banat, Ibrahim M.; Nigam, Poonam; Marchant, Roger; Giannouli, Myrsini; Yianoulis, Panagiotis

    2012-01-01

    Delignified cellulosic material has shown a significant promotional effect on the alcoholic fermentation as yeast immobilization support. However, its potential for further biotechnological development is unexploited. This study reports the characterization of this tubular/porous cellulosic material, which was done by SEM, porosimetry and X-ray powder diffractometry. The results showed that the structure of nano-tubular cellulose (NC) justifies its suitability for use in “cold pasteurization” processes and its promoting activity in bioprocessing (fermentation). The last was explained by a glucose pump theory. Also, it was demonstrated that crystallization of viscous invert sugar solutions during freeze drying could not be otherwise achieved unless NC was present. This effect as well as the feasibility of extremely low temperature fermentation are due to reduction of the activation energy, and have facilitated the development of technologies such as wine fermentations at home scale (in a domestic refrigerator). Moreover, NC may lead to new perspectives in research such as the development of new composites, templates for cylindrical nano-particles, etc. PMID:22496794

  6. Tubular bamboo charcoal for anode in microbial fuel cells

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Li, Jun; Ye, Dingding; Zhu, Xun; Liao, Qiang; Zhang, Biao

    2014-12-01

    The anode material plays a significant role in determining the performance of microbial fuel cells (MFCs). In this study, the bamboo charcoal tube is proposed as a novel anode substrate by carbonizing the natural bamboo. Its surface functional groups, biocompatibility and internal resistance are thoroughly investigated. Performance of the MFCs with a conventional graphite tube anode and a bamboo charcoal tube anode is also compared. The results indicate that the tubular bamboo charcoal anode exhibits advantages over the graphite tube anode in terms of rougher surface, superior biocompatibility and smaller total internal resistance. Moreover, the X-ray photoelectron spectroscopy (XPS) analysis for the bamboo charcoal reveals that the introduced C-N bonds facilitate the electron transfer between the biofilm and electrodes. As a result, the MFC with a bamboo charcoal tube anode achieves a 50% improvement in the maximum power density over the graphite tube case. Furthermore, scale-up of the bamboo charcoal tube anode is demonstrated by employing a bundle of tubular bamboo charcoal to reach higher power output.

  7. Tubular dielectric elastomer actuator for active fluidic control

    NASA Astrophysics Data System (ADS)

    McCoul, David; Pei, Qibing

    2015-10-01

    We report a novel low-profile, biomimetic dielectric elastomer tubular actuator capable of actively controlling hydraulic flow. The tubular actuator has been established as a reliable tunable valve, pinching a secondary silicone tube completely shut in the absence of a fluidic pressure bias or voltage, offering a high degree of resistance against fluidic flow, and able to open and completely remove this resistance to flow with an applied low power actuation voltage. The system demonstrates a rise in pressure of ∼3.0 kPa when the dielectric elastomer valve is in the passive, unactuated state, and there is a quadratic fall in this pressure with increasing actuation voltage, until ∼0 kPa is reached at 2.4 kV. The device is reliable for at least 2000 actuation cycles for voltages at or below 2.2 kV. Furthermore, modeling of the actuator and fluidic system yields results consistent with the observed experimental dependence of intrasystem pressure on input flow rate, actuator prestretch, and actuation voltage. To our knowledge, this is the first actuator of its type that can control fluid flow by directly actuating the walls of a tube. Potential applications may include an implantable artificial sphincter, part of a peristaltic pump, or a computerized valve for fluidic or pneumatic control.

  8. Vibration dampener for dampening vibration of a tubular member

    DOEpatents

    Obermeyer, Franklin D.; Middlebrooks, Willis B.; DeMario, Edmund E.

    1994-01-01

    Vibration dampener for dampening vibration of a tubular member, such as an instrumentation tube of the type found in nuclear reactor pressure vessels. The instrumentation tube is received in an outer tubular member, such as a guide thimble tube. The vibration dampener comprises an annular sleeve which is attachable to the inside surface of the guide thimble tube and which is sized to surround the instrumentation tube. Dimples are attached to the interior wall of the sleeve for radially supporting the instrumentation tube. The wall of the sleeve has a flexible spring member, which is formed from the wall, disposed opposite the dimples for biasing the instrumentation tube into abutment with the dimples. Flow-induced vibration of the instrumentation tube will cause it to move out of contact with the dimples and further engage the spring member, which will flex a predetermined amount and exert a reactive force against the instrumentation tube to restrain its movement. The amount by which the spring member will flex is less than the unrestrained amplitude of vibration of the instrumentation tube. The reactive force exerted against the instrumentation tube will be sufficient to return it to its original axial position within the thimble tube. In this manner, vibration of the instrumentation tube is dampened so that in-core physics measurements are accurate and so that the instrumentation tube will not wear against the inside surface of the guide thimble tube.

  9. Vibration dampener for dampening vibration of a tubular member

    DOEpatents

    Obermeyer, F.D.; Middlebrooks, W.B.; DeMario, E.E.

    1994-10-18

    Vibration dampener for dampening vibration of a tubular member, such as an instrumentation tube of the type found in nuclear reactor pressure vessels is disclosed. The instrumentation tube is received in an outer tubular member, such as a guide thimble tube. The vibration dampener comprises an annular sleeve which is attachable to the inside surface of the guide thimble tube and which is sized to surround the instrumentation tube. Dimples are attached to the interior wall of the sleeve for radially supporting the instrumentation tube. The wall of the sleeve has a flexible spring member, which is formed from the wall, disposed opposite the dimples for biasing the instrumentation tube into abutment with the dimples. Flow-induced vibration of the instrumentation tube will cause it to move out of contact with the dimples and further engage the spring member, which will flex a predetermined amount and exert a reactive force against the instrumentation tube to restrain its movement. The amount by which the spring member will flex is less than the unrestrained amplitude of vibration of the instrumentation tube. The reactive force exerted against the instrumentation tube will be sufficient to return it to its original axial position within the thimble tube. In this manner, vibration of the instrumentation tube is dampened so that in-core physics measurements are accurate and so that the instrumentation tube will not wear against the inside surface of the guide thimble tube. 14 figs.

  10. Glutamatergic Signaling Maintains the Epithelial Phenotype of Proximal Tubular Cells

    PubMed Central

    Bozic, Milica; de Rooij, Johan; Parisi, Eva; Ortega, Marta Ruiz; Fernandez, Elvira

    2011-01-01

    Epithelial–mesenchymal transition (EMT) contributes to the progression of renal tubulointerstitial fibrosis. The N-methyl-d-aspartate receptor (NMDAR), which is present in proximal tubular epithelium, is a glutamate receptor that acts as a calcium channel. Activation of NMDAR induces actin rearrangement in cells of the central nervous system, but whether it helps maintain the epithelial phenotype of the proximal tubule is unknown. Here, knockdown of NMDAR1 in a proximal tubule cell line (HK-2) induced changes in cell morphology, reduced E-cadherin expression, and increased α-SMA expression. Induction of EMT with TGF-β1 led to downregulation of both E-cadherin and membrane-associated β-catenin, reorganization of F-actin, expression of mesenchymal markers de novo, upregulation of Snail1, and increased cell migration; co-treatment with NMDA attenuated all of these changes. Furthermore, NMDA reduced TGF-β1–induced phosphorylation of Erk1/2 and Akt and the activation of Ras, suggesting that NMDA antagonizes TGF-β1–induced EMT by inhibiting the Ras-MEK pathway. In the unilateral ureteral obstruction model, treatment with NMDA blunted obstruction-induced upregulation of α-SMA, FSP1, and collagen I and downregulation of E-cadherin. Taken together, these results suggest that NMDAR plays a critical role in preserving the normal epithelial phenotype and modulating tubular EMT. PMID:21597037

  11. Surface and interfacial creases in a bilayer tubular soft tissue

    NASA Astrophysics Data System (ADS)

    Razavi, Mir Jalil; Pidaparti, Ramana; Wang, Xianqiao

    2016-08-01

    Surface and interfacial creases induced by biological growth are common types of instability in soft biological tissues. This study focuses on the criteria for the onset of surface and interfacial creases as well as their morphological evolution in a growing bilayer soft tube within a confined environment. Critical growth ratios for triggering surface and interfacial creases are investigated both analytically and numerically. Analytical interpretations provide preliminary insights into critical stretches and growth ratios for the onset of instability and formation of both surface and interfacial creases. However, the analytical approach cannot predict the evolution pattern of the model after instability; therefore nonlinear finite element simulations are carried out to replicate the poststability morphological patterns of the structure. Analytical and computational simulation results demonstrate that the initial geometry, growth ratio, and shear modulus ratio of the layers are the most influential factors to control surface and interfacial crease formation in this soft tubular bilayer. The competition between the stretch ratios in the free and interfacial surfaces is one of the key driving factors to determine the location of the first crease initiation. These findings may provide some fundamental understanding in the growth modeling of tubular biological tissues such as esophagi and airways as well as offering useful clues into normal and pathological functions of these tissues.

  12. Numerical investigation of cavitation performance on bulb tubular turbine

    NASA Astrophysics Data System (ADS)

    Sun, L. G.; Guo, P. C.; Zheng, X. B.; Luo, X. Q.

    2016-05-01

    The cavitation flow phenomena may occur in the bulb tubular turbine at some certain operation conditions, which even decrease the performance of units and causes insatiably noise and vibration when it goes worse. A steady cavitating flow numerical simulations study is carried out on the bulb tubular unit with the same blade pitch angle and different guide vane openings by using the commercial code ANSYS CFX in this paper. The phenomena of cavitation induction areas and development process are obtained and draws cavitation performance curves. The numerical results show that the travelling bubble cavity is the main types of cavitation development over a wide operating range of discharge and this type of cavitation begins to sensitive to the value of cavitation number when the discharge exceeding a certain valve, in this condition, it can lead to a severe free bubble formation with the gradually decrement of cavitation number. The reported cavitation performance curves results indicate that the flow blockage incident would happen because of a mount of free bubble formation in the flow passage when the cavity developed to certain extend, which caused head drop behavior and power broken dramatically and influenced the output power.

  13. Additive manufacturing of patient-specific tubular continuum manipulators

    NASA Astrophysics Data System (ADS)

    Amanov, Ernar; Nguyen, Thien-Dang; Burgner-Kahrs, Jessica

    2015-03-01

    Tubular continuum robots, which are composed of multiple concentric, precurved, elastic tubes, provide more dexterity than traditional surgical instruments at the same diameter. The tubes can be precurved such that the resulting manipulator fulfills surgical task requirements. Up to now the only material used for the component tubes of those manipulators is NiTi, a super-elastic shape-memory alloy of nickel and titan. NiTi is a cost-intensive material and fabrication processes are complex, requiring (proprietary) technology, e.g. for shape setting. In this paper, we evaluate component tubes made of 3 different thermoplastic materials (PLA, PCL and nylon) using fused filament fabrication technology (3D printing). This enables quick and cost-effective production of custom, patient-specific continuum manipulators, produced on site on demand. Stress-strain and deformation characteristics are evaluated experimentally for 16 fabricated tubes of each thermoplastic with diameters and shapes equivalent to those of NiTi tubes. Tubes made of PCL and nylon exhibit properties comparable to those made of NiTi. We further demonstrate a tubular continuum manipulator composed of 3 nylon tubes in a transnasal, transsphenoidal skull base surgery scenario in vitro.

  14. Helical DNA origami tubular structures with various sizes and arrangements.

    PubMed

    Endo, Masayuki; Yamamoto, Seigi; Emura, Tomoko; Hidaka, Kumi; Morone, Nobuhiro; Heuser, John E; Sugiyama, Hiroshi

    2014-07-14

    We developed a novel method to design various helical tubular structures using the DNA origami method. The size-controlled tubular structures which have 192, 256, and 320 base pairs for one turn of the tube were designed and prepared. We observed the formation of the expected short tubes and unexpected long ones. Detailed analyses of the surface patterns of the tubes showed that the short tubes had mainly a left-handed helical structure. The long tubes mainly formed a right-handed helical structure and extended to the directions of the double helical axes as structural isomers of the short tubes. The folding pathways of the tubes were estimated by analyzing the proportions of short and long tubes obtained at different annealing conditions. Depending on the number of base pairs involved in one turn of the tube, the population of left-/right-handed and short/long tubes changed. The bending stress caused by the stiffness of the bundled double helices and the non-natural helical pitch determine the structural variety of the tubes. PMID:24888699

  15. Leptospirosis: an ignored cause of acute renal failure in Taiwan.

    PubMed

    Yang, C W; Pan, M J; Wu, M S; Chen, Y M; Tsen, Y T; Lin, C L; Wu, C H; Huang, C C

    1997-12-01

    Leptospirosis, caused by a spirochete, is the most common zoonosis in domestic or wild animals. Animals excrete infected urine in soil or water and may cause human infections through abrased wound, mucosa, conjunctiva, or by swallowing contaminated water. Clinical presentations of leptospirosis are mostly subclinical. Five to ten percent of leptospirosis are fatal, causing fever, hemorrhage, jaundice, and acute renal failure (Weil's syndrome). Leptospirosis has been ignored as a cause of acute renal failure in Taiwan. We report two patients with leptospirosis who presented with high fever, abdominal pain, jaundice, and acute renal failure. Patient 1 died on day 12 of admission of multiple organ failure associated with pancytopenia, hypogammaglobulinemia, and reactive hemophagocytosis. Leptospirosis was recognized after death. Patient 2 was admitted with similar presentations 2 weeks later. Penicillin and doxycycline were given early in the course, and azotemia, jaundice, respiratory failure, and aseptic meningitis gradually improved. Renal biopsy showed interstitial nephritis. Several tubular clearance tests showed proximal tubular defect with severe bicarbonate wasting (FeHCO3- 20.9%) and incomplete type II renal tubular acidosis without affecting the distal nephron. After 80 days of treatment, this patient was discharged with recovery of conscious level and renal function. This is the first leptospirosis patient with detailed tubular functional and morphological studies of the kidney. Diagnosis of leptospirosis was made by microscopic agglutination test (MAT) for antibody to leptospira and by polymerase chain reaction (PCR) for leptospira DNA in blood and urine (interrogans serogroup australis in case 1 and Leptospira borgpetersenii serogroup ballum in case 2). Because active surveillance has resulted in 13 cases diagnosed as leptospirosis islandwide thereafter, underestimation and ignorance of leptospirosis as a cause of acute renal failure may occur in Taiwan

  16. Acute hemorrhage within intradural extramedullary schwannoma in cervical spine presenting with quadriparesis

    PubMed Central

    Sahoo, Ranjan Kumar; Das, Pulin Bihari; Sarangi, Gouri Sankar; Mohanty, Sureswar

    2015-01-01

    Schwannoma with acute hemorrhage is rarely seen. A 44-years-old male patient presented with complaint of neck pain and acute onset of quadriparesis. Magnetic resonance imaging (MRI) of his cervical spine revealed evidence of an intradural extramedullary tumor with intratumoral acute hemorrhage. He was operated in emergency and the mass was found to be schwannoma with acute hemorrhage. Post operatively the patient improved significantly. Though schwannomas show microscopic intratumoral hemorrhage and necrosis at times, schwannoma with acute hemorrhage resulting acute onset of neurological deficit is very uncommon. PMID:25972715

  17. Immunization with viral antigens: infectious haematopoietic necrosis.

    PubMed

    Winton, J R

    1997-01-01

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

  18. Pyelo-ureteral necrosis after renal transplantation.

    PubMed

    Spasovski, Goce B; Masin-Spasovska, Jelka; Stavridis, Sotir; Saiti, Skender; Lekovski, Ljupco

    2008-01-01

    Because of the limited chance of receiving a kidney transplant (for several well-known reasons), a lot of desperate dialysis patients procure an unrelated donor kidney transplant against all medical advice. This type of renal paid transplantation is associated with many surgical complications and invasive opportunistic infections that increase the morbidity and mortality in this group of transplant recipients. In this report, we describe a case of a 22-year-old girl with a segmental infarction of the graft lower pole and a complete pyelo-ureteral necrosis as a consequence of some vascular damage, complicated by a pathohistological finding of an invasive candidiasis. Despite the successful surgical pyelovesical anastomosis and the good recovery of the patient and the kidney, long-term prognosis remains poor. The lack of information from the transplanting center regarding both donor and recipient and the associated, unacceptable risks on the graft and patient survival in unrelated, paid transplant recipients reinforce the standpoint that this practice should be abandoned. PMID:18204913

  19. [An infected necrosis of the chin].

    PubMed

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

    2016-07-01

    A 51-year-old man was referred by his dentist to a maxillofacial surgeon with complaints of illness and pain in the mandible, associated with a rapidly expanding area of black gingiva and mucosa surrounding the lower front teeth. Clinically and radiographically there was evidence of an infected necrosis of the chin and floor of mouth. Following debridement at the operating room, the patient was treated at the intensive care unit for septic shock leading to prolonged hospitalisation. Investigation of the bone marrow did not provide an explanation for pancytopenia or the severity of the illness. In addition, genetic investigation of thiopurine S-methyltransferase gene showed no mutations. This gene codes for an identically named protein enzyme that contributes in the metabolising of the medicine azathioprine, used daily for an autoimmune disease. A combination of the use of azathioprine, a folic acid deficiency and sepsis led to this exceptional course of illness. Therapeutic intervention consisted of surgical debridement and treatment of the bacteraemia. Afterwards several corrective surgeries were necessary to restore oral functions. PMID:27430038

  20. Clinical studies with tumour necrosis factor.

    PubMed

    Spriggs, D R; Sherman, M L; Frei, E; Kufe, D W

    1987-01-01

    The mechanism of tumour necrosis factor (TNF) cytotoxicity remains unknown. The in vivo antitumour effects of TNF may be related to direct cytotoxicity, immunomodulatory effects or endothelial effects on tumour vasculature. Phase I and early Phase II clinical trials of human recombinant TNF are under way in Japan, the USA, the UK and Germany. The maximum Phase II dose for TNF has not been established. The clinical toxicity of TNF is generally similar to that of other biological agents. Systemic toxicity, including fever, chills, anorexia and nausea, has been seen in most patients treated with TNF and has not been clearly related to dose. Other toxicities have included liver function abnormalities, hypotension, transient neurological changes and haematological abnormalities. Few clinical responses have been reported but organized Phase II testing remains to be completed. Combination trials with interferons have recently been initiated. Phase II efficacy studies of TNF as a single agent and in combination are needed for an assessment of the value of this agent in cancer therapy. PMID:3330011

  1. Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity

    PubMed Central

    Nishihara, Kumiko; Masuda, Satohiro; Shinke, Haruka; Ozawa, Aiko; Ichimura, Takaharu; Yonezawa, Atsushi; Nakagawa, Shunsaku; Inui, Ken-ichi; Bonventre, Joseph V.; Matsubara, Kazuo

    2014-01-01

    Because of the difficulty in detecting segment-specific response in the kidney, we investigated the molecular events underlying acute kidney injury in the proximal tubules of rats with cisplatin (cis-diamminedichloroplatinum II)-induced nephrotoxicity. Microarray analysis revealed that mRNA levels of several cytokines and chemokines, such as interleukin-1beta, chemokine (C-C motif) ligand (CCL) 2, CCL20, chemokine (C-X-C motif) ligand (CXCL) 1, and CXCL10 were significantly increased after cisplatin treatment in both isolated proximal tubules and whole kidney. Interestingly, tubular CCL2 mRNA levels increased soon after cisplatin administration, whereas CCL2 mRNA levels in whole kidney first decreased and then increased. Levels of both CCL2 and kidney injury molecule-1 (KIM-1) in the whole kidney increased after cisplatin administration. Immunofluorescence analysis revealed CCL2 changes in the proximal tubular cells initially and then in the medullary interstitium. Urinary CCL2 excretion significantly increased approximately 3-fold compared with controls the day after cisplatin administration (5 mg/kg), when no changes were observed plasma creatinine and blood urea nitrogen levels. Urinary levels of KIM-1 also increased 3-fold after cisplatin administration. In addition, urinary CCL2 rather than KIM-1 increased in chronic renal failure rats after administration of low-dose cisplatin (2 mg/kg), suggesting that urinary CCL2 was selective for cisplatin-induced nephrotoxicity in renal impairment. These results indicated that the increase in cytokine and chemokine expression in renal epithelial cells might be responsible for kidney deterioration in cisplatin-induced nephrotoxicity, and that urinary CCL2 is associated with tubular injury and serves as a sensitive and noninvasive marker for the early detection of cisplatin-induced tubular injury. PMID:23291264

  2. Epigenetics in acute kidney injury

    PubMed Central

    Tang, Jinhua; Zhuang, Shougang

    2015-01-01

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

  3. Acute copper toxicosis in the Canada goose.

    PubMed

    Henderson, B M; Winterfield, R W

    1975-01-01

    Acute copper toxicosis resulted in Canada geese, Branta canadensis, following ingestion of copper sulfate at about 600mg/kg from a small man-made pond on a game farm. The lesions were those associated with copper toxicosis in other avian species. The primary pathologic change was necrosis and sloughing of the proventriculus and gizzard. A greenish discoloration of the lungs also occurred. PMID:1156262

  4. Acute dental pain, Part II: Diagnosis and emergency treatment.

    PubMed

    Antonelli, J R

    1990-09-01

    Part II of this two-part series differentiates and explores endodontic-related emergencies with reversible and irreversible pulpitis. Indications and contra-indications for vital pulp therapy are explained, and treatment is outlined. The inflammatory process involved in irreversible pulpal disease is summarized, and the clinical signs, symptoms, and treatment of irreversible pulpitis (with and without acute periradicular involvement, with pulp necrosis, and acute periradicular abscess with and without cellulitis) are discussed. PMID:2097056

  5. Carbon monoxide poisoning and nonoliguric acute renal failure.

    PubMed Central

    Bessoudo, R.; Gray, J.

    1978-01-01

    Carbon monoxide poisoning in a 37-year-old man was complicated by neurologic damage, skin changes, muscle necrosis and nonoliguric renal failure. The relation between nontraumatic rhabdomyolysis and acute renal failure in carbon monoxide poisoning is reviewed. Recognition of the acute renal failure in such cases is important, for this complication can be fatal; the prognosis is excellent, however, if proper medical management is provided. PMID:679099

  6. Primary gradient defect distal renal tubular acidosis presenting as hypokalaemic periodic paralysis.

    PubMed

    Koul, P A; Wahid, A; Bhat, F A

    2005-07-01

    A 45 year old man presented with recurrent hypokalaemic paralysis. Laboratory investigations revealed renal tubular acidosis as the cause of the hypokalaemia, and dynamic tubular studies suggested a gradient defect as the underlying cause. The patient had associated dextrocardia. To our knowledge, this is the first report of this condition. PMID:15983101

  7. Expanded plug method for developing circumferential mechanical properties of tubular materials

    DOEpatents

    Hendrich, William Ray; McAfee, Wallace Jefferson; Luttrell, Claire Roberta

    2006-11-28

    A method for determining the circumferential properties of a tubular product, especially nuclear fuel cladding, utilizes compression of a polymeric plug within the tubular product to determine strain stress, yield stress and other properties. The process is especially useful in the determination of aging properties such as fuel rod embrittlement after long burn-down.

  8. Optimization of production conditions and material characteristics of tubular stabilizer bars

    NASA Astrophysics Data System (ADS)

    Muhr, R.

    1983-08-01

    Weight reduction of car tubular stabilizer bars is studied. Optimization of prematerial, forming and tempering procedures, and surface treatment are discussed. Steel qualities and production conditions were examined for feasibility with sample stabilizer bars. It is concluded that tubular stabilizer bars can be manufactured and practically used in cars. Tube diameters must not be too small, otherwise the weight saving is minimal.

  9. Tubular lysosome morphology and distribution within macrophages depend on the integrity of cytoplasmic microtubules

    SciTech Connect

    Swanson, J.; Bushnell, A.; Silverstein, S.C.

    1987-04-01

    Pinocytosis of the fluorescent dye lucifer yellow labels elongated, membrane-bound tubular organelles in several cell types, including cultured human monocytes, thioglycolate-elicited mouse peritoneal macrophages, and the macrophage-like cell line J774.2. These tubular structures can be identified as lysosomes by acid phosphatase histochemistry and immunofluorescence localization of cathepsin L. The abundance of tubular lysosomes is markedly increased by treatment with phorbol 12-myristate 13-acetate. When labeled by pinocytosis of microperoxidase and examined by electron microscopic histochemistry, the tubular lysosomes have an outside diameter of approx. = 75 nm and a length of several micrometers; they radiate from the cell's centrosphere in alignment with cytoplasmic microtubules and intermediate filaments. Incubation of phorbol myristate acetate-treated macrophages at 4/sup 0/C or in medium containing 5 ..mu..M colchicine or nocodazole at 37/sup 0/C leads to disassembly of microtubules and fragmentation of the tubular lysosomes. Return of the cultures to 37/sup 0/C or removal of nocodazole from the medium leads to reassembly of microtubules and the reappearance of tubular lysosomes within 10-20 min. The authors conclude that microtubules are essential for the maintenance of tubular lysosome morphology and that, in macrophages, a significant proportion of the lysosomal compartment is contained within these tubular structures.

  10. Low gas prices and rig count cut business for makers of oil country tubular goods

    SciTech Connect

    1995-09-01

    After years of scavenging used drill pipe and trying everything they could think of to make existing pipe last, contractors in the petroleum industry are buying more new pipe. Although supplies of tubular goods are growing tighter, the supply and demand curves haven`t met. However, while the market for drill pipe may be increasing, the market for other tubular goods is decreasing.

  11. 78 FR 77420 - Certain Oil Country Tubular Goods From the Republic of Turkey: Preliminary Negative...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-23

    ... Duty Investigations, 78 FR 45505 (July 29, 2013). \\2\\ Maverick Tube Corporation, United States Steel... International Trade Administration Certain Oil Country Tubular Goods From the Republic of Turkey: Preliminary... tubular goods (OCTG) from the Republic of Turkey (Turkey). The period of investigation is January 1,...

  12. Responses of Proximal Tubular Cells to Injury in Congenital Renal Disease: Fight or Flight

    PubMed Central

    Chevalier, Robert L.; Forbes, Michael S.; Galarreta, Carolina I.; Thornhill, Barbara A.

    2013-01-01

    Most chronic kidney disease in children results from congenital or inherited disorders, which can be studied in mouse models. Following 2 weeks of unilateral ureteral obstruction (UUO) in the adult mouse, nephron loss is due to proximal tubular mitochondrial injury and cell death. In neonatal mice, proximal tubular cell death is delayed beyond 2 weeks of complete UUO, and release of partial UUO allows remodeling of remaining nephrons. Progressive cyst expansion develops in polycystic kidney disease (PKD), a common inherited renal disorder. The PCY mutant mouse (which develops late-onset PKD) develops thinning of the glomerulotubular junction in parallel with growth of cysts in adulthood. Renal insufficiency in nephropathic cystinosis, a rare inherited renal disorder, results from progressive tubular cystine accumulation. In the Ctns knock out mouse (a model of cystinosis), proximal tubular cells become flattened, with loss of mitochondria and thickening of tubular basement membrane. In each model, persistent obstructive or metabolic stress leads ultimately to the formation of atubular glomeruli. The initial “fight” response (proximal tubular survival) switches to a “flight” response (proximal tubular cell death) with ongoing oxidative injury and mitochondrial damage. Therapies should be directed at reducing proximal tubular mitochondrial oxidative injury to enhance repair and regeneration. PMID:23949631

  13. Proximal tubular renal dysfunction or damage in HIV-infected patients.

    PubMed

    Del Palacio, María; Romero, Sara; Casado, José L

    2012-01-01

    Antiretroviral-associated toxicity, especially in the case of tenofovir plus boosted protease inhibitors, could affect different functions of the proximal renal tubule. Considering the long-term use of antiretroviral therapy and the concomitant presence of other risk factors, several degrees of proximal tubular toxicity, from chronic subclinical renal dysfunction to Fanconi syndrome, could be observed in HIV-infected patients. However, the clinical significance of isolated tubular dysfunction, in the short and long term, remains unclear. In addition, primary tubular abnormalities, even severe, may be missed until they affect the glomerular function. Therefore, there is a need for new biomarkers, not only based in serum creatinine and estimated glomerular filtration rates, that might help to identify tubular cell toxicity and predict the clinical outcome in HIV-infected patients. Increased values of urinary beta-2-microglobulin and retinol-binding protein, observed in up to 70% of patients, have been associated to tenofovir-associated mitochondrial dysfunction. Together with other tubular parameters or in isolation, both biomarkers could be useful for diagnosing proximal tubular toxicity. Other molecules, such as urinary kidney injury molecule- 1, neutrophil gelatinase associated lipocalin, or N-acetyl-b-D-glucosaminidase, could help to distinguish between tubular cell damage and dysfunction. Here, we review the current knowledge on tubular toxicity in HIV-infected patients on antiretroviral therapy. PMID:22833061

  14. 78 FR 52213 - Certain Oil Country Tubular Goods From India, Korea, the Philippines, Saudi Arabia, Taiwan...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-22

    ... Commission, Washington, DC, and by publishing the notice in the Federal Register of July 10, 2013 (78 FR... COMMISSION Certain Oil Country Tubular Goods From India, Korea, the Philippines, Saudi Arabia, Taiwan..., and Vietnam of certain oil country tubular goods, provided for primarily in subheadings 7304.29,...

  15. Electrospinning of small diameter 3-D nanofibrous tubular scaffolds with controllable nanofiber orientations for vascular grafts.

    PubMed

    Wu, Huijun; Fan, Jintu; Chu, Chih-Chang; Wu, Jun

    2010-12-01

    The control of nanofiber orientation in nanofibrous tubular scaffolds can benefit the cell responses along specific directions. For small diameter tubular scaffolds, however, it becomes difficult to engineer nanofiber orientation. This paper reports a novel electrospinning technique for the fabrication of 3-D nanofibrous tubular scaffolds with controllable nanofiber orientations. Synthetic absorbable poly-ε-caprolactone (PCL) was used as the model biomaterial to demonstrate this new electrospinning technique. Electrospun 3-D PCL nanofibrous tubular scaffolds of 4.5 mm in diameter with different nanofiber orientations (viz. circumferential, axial, and combinations of circumferential and axial directions) were successfully fabricated. The degree of nanofiber alignment in the electrospun 3-D tubular scaffolds was quantified by using the fast Fourier transform (FFT) analysis. The results indicated that excellent circumferential nanofiber alignment could be achieved in the 3-D nanofibrous PCL tubular scaffolds. The nanofibrous tubular scaffolds with oriented nanofibers had not only directional mechanical property but also could facilitate the orientation of the endothelial cell attachment on the fibers. Multiple layers of aligned nanofibers in different orientations can produce 3-D nanofibrous tubular scaffolds of different macroscopic properties. PMID:20890639

  16. Acute kidney injury.

    PubMed

    Patschan, Daniel; Müller, Gerhard Anton

    2015-01-01

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

  17. Acute kidney injury

    PubMed Central

    Müller, Gerhard Anton

    2015-01-01

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

  18. Histone lysine crotonylation during acute kidney injury in mice

    PubMed Central

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

    2016-01-01

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

  19. Early growth response 1 regulates glucose deprivation-induced necrosis

    PubMed Central

    JEON, HYUN MIN; LEE, SU YEON; JU, MIN KYUNG; KIM, CHO HEE; PARK, HYE GYEONG; KANG, HO SUNG

    2013-01-01

    Necrosis is commonly found in the core region of solid tumours due to metabolic stress such as hypoxia and glucose deprivation (GD) resulting from insufficient vascularization. Necrosis promotes tumour growth and development by releasing the tumour-promoting cytokine high mobility group box 1 (HMGB1); however, the molecular mechanism underlying necrotic cell death remains largely unknown. In this study, we show that early growth response 1 (Egr-1) is induced in a reactive oxygen species (ROS)-dependent manner by GD in several cell lines such as A549, MDA-MB-231 and HepG2 cells that exhibit necrosis upon GD. We found that Egr-1 short hairpin RNA (shRNA) prevented GD-induced necrosis and HMGB1 release. Necrosis-inhibiting activity of Egr-1 shRNA was also seen in multicellular tumour spheroids (MTSs), an in vitro tumour model system. In contrast, Egr-1 overexpression appeared to make tumour cells more susceptible to GD-induced necrosis. Finally, Egr-1 shRNA suppressed the growth of MTSs. These findings demonstrate that Egr-1 is implicated in GD-induced necrosis and tumour progression. PMID:23152075

  20. Andrographolide-induced apoptosis in human renal tubular epithelial cells: Roles of endoplasmic reticulum stress and inflammatory response.

    PubMed

    Gu, Li-Li; Zhang, Xin-Yue; Xing, Wen-Min; Xu, Jia-Dong; Lu, Hong

    2016-07-01

    Andrographolide sodium bisulfate as a kind of soluble derivative of andrographolide (AD), is obviously known to be nephrotoxicity, but AD has not been reported clearly. Our study aimed to investigate the induction of apoptosis in human renal tubular epithelial (HK-2) cells by AD and its possible mechanism. Our results demonstrated that AD (0-250μmol/L) inhibited Hk-2 cells proliferation in a dose- and time-dependent manner and induced apoptosis, accompanied by decreased of superoxide dismutase (SOD) activity and increased of malondialdehvde (MDA) content. Simultaneously, AD regulated the expression of endoplasmic reticulum (ER) molecular chaperone glucose-regulated protein 78 (GRP78/Bip) protein, elevated the expressions of C/EBP homologous protein (CHOP) and Caspase-4, indicating activation of ER stress signaling, and induced the alterative expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) proteins. It provided evidence that ER stress and inflammation would be significant mechanisms responsible for AD-induced apoptosis in addition to oxidative stress. PMID:27344125