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Sample records for acute tubular damage

  1. Acute tubular necrosis

    MedlinePlus

    ... Liver disease and kidney damage caused by diabetes ( diabetic nephropathy ) may make a person more susceptible to the ... Urine sodium Urine specific gravity and osmolarity urine Treatment In most people, ATN is reversible. The goal ...

  2. Renal ischaemia, transient glomerular leak and acute renal tubular damage in patients envenomed by Russell's vipers (Daboia russelii siamensis) in Myanmar.

    PubMed

    Tin-Nu-Swe; Tin-Tun; Myint-Lwin; Thein-Than; Tun-Pe; Robertson, J I; Leckie, B J; Phillips, R E; Warrell, D A

    1993-01-01

    Fifty-two patients who had been bitten by Russell's vipers in Myanmar developed acute renal failure (serum creatinine exceeding 1.3 mg/dL). Thirty-four of them (65%) became oliguric, but the other 18 (35%) maintained a urine output of more than 400 mL/24 h. In oliguric patients, gastrointestinal haemorrhages, renal angle tenderness and conjunctival oedema occurred more commonly, and peak serum creatinine, blood urea nitrogen and the fractional excretion of sodium were significantly higher (P < 0.01) than in non-oliguric patients, indicating a greater degree of renal damage. Urinary concentrations of beta 2 microglobulin and retinol binding protein were raised in most of the patients indicating failure of proximal tubular reabsorption of these proteins, while high urinary N-acetyl glucosaminidase concentrations were consistent with renal tubular damage. Plasma concentrations of active renin were very high, suggesting that renal ischaemia, associated with activation of the renin-angiotensin system, was involved in the development of renal dysfunction.

  3. Tubular kidney damage and centrilobular liver injury after intratracheal instillation of dimethyl selenide.

    PubMed

    Cherdwongcharoensuk, Duangrudee; Henrique, Rui; Upatham, Suchart; Pereira, António Sousa; Aguas, Artur P

    2005-01-01

    Accidental inhalation of selenium (Se) derivatives, such as dimethyl selenide (DMSe), has been associated with damage of respiratory tissues. However, systemic effects of inhaled Se have not been thoroughly established. We have investigated whether mouse kidney and liver show cellular pathology as a result of a single intratracheal instillation of two different doses of DMSe (0.05 and 0.1 mg Se/kg BW). The animals were sacrificed 1, 7, 14, and 28 days after either 1 of the 2 DMSe treatments; samples were studied by light microscopy. Instillation of the low DMSe dose resulted in acute and transient tubular disease of the kidney expressed by swelling and vacuolation of epithelial cells of proximal tubules; in some mice, tubular necrosis was observed. After 14 days of the DMSe treatment, these lesions were ameliorated and, by day 28, the kidney tubular epithelium depicted a normal morphology. The same low dose of DMSe caused sustained damage to centrilobular hepatocytes characterized by swollen and vacuolized liver cells. After the instillation of the high DMSe dose, the mice presented sustained liver and kidney focal necrosis. Our data suggest that inhalation of DMSe results in: (i) acute tubular injury of the kidney and damage to centrilobular liver cells and (ii) this systemic pathology induced by DMSe is a dose-dependent phenomenon.

  4. Tubular cell apoptosis and cidofovir-induced acute renal failure.

    PubMed

    Ortiz, Alberto; Justo, Pilar; Sanz, Ana; Melero, Rosa; Caramelo, Carlos; Guerrero, Manuel Fernández; Strutz, Frank; Müller, Gerhard; Barat, Antonio; Egido, Jesus

    2005-01-01

    Cidofovir is an antiviral drug with activity against a wide array of DNA viruses including poxvirus. The therapeutic use of cidofovir is marred by a dose-limiting side effect, nephrotoxicity, leading to proximal tubular cell injury and acute renal failure. Treatment with cidofovir requires the routine use of prophylactic measures. A correct knowledge of the cellular and molecular mechanisms of cidofovir toxicity may lead to the development of alternative prophylactic strategies. We recently cared for a patient with irreversible acute renal failure due to cidofovir. Renal biopsy showed tubular cell apoptosis. Cidofovir induced apoptosis in primary cultures of human proximal tubular cells in a temporal (peak apoptosis at 7 days) and concentration (10-40 microg/ml) pattern consistent with that of clinical toxicity. Apoptosis was identified by the presence of hypodiploid cells, by the exposure of annexin V binding sites and by morphological features and was associated with the appearance of active caspase-3 fragments. Cell death was specific as it was also present in a human proximal tubular epithelial cell line (HK-2), but not in a human kidney fibroblast cell line, and was prevented by probenecid. An inhibitor of caspase-3 (DEVD) prevented cidofovir apoptosis. The survival factors present in serum, insulin-like growth factor-1 and hepatocyte growth factor, were also protective. The present data suggest that apoptosis induction is a mechanism contributing to cidofovir nephrotoxicity. The prophylactic administration of factors with survival activity for tubular epithelium should be further explored in cidofovir renal injury.

  5. 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.

  6. Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease.

    PubMed

    Wu, Chia-Lin; Su, Tzu-Cheng; Chang, Chia-Chu; Kor, Chew-Teng; Chang, Chung-Ho; Yang, Tao-Hsiang; Chiu, Ping-Fang; Tarng, Der-Cherng

    2017-02-27

    Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13-71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.

  7. Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease

    PubMed Central

    Wu, Chia-Lin; Su, Tzu-Cheng; Chang, Chia-Chu; Kor, Chew-Teng; Chang, Chung-Ho; Yang, Tao-Hsiang; Chiu, Ping-Fang; Tarng, Der-Cherng

    2017-01-01

    Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13–71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD. PMID:28240739

  8. Early onset acute tubular necrosis following single infusion of zoledronate

    PubMed Central

    Yachoui, Ralph

    2016-01-01

    Summary Zoledronate is a highly potent bisphosphonate widely used in the treatment of postmenopausal osteoporosis. We report the first occurrence of toxic acute tubular necrosis (ATN) following treatment with zoledronate in a patient with osteoporosis. A 63-year-old Caucasian female with rheumatoid arthritis on anti-immune agents received a single dose of zoledronic acid (reclast) for worsening osteoporosis. Twelve days later, she developed renal failure with a rise in serum creatinine from a baseline level of 1.1 mg/dL to 5.5 mg/dL. Renal biopsy showed toxic ATN. Zoledronate was discontinued and the patient had subsequent gradual improvement in renal function with final serum creatinine of 1.8 mg/dL at 1 month of follow up. Careful monitoring of serum creatinine and awareness of the potential nephrotoxicity may avert the development of acute renal failure in osteoporosis patients treated with this agent. PMID:27920815

  9. NADPH oxidase 4 deficiency increases tubular cell death during acute ischemic reperfusion injury

    PubMed Central

    Nlandu-Khodo, Stellor; Dissard, Romain; Hasler, Udo; Schäfer, Matthias; Pircher, Haymo; Jansen-Durr, Pidder; Krause, Karl Heinz; Martin, Pierre-Yves; de Seigneux, Sophie

    2016-01-01

    NADPH oxidase 4 (NOX4) is highly expressed in kidney proximal tubular cells. NOX4 constitutively produces hydrogen peroxide, which may regulate important pro-survival pathways. Renal ischemia reperfusion injury (IRI) is a classical model mimicking human ischemic acute tubular necrosis. We hypothesized that NOX4 plays a protective role in kidney IRI. In wild type (WT) animals subjected to IRI, NOX4 protein expression increased after 24 hours. NOX4 KO (knock-out) and WT littermates mice were subjected to IRI. NOX4 KO mice displayed decreased renal function and more severe tubular apoptosis, decreased Bcl-2 expression and higher histologic damage scores compared to WT. Activation of NRF2 was decreased in NOX4 KO mice in response to IRI. This was related to decreased KEAP1 oxidation leading to decreased NRF2 stabilization. This resulted in decreased glutathione levels. In vitro silencing of NOX4 in cells showed an enhanced propensity to apoptosis, with reduced expression of NRF2, glutathione content and Bcl-2 expression, similar to cells derived from NOX4 KO mice. Overexpression of a constitutively active form of NRF2 (caNRF2) in NOX4 depleted cells rescued most of this phenotype in cultured cells, implying that NRF2 regulation by ROS issued from NOX4 may play an important role in its anti-apoptotic property. PMID:27924932

  10. Changes in free and esterified cholesterol: hallmarks of acute renal tubular injury and acquired cytoresistance.

    PubMed

    Zager, R A; Kalhorn, T F

    2000-09-01

    Acute tubular cell injury is accompanied by plasma membrane phospholipid breakdown. Although cholesterol is a dominant membrane lipid which interdigitates with, and impacts, phospholipid homeostasis, its fate during the induction and recovery phases of acute renal failure (ARF) has remained ill defined. The present study was performed to ascertain whether altered cholesterol expression is a hallmark of evolving tubular damage. Using gas chromatographic analysis, free cholesterol (FC) and esterified cholesterol (CE) were quantified in: 1) isolated mouse proximal tubule segments (PTS) after 30 minutes of hypoxic or oxidant (ferrous ammonium sulfate) injury; 2) cultured proximal tubule (HK-2) cells after 4 or 18 hours of either ATP depletion/Ca(2+) ionophore- or ferrous ammonium sulfate-mediated injury; and 3) in renal cortex 18 hours after induction of glycerol-induced myoglobinuric ARF, a time corresponding to the so-called "acquired cytoresistance" state (ie, resistance to further renal damage). Hypoxic and oxidant injury each induced approximately 33% decrements in CE (but not FC) levels in PTS, corresponding with lethal cell injury ( approximately 50 to 60% LDH release). When comparable CE declines were induced in normal PTS by exogenous cholesterol esterase treatment, proportionate lethal cell injury resulted. During models of slowly evolving HK-2 cell injury, progressive CE increments occurred: these were first noted at 4 hours, and reached approximately 600% by 18 hours. In vivo myoglobinuric ARF produced comparable renal cortical CE (and to a lesser extent FC) increments. Renal CE accumulation strikingly correlated with the severity of ARF (eg, blood urea nitrogen versus CE; r, 0.84). Mevastatin blocked cholesterol accumulation in injured HK-2 cells, indicating de novo synthesis was responsible. Acute tubule injury first lowers, then raises, tubule cholesterol content. Based on previous observations that cholesterol has cytoprotectant properties, the present

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

    PubMed

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

    2014-07-01

    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.

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

    PubMed

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

    2016-04-07

    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.

  13. 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

  14. MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury

    PubMed Central

    Thomasova, Dana; Ebrahim, Martrez; Fleckinger, Kristina; Li, Moying; Molnar, Jakob; Popper, Bastian; Liapis, Helen; Kotb, Ahmed M; Siegerist, Florian; Endlich, Nicole; Anders, Hans-Joachim

    2016-01-01

    Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and we hypothesized that MDM2 is necessary for their survival and homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise of tubular cells in vitro. This phenotype was completely rescued by concomitant knockdown of p53, thus suggesting p53 dependency. In vivo experiments in the zebrafish model demonstrated that the tubulus cells of the larvae undergo cell death after the knockdown of mdm2. Doxycycline-induced deletion of MDM2 in tubular cell-specific MDM2-knockout mice Pax8rtTa-cre; MDM2f/f caused acute kidney injury with increased plasma creatinine and blood urea nitrogen and sharp decline of glomerular filtration rate. Histological analysis showed massive swelling of renal tubular cells and later their loss and extensive tubular dilation, markedly in proximal tubules. Ultrastructural changes of tubular epithelial cells included swelling of the cytoplasm and mitochondria with the loss of cristae and their transformation in the vacuoles. The pathological phenotype of the tubular cell-specific MDM2-knockout mouse model was completely rescued by co-deletion of p53. Tubular epithelium compensates only partially for the cell loss caused by MDM2 depletion by proliferation of surviving tubular cells, with incomplete MDM2 deletion, but rather mesenchymal healing occurs. We conclude that MDM2 is a non-redundant survival factor for proximal tubular cells by protecting them from spontaneous p53 overexpression-related cell death. PMID:27882940

  15. TRIP13-deficient tubular epithelial cells are susceptible to apoptosis following acute kidney injury

    PubMed Central

    Pressly, Jeffrey D.; Hama, Taketsugu; Brien, Shannon O’; Regner, Kevin R.; Park, Frank

    2017-01-01

    Damage to renal tubular epithelial cells by genetic, environmental, or biological insults can initiate complex signaling mechanisms that promote kidney repair and functional recovery. In this study, we demonstrated that thyroid receptor interacting protein 13 (TRIP13) is a critical modulator of tubular epithelial cell repair following ischemia‐reperfusion injury (IRI), a common type of renal stressor. In Trip13Gt/Gthypomorph mice treated with unilateral renal IRI, persistent tubular epithelial cell damage was determined in the IRI-treated kidney throughout the 168 hours of experimental period compared to the contralateral kidneys. The damaged epithelial cells were associated with increased levels of DNA damage (ɣH2AX) and apoptotic markers (p53, cleaved caspase-7, and TUNEL-positive cells). Correspondingly, TRIP13 was found to directly interact with Tetratricopeptide Repeat Domain 5 (TTC5), a p53 co‐factor, and genetic knockdown of TRIP13 in murine inner medullary collecting duct cells in the presence of hydrogen peroxide showed increased activity of p53 at Serine 15. In all, these studies suggest that insufficient TRIP13 increased the susceptibility of damaged tubular epithelial cells to progress towards apoptotic cell death. PMID:28256593

  16. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    SciTech Connect

    Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S.; Coppes, Rob P.; Stewart, Fiona A.

    2014-07-01

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.

  17. Endoplasmic reticulum stress and its effects on renal tubular cells apoptosis in ischemic acute kidney injury.

    PubMed

    Xu, Yan; Guo, Min; Jiang, Wei; Dong, Hui; Han, Yafei; An, Xiao-Fei; Zhang, Jisheng

    2016-06-01

    Ischemia is the most frequent cause of acute kidney injury (AKI), which is characterized by apoptosis of renal tubular cell. A common result of ischemia in AKI is dysfunction of endoplasmic reticulum (ER), which causes the protein-folding capacity to lag behind the protein-folding load. The abundance of misfolded proteins stressed the ER and results in induction of the unfolded protein response (UPR). While the UPR is an adaptive response, over time it can result in apoptosis when cells are unable to recover quickly. Recent research suggests that ER stress is a major factor in renal tubular cell apoptosis resulting from ischemic AKI. Thus, ER stress may be an important new progression factor in the pathology of ischemic AKI. In this article, we review UPR signaling, describe pathology and pathophysiology mechanisms of ischemic AKI, and highlight the dual function of ER stress on renal tubular cell apoptosis.

  18. Acute abdomen secondary to complete tubular colonic duplication

    PubMed Central

    Castejón-Casado, Javier; Muñoz Miguelsanz, MA; Diaz, E. Moreno; Gomez, M. Garcia; Garcia, MA Padilla; Valade, R. Fernandez

    2014-01-01

    We report the case of a 6-month-old infant who presented with a complete duplication of the large intestine, debuting clinically with acute abdomen and severe metabolic disorders. We discuss the pathogenesis and morphology of the lesions, diagnostic difficulties and peculiarities of surgical treatment. PMID:25197196

  19. Tubular cross talk in acute kidney injury: a story of sense and sensibility.

    PubMed

    El-Achkar, Tarek M; Dagher, Pierre C

    2015-06-15

    The mammalian kidney is an organ composed of numerous functional units or nephrons. Beyond the filtering glomerulus of each nephron, various tubular segments with distinct populations of epithelial cells sequentially span the kidney from cortex to medulla. The highly organized folding of the tubules results in a spatial distribution that allows intimate contact between various tubular subsegments. This unique arrangement can promote a newly recognized type of horizontal epithelial-to-epithelial cross talk. In this review, we discuss the importance of this tubular cross talk in shaping the response of the kidney to acute injury in a sense and sensibility model. We propose that injury-resistant tubules such as S1 proximal segments and thick ascending limbs (TAL) can act as "sensors" and thus modulate the responsiveness or "sensibility" of the S2-S3 proximal segments to injury. We also discuss new findings that highlight the importance of tubular cross talk in regulating homeostasis and inflammation not only in the kidney, but also systemically.

  20. GDF11 improves tubular regeneration after acute kidney injury in elderly mice

    PubMed Central

    Zhang, Ying; Li, Qinggang; Liu, Dong; Huang, Qi; Cai, Guangyan; Cui, Shaoyuan; Sun, Xuefeng; Chen, Xiangmei

    2016-01-01

    The GDF11 expression pattern and its effect on organ regeneration after acute injury in the elderly population are highly controversial topics. In our study, GDF11/8 expression increased after kidney ischemia–reperfusion injury (IRI), and the relatively lower level of GDF11/8 in the kidneys of aged mice was associated with a loss of proliferative capacity and a decline in renal repair, compared to young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2′-deoxyuridine (EdU)-positive proximal tubular epithelial cells. GDF11 improved the renal repair, recovery of renal function, and survival of elderly mice at 72 h after IRI. Moreover, the addition of recombinant GDF11 to primary renal epithelial cells increased proliferation, migration, and dedifferentiation by upregulating the ERK1/2 pathway in vitro. Our study indicates that GDF11/8 in the kidney decreases with age and that GDF11 can increase tubular cell dedifferentiation and proliferation as well as improve tubular regeneration after acute kidney injury (AKI) in old mice. PMID:27703192

  1. Tubular overexpression of Gremlin in transgenic mice aggravates renal damage in diabetic nephropathy.

    PubMed

    Marchant, Vanessa; Droguett, Alejandra; Valderrama, Graciela; Burgos, M Eugenia; Carpio, Daniel; Kerr, Bredford; Ruiz-Ortega, Marta; Egido, Jesús; Mezzano, Sergio

    2015-09-15

    Diabetic nephropathy (DN) is currently a leading cause of end-stage renal failure worldwide. Gremlin was identified as a gene differentially expressed in mesangial cells exposed to high glucose and in experimental diabetic kidneys. We have described that Gremlin is highly expressed in biopsies from patients with diabetic nephropathy, predominantly in areas of tubulointerstitial fibrosis. In streptozotocin (STZ)-induced experimental diabetes, Gremlin deletion using Grem1 heterozygous knockout mice or by gene silencing, ameliorates renal damage. To study the in vivo role of Gremlin in renal damage, we developed a diabetic model induced by STZ in transgenic (TG) mice expressing human Gremlin in proximal tubular epithelial cells. The albuminuria/creatinuria ratio, determined at week 20 after treatment, was significantly increased in diabetic mice but with no significant differences between transgenic (TG/STZ) and wild-type mice (WT/STZ). To assess the level of renal damage, kidney tissue was analyzed by light microscopy (periodic acid-Schiff and Masson staining), electron microscopy, and quantitative PCR. TG/STZ mice had significantly greater thickening of the glomerular basement membrane, increased mesangial matrix, and podocytopenia vs. WT/STZ. At the tubulointerstitial level, TG/STZ showed increased cell infiltration and mild interstitial fibrosis. In addition, we observed a decreased expression of podocin and overexpression of monocyte chemoattractant protein-1 and fibrotic-related markers, including transforming growth factor-β1, Col1a1, and α-smooth muscle actin. Together, these results show that TG mice overexpressing Gremlin in renal tubules develop greater glomerular and tubulointerstitial injury in response to diabetic-mediated damage and support the involvement of Gremlin in diabetic nephropathy.

  2. Target organ damage in acute heart failure.

    PubMed

    Casado Cerrada, J; Zabaleta Camino, J P; Fontecha Ortega, M

    2016-03-01

    Acute heart failure is a prognostic factor due to its high mortality during the acute phase and the increased frequency of medium to long-term adverse events. The pathophysiological mechanisms triggered during these exacerbations can persist after reaching clinical stability, remaining even after the acute episode has ended. A certain degree of neurohormonal activation, oxidative stress, apoptosis and inflammation (among other conditions) can therefore persist, resulting in organ damage, not just of the myocardium but likely the entire cardiovascular apparatus. This new insight into the persistence of harmful mechanisms that last beyond the exacerbations could be the start of a change in perspective for developing new therapeutic strategies that seek an overall control of hemodynamic and congestive changes that occur during acute decompensated heart failure and changes that remain after achieving clinical stability.

  3. Brain damage complicating septic shock: acute haemorrhagic leucoencephalitis as a complication of the generalised Shwartzman reaction.

    PubMed Central

    Graham, D I; Behan, P O; More, I A

    1979-01-01

    The neuropathological findings in six patients who developed neurological signs after the onset of "septic shock" caused by Gram-negative septicaemia are described. The changes in the brains were characteristic of acute haemorrhagic leucoencephalitis, and there was evidence, particularly in the kidneys, of disseminated intravascular coagulation with tubular necrosis and, in some, appearances indistinguishable from membrano-proliferative glomerulonephritis. It is agreed that acute haemorrhagic leucoencephalitis is another manifestation of a generalised Shwartzman reaction, and it is suggested that activation of complement is the final common pathway that produces tissue damage in the brain and kidney. Images PMID:762582

  4. Markers of tubular dysfunction.

    PubMed

    Piscator, M

    1989-03-01

    Since the first description of tubular proteinuria in 1958, much progress has been made with regard to diagnostic means for detecting small changes in the function of the proximal tubule. Small increases in the excretion of low-molecular-weight proteins can now be determined with great accuracy. Determination of total protein is an economic way of screening large populations but does not give specific information on the type of damage. Determinations of glucose, phosphate and amino acids are relatively insensitive methods, since their excretion is also dependent on diet and nutritional status. Determination of high-molecular-weight enzymes released from damaged tubular cells may be of use for studies of acute as well as chronic effects of nephrotoxic agents, but more data are needed.

  5. Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats.

    PubMed

    Yildirim, Zeki; Sogut, Sadik; Odaci, Ersan; Iraz, Mustafa; Ozyurt, Huseyin; Kotuk, Mahir; Akyol, Omer

    2003-02-01

    The effect of oral erdosteine on tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are investigated in the cisplatin model of acute renal failure in rats. A single dose of cisplatin caused kidney damage manifested by kidney histology as well as increases in plasma creatinine and blood urea nitrogen (BUN) levels. Treatment with free radical scavenger erdosteine attenuated increases in plasma creatinine and BUN, and tissue MDA and NO levels, and provided a histologically-proven protection against cisplatin-induced acute renal failure. Erdosteine also reduced depletion in the tissue CAT, GSH-Px, and SOD activities. These results show that erdosteine may be a promising drug for protection against cisplatin-induced nephrotoxicity. However, further studies with different doses of erdosteine are warranted for clarifying the issue.

  6. Damage analysis of CFRP-confined circular concrete-filled steel tubular columns by acoustic emission techniques

    NASA Astrophysics Data System (ADS)

    Li, Dongsheng; Chen, Zhi; Feng, Quanming; Wang, Yanlei

    2015-08-01

    Damage properties of carbon fiber-reinforced polymer (CFRP) confined circular concrete-filled steel tubular (CCFT) columns were analyzed through acoustic emission (AE) signals. AE characteristic parameters were obtained through axial compression tests. The severity of damage to CFRP-CCFT columns was estimated using the growing trend of AE accumulated energy as basis. The bearing capacity of CFRP-CCFT columns and AE accumulated energy improved as CFRP layers increased. The damage process was studied using a number of crucial AE parameters. The cracks’ mode can be differentiated through the ratio of the rise time to the waveform amplitude and through average frequency analysis. With the use of intensity signal analysis, the damage process of the CFRP-CCFT columns can be classified into three levels that represent different degrees. Based on b-value analysis, the development of the obtained cracks can be defined. Thus, identifying an initial yielding and providing early warning is possible.

  7. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells.

    PubMed

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian; Thomale, Jürgen; Schupp, Nicole; Fritz, Gerhard

    2016-02-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury.

  8. 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

  9. Characterisation of Damaged Tubular Composites by Acoustic Emission, Thermal Diffusivity Mapping and TSR-RGB Projection Technique

    NASA Astrophysics Data System (ADS)

    Chandarana, Neha; Lansiaux, Henri; Gresil, Matthieu

    2016-11-01

    An increase in the use of composite materials, owing to improved design and fabrication processes, has led to cost reductions in many industries. Resistance to corrosion, high specific strength, and stiffness are just a few of their many attractive properties. However, damage tolerance remains a major concern in the implementation of composites and uncertainty regarding component lifetimes can lead to over-design and under-use of such materials. A combination of non-destructive evaluation (NDE) and structural health monitoring (SHM) have shown promise in improving confidence by enabling data collection in-situ and in real time. In this work, infrared thermography (IRT) is employed for NDE of tubular composite specimens before and after impact. Four samples are impacted with energies of 5 J, 7.5 J, and 10 J by an un-instrumented falling weight set-up. Acoustic emissions (AE) are monitored using bonded piezoelectric sensors during one of the four impact tests. IRT data is used to generate diffusivity and thermal depth mappings of each sample using the thermographic signal reconstruction (TSR) red green blue (RGB) projection technique. Analysis of AE data alone for a 10 J impact suggest significant damage to the fibres and matrix; this is in good agreement with the generated thermal depth mappings for each sample, which indicate damage through multiple fibre layers. IRT and AE data are correlated and validated by optical micrographs taken along the cross section of damage.

  10. Characterisation of Damaged Tubular Composites by Acoustic Emission, Thermal Diffusivity Mapping and TSR-RGB Projection Technique

    NASA Astrophysics Data System (ADS)

    Chandarana, Neha; Lansiaux, Henri; Gresil, Matthieu

    2017-04-01

    An increase in the use of composite materials, owing to improved design and fabrication processes, has led to cost reductions in many industries. Resistance to corrosion, high specific strength, and stiffness are just a few of their many attractive properties. However, damage tolerance remains a major concern in the implementation of composites and uncertainty regarding component lifetimes can lead to over-design and under-use of such materials. A combination of non-destructive evaluation (NDE) and structural health monitoring (SHM) have shown promise in improving confidence by enabling data collection in-situ and in real time. In this work, infrared thermography (IRT) is employed for NDE of tubular composite specimens before and after impact. Four samples are impacted with energies of 5 J, 7.5 J, and 10 J by an un-instrumented falling weight set-up. Acoustic emissions (AE) are monitored using bonded piezoelectric sensors during one of the four impact tests. IRT data is used to generate diffusivity and thermal depth mappings of each sample using the thermographic signal reconstruction (TSR) red green blue (RGB) projection technique. Analysis of AE data alone for a 10 J impact suggest significant damage to the fibres and matrix; this is in good agreement with the generated thermal depth mappings for each sample, which indicate damage through multiple fibre layers. IRT and AE data are correlated and validated by optical micrographs taken along the cross section of damage.

  11. Hydroxyethylstarch impairs renal function and induces interstitial proliferation, macrophage infiltration and tubular damage in an isolated renal perfusion model

    PubMed Central

    Hüter, Lars; Simon, Tim-Philipp; Weinmann, Lenard; Schuerholz, Tobias; Reinhart, Konrad; Wolf, Gunter; Amann, Kerstin Ute; Marx, Gernot

    2009-01-01

    Introduction The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours. Methods Infusion of either 10% HES 200/0.5, 6% HES 130/0.42 or Ringer's lactate (RL) was performed to achieve an haematocrit of 20% in eight kidneys from four animals per group. Physiological and pathophysiological parameters were determined (including N-acetyl-beta-aminoglucosidase as a marker for lysosomal tubular damage). Histological investigations and immunohistological stainings of the kidneys were performed. Results Initially after haemodilution, HES 130/0.42 and HES 200/0.5 reduced urine output compared with RL (P < 0.01). After six hours, N-acetyl-beta-aminoglucosidase was significantly higher in HES 200/0.5 (81 ± 23 U/L) compared with HES 130/0.42 (38 ± 12 U/L) and RL (21 ± 13 U/L; P < 0.001). Osmotic nephrosis-like lesions (OL) of the tubuli were present in all groups showing a significantly lower number of OL in RL (1.1 ± 0.4; P = 0.002) compared with both HES groups (HES 200/0.5 = 2.1 ± 0.6; HES 130/0.42 = 2.0 ± 0.5). Macrophage infiltration was significantly higher in HES 200/0.5 compared with HES 130/0.42 (1.3 ± 1.0 vs. 0.2 ± 0.04; P = 0.044). There was a significant increase in interstitial cell proliferation in the HES 200/0.5 group vs. HES 130/0.42 (18.0 ± 6.9 vs. 6.5 ± 1.6; P = 0.006) with no significant difference in RL (13.5 ± 4.0). Conclusions We observed impaired diuresis and sodium excretion by HES and identified renal interstitial proliferation, macrophage infiltration and tubular damage as potential pathological mechanisms of HES-induced adverse effects on renal function using an isolated porcine renal perfusion model. Furthermore, we demonstrated that 10% HES 200/0.5 had more of a pro-inflammatory effect compared with 6% HES 130/0.42 and caused more pronounced tubular damage than 6% HES 130/0.42 and

  12. Renal Cortical Lactate Dehydrogenase: A Useful, Accurate, Quantitative Marker of In Vivo Tubular Injury and Acute Renal Failure

    PubMed Central

    Zager, Richard A.; Johnson, Ali C. M.; Becker, Kirsten

    2013-01-01

    Studies of experimental acute kidney injury (AKI) are critically dependent on having precise methods for assessing the extent of tubular cell death. However, the most widely used techniques either provide indirect assessments (e.g., BUN, creatinine), suffer from the need for semi-quantitative grading (renal histology), or reflect the status of residual viable, not the number of lost, renal tubular cells (e.g., NGAL content). Lactate dehydrogenase (LDH) release is a highly reliable test for assessing degrees of in vitro cell death. However, its utility as an in vivo AKI marker has not been defined. Towards this end, CD-1 mice were subjected to graded renal ischemia (0, 15, 22, 30, 40, or 60 min) or to nephrotoxic (glycerol; maleate) AKI. Sham operated mice, or mice with AKI in the absence of acute tubular necrosis (ureteral obstruction; endotoxemia), served as negative controls. Renal cortical LDH or NGAL levels were assayed 2 or 24 hrs later. Ischemic, glycerol, and maleate-induced AKI were each associated with striking, steep, inverse correlations (r, −0.89) between renal injury severity and renal LDH content. With severe AKI, >65% LDH declines were observed. Corresponding prompt plasma and urinary LDH increases were observed. These observations, coupled with the maintenance of normal cortical LDH mRNA levels, indicated the renal LDH efflux, not decreased LDH synthesis, caused the falling cortical LDH levels. Renal LDH content was well maintained with sham surgery, ureteral obstruction or endotoxemic AKI. In contrast to LDH, renal cortical NGAL levels did not correlate with AKI severity. In sum, the above results indicate that renal cortical LDH assay is a highly accurate quantitative technique for gauging the extent of experimental acute ischemic and toxic renal injury. That it avoids the limitations of more traditional AKI markers implies great potential utility in experimental studies that require precise quantitation of tubule cell death. PMID:23825563

  13. Human CD133+ Renal Progenitor Cells Induce Erythropoietin Production and Limit Fibrosis After Acute Tubular Injury

    PubMed Central

    Aggarwal, Shikhar; Grange, Cristina; Iampietro, Corinne; Camussi, Giovanni; Bussolati, Benedetta

    2016-01-01

    Persistent alterations of the renal tissue due to maladaptive repair characterize the outcome of acute kidney injury (AKI), despite a clinical recovery. Acute damage may also limit the renal production of erythropoietin, with impairment of the hemopoietic response to ischemia and possible lack of its reno-protective action. We aimed to evaluate the effect of a cell therapy using human CD133+ renal progenitor cells on maladaptive repair and fibrosis following AKI in a model of glycerol-induced rhabdomyolysis. In parallel, we evaluated the effect of CD133+ cells on erythropoietin production. Administration of CD133+ cells promoted the restoration of the renal tissue, limiting the presence of markers of injury and pro-inflammatory molecules. In addition, it promoted angiogenesis and protected against fibrosis up to day 60. No effect of dermal fibroblasts was observed. Treatment with CD133+ cells, but not with PBS or fibroblasts, limited anemia and increased erythropoietin levels both in renal tissue and in circulation. Finally, CD133+ cells contributed to the local production of erythropoietin, as observed by detection of circulating human erythropoietin. CD133+ cells appear therefore an effective source for cell repair, able to restore renal functions, including erythropoietin release, and to limit long term maldifferentiation and fibrosis. PMID:27853265

  14. Pharmacogenetics may Influence Tacrolimus Daily Dose, but not Urinary Tubular Damage Markers in the Long-Term Period after Renal Transplantation

    PubMed Central

    Stefanović, Nikola Z.; Cvetković, Tatjana P.; Veličković-Radovanović, Radmila M.; Jevtović-Stoimenov, Tatjana M.; Vlahović, Predrag M.; Stojanović, Ivana R.; Pavlović, Dušica D.

    2015-01-01

    Summary Background The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients. Methods The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-β-D-glucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage. Results The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with TT genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients’ genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes’ activities. Conclusions Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug’s tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress. PMID:28356851

  15. Preconditioning with Triiodothyronine Improves the Clinical Signs and Acute Tubular Necrosis Induced by Ischemia/Reperfusion in Rats

    PubMed Central

    Ferreyra, Carla; Vargas, Félix; Rodríguez-Gómez, Isabel; Pérez-Abud, Rocío; O'Valle, Francisco; Osuna, Antonio

    2013-01-01

    Background Renal ischemia/reperfusion (I/R) injury is manifested by acute renal failure (ARF) and acute tubular necrosis (ATN). The aim of this study was to evaluate the effectiveness of preconditioning with 3, 3, 5 triiodothyronine (T3) to prevent I/R renal injury. Methodology/Principal Findings The rats were divided into four groups: sham-operated, placebo-treated (SO-P), sham-operated T3- treated (SO- T3), I/R-injured placebo-treated (IR-P), and I/R-injured T3-treated (IR- T3) groups. At 24 h before ischemia, the animals received a single dose of T3 (100 μg/kg). Renal function and plasma, urinary, and tissue variables were studied at 4, 24, and 48 h of reperfusion, including biochemical, oxidative stress, and inflammation variables, PARP-1 immunohistochemical expression, and ATN morphology. In comparison to the SO groups, the IR-P groups had higher plasma urea and creatinine levels and greater proteinuria (at all reperfusion times) and also showed: increased oxidative stress-related plasma, urinary, and tissue variables; higher plasma levels of IL6 (proinflammatory cytokine); increased glomerular and tubular nuclear PARP-1 expression; and a greater degree of ATN. The IR-T3 group showed a marked reduction in all of these variables, especially at 48 h of reperfusion. No significant differences were observed between SO-P and SO-T3 groups. Conclusions This study demonstrates that preconditioning rats with a single dose of T3 improves the clinical signs and ATN of renal I/R injury. These beneficial effects are accompanied by reductions in oxidative stress, inflammation, and renal PARP-1 expression, indicating that this sequence of factors plays an important role in the ATN induced by I/R injury. PMID:24086411

  16. Damage evaluation of fiber reinforced plastic-confined circular concrete-filled steel tubular columns under cyclic loading using the acoustic emission technique

    NASA Astrophysics Data System (ADS)

    Li, Dongsheng; Du, Fangzhu; Ou, Jinping

    2017-03-01

    Glass-fiber reinforced plastic (GFRP)-confined circular concrete-filled steel tubular (CCFT) columns comprise of concrete, steel, and GFRP and show complex failure mechanics under cyclic loading. This paper investigated the failure mechanism and damage evolution of GFRP–CCFT columns by performing uniaxial cyclic loading tests that were monitored using the acoustic emission (AE) technique. Characteristic AE parameters were obtained during the damage evolution of GFRP–CCFT columns. Based on the relationship between the loading curve and these parameters, the damage evolution of GFRP–CCFT columns was classified into three stages that represented different damage degrees. Damage evolution and failure mode were investigated by analyzing the b-value and the ratio of rise time to waveform amplitude and average frequency. The damage severity of GFRP–CCFT columns were quantitatively estimated according to the modified index of damage and NDIS-2421 damage assessment criteria corresponding to each loading step. The proposed method can explain the damage evolution and failure mechanism for GFRP–CCFT columns and provide critical warning information for composite structures.

  17. Patients with ischaemic, mixed and nephrotoxic acute tubular necrosis in the intensive care unit – a homogeneous population?

    PubMed Central

    Santos, Wilson JQ; Zanetta, Dirce MT; Pires, Antonio C; Lobo, Suzana MA; Lima, Emerson Q; Burdmann, Emmanuel A

    2006-01-01

    Introduction Acute tubular necrosis (ATN) is usually studied as a single entity, without distinguishing between ischaemic, nephrotoxic and mixed aetiologies. In the present study we evaluated the characteristics and outcomes of patients with ATN by aetiological group. Method We conducted a retrospective comparison of clinical features, mortality rates and risk factors for mortality for the three types of ATN in patients admitted to the general intensive care unit of a university hospital between 1997 and 2000. Results Of 593 patients with acute renal failure, 524 (88%) were classified as having ATN. Their mean age was 58 years, 68% were male and 52% were surgical patients. The overall mortality rate was 62%. A total of 265 patients (51%) had ischaemic ATN, 201 (38%) had mixed ATN, and 58 (11%) had nephrotoxic ATN. There were no differences among groups in terms of age, sex, APACHE II score and reason for ICU admission. Multiple organ failure was more frequent among patients with ischaemic (46%) and mixed ATN (55%) than in those with nephrotoxic ATN (7%; P < 0.0001). The complications of acute renal failure (such as, gastrointestinal bleeding, acidosis, oliguria and hypervolaemia) were more prevalent in ischaemic and mixed ATN patients. Mortality was higher for ischaemic (66%; P = 0.001) and mixed ATN (63%; P = 0.0001) than for nephrotoxic ATN (38%). When ischaemic ATN patients, mixed ATN patients and all patients combined were analyzed by multivariate logistic regression, the independent factors for mortality identified were different except for oliguria, which was the only variable universally associated with death (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.64–5.49 [P = 0.0003] for ischaemic ATN; OR 1.96, 95% CI 1.04–3.68 [P = 0.036] for mixed ATN; and OR 2.53, 95% CI 1.60–3.76 [P < 0.001] for all patients combined]). Conclusion The frequency of isolated nephrotoxic ATN was low, with ischaemic and mixed ATN accounting for almost 90% of cases. The

  18. Acute tinnitus and permanent audiovestibular damage after hepatitis B vaccination.

    PubMed

    DeJonckere, P H; de Surgères, G G

    2001-01-01

    Yeast-derived recombinant DNA hepatitis B vaccine usage has been widely accepted since the early 1990s, especially for high-risk patients. Severe adverse effects have been reported infrequently. Certain neurological complications raise concern for hepatitis B vaccine: central nervous system demyelination, acute myelitis, acute cerebellar ataxia, and various peripheral mononeuropathies. Case reports on tinnitus, hearing loss, and vestibular damage are extremely scarce. The case presented here concerns a professionally active nurse, born in 1953, with a medical history of progressive renal failure and hemodialysis. Eleven hours after a second injection of the hepatitis B vaccine Engerix B, an acute left-sided tinnitus occurred and, a few hours later, severe left hearing loss and intense vertigo. Tinnitus and the sensation of vertigo regressed fairly quickly, but the hearing loss and the vestibular paresis were permanent. Increased interpeak intervals on auditory brain responses and lack of recruitment suggested that the lesion probably is located at the level of cranial nerve VIII. From a medicolegal point of view, this audiovestibular damage had to be considered an accident at work and not as an occupational disease.

  19. [Organ damage and cardiorenal syndrome in acute heart failure].

    PubMed

    Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

    2014-03-01

    Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome.

  20. [Definition and biomarkers of acute renal damage: new perspectives].

    PubMed

    Seijas, M; Baccino, C; Nin, N; Lorente, J A

    2014-01-01

    The RIFLE and AKIN criteria have definitely help out to draw attention to the relationship between a deterioration of renal function that produces a small increase in serum creatinine and a worse outcome. However, the specific clinical utility of using these criteria remains to be well-defined. It is believed that the main use of these criteria is for the design of epidemiological studies and clinical trials to define inclusion criteria and objectives of an intervention. AKI adopting term, re-summoning former ARF terminology, it is appropriate to describe the clinical condition characterized by damage to kidney, in the same way as the term is used to describe acute lung damage where the lung injury situation still has not increased to a situation of organ failure (dysfunction). The serum and urine biomarkers (creatinine, urea, and diuresis) currently in use are not sensitive or specific for detecting kidney damage, limiting treatment options and potentially compromising the outcome. New biomarkers are being studied in order to diagnose an earlier and more specific AKI, with the potential to change the definition criteria of AKI with different stages, currently based in diuresis and serum creatinine.

  1. Electrolyte Imbalances and Nephrocalcinosis in Acute Phosphate Poisoning on Chronic Type 1 Renal Tubular Acidosis due to Sjögren's Syndrome

    PubMed Central

    Cho, Sung-Gun; Han, Sang-Woong; Kim, Ho-Jung

    2013-01-01

    Although renal calcium crystal deposits (nephrocalcinosis) may occur in acute phosphate poisoning as well as type 1 renal tubular acidosis (RTA), hyperphosphatemic hypocalcemia is common in the former while normocalcemic hypokalemia is typical in the latter. Here, as a unique coexistence of these two seperated clinical entities, we report a 30-yr-old woman presenting with carpal spasm related to hypocalcemia (ionized calcium of 1.90 mM/L) due to acute phosphate poisoning after oral sodium phosphate bowel preparation, which resolved rapidly after calcium gluconate intravenously. Subsequently, type 1 RTA due to Sjögren's syndrome was unveiled by sustained hypokalemia (3.3 to 3.4 mEq/L), persistent alkaline urine pH (> 6.0) despite metabolic acidosis, and medullary nephrocalcinosis. Through this case report, the differential points of nephrocalcinosis and electrolyte imbalances between them are discussed, and focused more on diagnostic tests and managements of type 1 RTA. PMID:23400265

  2. Acute renal damage in infants after first urinary tract infection.

    PubMed

    Cascio, Salvatore; Chertin, Boris; Yoneda, Akihiro; Rolle, Udo; Kelleher, Jeremiah; Puri, Prem

    2002-07-01

    Urinary tract infection (UTI) is one of the most common causes of unexplained fever in neonates. The aim of this study was to determine the incidence of urinary tract anomalies and acute renal damage in neonates who presented with first urinary tract infection in the first 8 weeks of life. We reviewed the records of 95 infants, who were hospitalised with UTI during a 6-year period (1994-1999). Patients with antenatally diagnosed hydronephrosis and incomplete radiological investigations were excluded from the study. Of the remaining 57 patients, 42 were boys and 15 girls. The mean age at diagnosis was 32 days (range 5-60 days). All patients underwent renal ultrasonography (US), voiding cystourethrogram (VCUG) and (99m)Tc-dimercaptosuccinic acid (DMSA) scan. Urinary tract abnormalities were detected in 20 (35%) patients. Vesicoureteral reflux (VUR) was found in 19 (33%) neonates, 7 girls and 12 boys. Acute cortical defects on DMSA scan were present in 19 kidneys of patients with VUR and in 25 of those without reflux. Only one-third of neonates after first symptomatic UTI had VUR. We recommend that US, VCUG, and DMSA scan should be routinely performed after the first UTI in infants younger than 8 weeks.

  3. Acute sun damage and photoprotective responses in whales.

    PubMed

    Martinez-Levasseur, Laura M; Gendron, Diane; Knell, Rob J; O'Toole, Edel A; Singh, Manuraj; Acevedo-Whitehouse, Karina

    2011-05-22

    Rising levels of ultraviolet radiation (UVR) secondary to ozone depletion are an issue of concern for public health. Skin cancers and intraepidermal dysplasia are increasingly observed in individuals that undergo chronic or excessive sun exposure. Such alterations of skin integrity and function are well established for humans and laboratory animals, but remain unexplored for mammalian wildlife. However, effects are unlikely to be negligible, particularly for species such as whales, whose anatomical or life-history traits force them to experience continuous sun exposure. We conducted photographic and histological surveys of three seasonally sympatric whale species to investigate sunburn and photoprotection. We find that lesions commonly associated with acute severe sun damage in humans are widespread and that individuals with fewer melanocytes have more lesions and less apoptotic cells. This suggests that the pathways used to limit and resolve UVR-induced damage in humans are shared by whales and that darker pigmentation is advantageous to them. Furthermore, lesions increased significantly in time, as would be expected under increasing UV irradiance. Apoptosis and melanocyte proliferation mirror this trend, suggesting that whales are capable of quick photoprotective responses. We conclude that the thinning ozone layer may pose a risk to the health of whales and other vulnerable wildlife.

  4. Total Coumarins from Hydrangea paniculata Protect against Cisplatin-Induced Acute Kidney Damage in Mice by Suppressing Renal Inflammation and Apoptosis

    PubMed Central

    Jie, Ma; Jingzhi, Yang; Dongjie, Wang; Dongming, Zhang

    2017-01-01

    Aim. Hydrangea paniculata (HP) Sieb. is a medical herb which is widely distributed in southern China, and current study is to evaluate renal protective effect of aqueous extract of HP by cisplatin-induced acute kidney injury (AKI) in animal model and its underlying mechanisms. Materials and Methods. HP extract was prepared and the major ingredients were coumarin glycosides. AKI mouse models were established by single i.p. injection of 20 mg/kg cisplatin, and HP was orally administrated for total five times. The renal biochemical functions, pathological staining, kidney oxidative stress, and inflammatory status were measured. Apoptosis of tubular cells and infiltration of macrophages and neutrophils were also tested. Results. HP administration could improve the renal function by decreasing concentration of blood urea nitrogen (BUN) and creatinine and attenuates renal oxidative stress and tubular pathological injury and apoptosis; further research demonstrated that HP could inhibit the overproduction of proinflammatory cytokines and regulate caspase and BCL-2 family proteins. HP also reduced renal infiltration of macrophages and neutrophils, and its effect might be by downregulating phosphorylation of ERK1/2 and stat3 signaling pathway. Conclusions. This present study suggests that HP could ameliorate cisplatin induced kidney damage by antioxidation and suppressing renal inflammation and tubular cell apoptosis. PMID:28367225

  5. 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

  6. Acquired resistance to rechallenge injury in rats recovered from subclinical renal damage with uranyl acetate-Importance of proliferative activity of tubular cells

    SciTech Connect

    Sun, Yuan; Fujigaki, Yoshihide; Sakakima, Masanori; Hishida, Akira

    2010-02-15

    Animals recovered from acute renal failure are resistant to subsequent insult. We investigated whether rats recovered from mild proximal tubule (PT) injury without renal dysfunction (subclinical renal damage) acquire the same resistance. Rats 14 days after recovering from subclinical renal damage, which was induced by 0.2 mg/kg of uranyl acetate (UA) (sub-toxic dose), were rechallenged with 4 mg/kg of UA (nephrotoxic dose). Fate of PT cells and renal function were examined in response to nephrotoxic dose of UA. All divided cells after sub-toxic dose of UA insult were labeled with bromodeoxyuridine (BrdU) for 14 days then the number of PT cells with or without BrdU-labeling was counted following nephrotoxic dose of UA insult. Rats recovered from subclinical renal damage gained resistance to nephrotoxic dose of UA with reduced renal dysfunction, less severity of peak damage (necrotic and TUNEL+ apoptotic cells) and accelerated PT cell proliferation, but with earlier peak of PT damage. The decrease in number of PT cells in the early phase of rechallenge injury with nephrotoxic UA was more in rats pretreated with sub-toxic dose of UA than vehicle pretreated rats. The exaggerated loss of PT cells was mainly caused by the exaggerated loss of BrdU+ divided cells. In contrast, accelerated cell proliferation in rats recovered from sub-toxic dose of UA was observed mainly in BrdU- non-divided cells. The findings suggest that rats recovered from subclinical renal damage showed partial acquired resistance to nephrotoxic insult. Accelerated recovery with increased proliferative activity of non-divided PT cells after subclinical renal damage may mainly contribute to acquired resistance.

  7. Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

    PubMed

    Mukhopadhyay, Sanjay; Parambil, Joseph G

    2012-10-01

    Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF).

  8. 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.

  9. Methamphetamine causes acute hyperthermia-dependent liver damage.

    PubMed

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-10-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug.

  10. [Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitro].

    PubMed

    Bao, Yi-zhong; Wang, Dan; Hu, Yu-xing; Xu, Ai-hong; Sun, Mei-zhen; Chen, Hong-hong

    2011-11-01

    This study is to assess the efficacy of BPCBG on the decorporation of uranium (VI) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage. BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2. Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS. After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) oxidation. DTPA-CaNa3 was used as control. It was found that BPCBG at dosages of 60, 120, and 600 micromol kg(-1) resulted in 37%-61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%-31% and 86%-42% of uranium-treated group, respectively. After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%-60% of the intracellular uranium was removed by 10-250 micromol L(-1) of BPCBG. Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS. Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG and it could not protect uranium-induced cell damage. It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3. It could also

  11. Acute traumatic anterior glenohumeral dislocation complicated by axillary nerve damage: a case report

    PubMed Central

    Kazemi, Mohsen

    1998-01-01

    An elite soccer player presented with a classic acute anterior dislocation of the glenohumeral joint complicated by axillary nerve damage. The incidence, mechanism of injury, clinical presentation, conservative treatment and rehabilitation of the anterior glenohumeral joint dislocation and associated axillary nerve damage are discussed in this paper. ImagesFigure 3

  12. Papillary tubular adenoma with marked tubular vacuolization.

    PubMed

    Hattori, N; Imakado, S; Kikuchi, K; Murakami, T; Furue, M

    1997-12-01

    We report a case of papillary tubular adenoma, arising on the knee joint. The overall histologic structure of the tumor is consistent with that of papillary tubular adenoma with slight interluminal papillary changes, but most of the tumor cells present vacuolization outlined by carcinoembryonic antigen staining, suggesting that this adenoma may have resulted from microlumen formation. This is, to our knowledge, the first reported case of a papillary tubular adenoma with marked tubular vacuolization.

  13. 30-MM Tubular Projectile

    DTIC Science & Technology

    1984-10-01

    Suiza tubular projectile 20 9. Inspection of Hispano Suiza sabot 21 10. Inspection of GAU-8 sabot 22 11. Firing data - 30-rn tubular projectile (Hispano... Suiza 23 copper banded) 12. Firing data - 30-m tubular projectile (GAU-8 plastic 24 banded) 13. Firing data - 30-m tubular projectile (GAU-8 copper 25...42 13. In-flight Hispano Suiza tubular projectiles 43 14. In-flight C4U-8 (plastic) tubular projectile 44 15. In-flight GCU-8 (copper) tubular

  14. 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.

  15. Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion injury

    PubMed Central

    Maicas, Nuria; van der Vlag, Johan; Bublitz, Janin; Florquin, Sandrine; Bakker-van Bebber, Marinka; Dinarello, Charles A.; Verweij, Vivienne; Masereeuw, Roos; Joosten, Leo A.

    2017-01-01

    Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) monotherapy during the early and recovery phase of ischemia-induced acute kidney injury. Mild renal ischemia-reperfusion (I/R) injury was induced in male C57Bl/6 mice by bilateral clamping of the renal artery and vein for 20 min. hAAT (80 mg/kg, Prolastin®) was administered daily intraperitoneally (i.p.) from day -1 until day 7 after surgery. Control animals received the same amount of human serum albumin (hAlb). Plasma, urine and kidneys were collected at 2h, 1, 2, 3, 8 and 15 days after reperfusion for histological and biochemical analysis. hAAT partially preserved renal function and tubular integrity after induction of bilateral kidney I/R injury, which was accompanied with reduced renal influx of macrophages and a significant decrease of neutrophil gelatinase-associated lipocalin (NGAL) protein levels in urine and plasma. During the recovery phase, hAAT significantly decreased kidney injury molecule-1 (KIM-1) protein levels in urine but showed no significant effect on renal fibrosis. Although the observed effect size of hAAT administration was limited and therefore the clinical relevance of our findings should be evaluated carefully, these data support the potential of this natural protein to ameliorate ischemic and inflammatory conditions. PMID:28235038

  16. Chronicity following ischaemia-reperfusion injury depends on tubular-macrophage crosstalk involving two tubular cell-derived CSF-1R activators: CSF-1 and IL-34.

    PubMed

    Sanchez-Niño, Maria Dolores; Sanz, Ana Belen; Ortiz, Alberto

    2016-09-01

    Two structurally unrelated ligands activate the macrophage colony stimulating factor receptor (CSF-1R, c-fms, CD115): M-CSF/CSF-1 and interleukin-34 (IL-34). Both ligands promote macrophage proliferation, survival and differentiation. IL-34 also activates the protein-tyrosine phosphatase ζ receptor (PTP-ζ, PTPRZ1). Both receptors and cytokines are increased during acute kidney injury. While tubular cell-derived CSF-1 is required for kidney repair, Baek et al (J Clin Invest 2015; 125: 3198-3214) have now identified tubular epithelial cell-derived IL-34 as a promoter of kidney neutrophil and macrophage infiltration and tubular cell destruction during experimental kidney ischaemia-reperfusion, leading to chronic injury. IL-34 promoted proliferation of both intrarenal macrophages and bone marrow cells, increasing circulating neutrophils and monocytes and their kidney recruitment. Thus, injured tubular cells release two CSF-1R activators, one (CSF-1) that promotes tubular cell survival and kidney repair and another (IL-34) that promotes chronic kidney damage. These results hold promise for the development of IL-34-targeting strategies to prevent ischaemia-reperfusion kidney injury in contexts such as kidney transplantation. However, careful consideration should be given to the recent characterization by Bezie et al. (J Clin Invest 2015; 125: 3952-3964) of IL-34 as a T regulatory cell (Treg) cytokine that modulates macrophage responses so that IL-34-primed macrophages potentiate the immune suppressive capacity of Tregs and promote graft tolerance.

  17. Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage

    PubMed Central

    Mishima, Eikan; Inoue, Chisako; Saigusa, Daisuke; Inoue, Ryusuke; Ito, Koki; Suzuki, Yusuke; Jinno, Daisuke; Tsukui, Yuri; Akamatsu, Yosuke; Araki, Masatake; Araki, Kimi; Shimizu, Ritsuko; Shinke, Haruka; Suzuki, Takehiro; Takeuchi, Yoichi; Shima, Hisato; Akiyama, Yasutoshi; Toyohara, Takafumi; Suzuki, Chitose; Saiki, Yoshikatu; Tominaga, Teiji; Miyagi, Shigehito; Kawagisihi, Naoki; Soga, Tomoyoshi; Ohkubo, Takayoshi; Yamamura, Kenichi; Imai, Yutaka; Masuda, Satohiro; Sabbisetti, Venkata; Ichimura, Takaharu; Mount, David B.; Bonventre, Joseph V.; Ito, Sadayoshi; Tomioka, Yoshihisa; Itoh, Kunihiko

    2014-01-01

    Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis. PMID:24833129

  18. 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

  19. Renal Tubular Acidosis

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Renal Tubular Acidosis KidsHealth > For Parents > Renal Tubular Acidosis Print A A A What's in ... Causes Symptoms Diagnosis Treatment en español Acidosis tubular renal Each time our internal organs do something, such ...

  20. Evaluation of plasma von Willebrand factor as a biomarker for acute arterial damage in rats.

    PubMed

    Newsholme, S J; Thudium, D T; Gossett, K A; Watson, E S; Schwartz, L W

    2000-01-01

    Plasma von Willebrand factor (vWF) was evaluated as a potential biomarker of acute arterial damage in rats after a vasotoxic dose of the dopaminergic vasodilator, fenoldopam (FP). Male Sprague-Dawley rats were given FP or isotonic saline by subcutaneous injection, and plasma vWF was measured at 2, 6, and 24 hours after challenge. Mean plasma vWF values increased in FP-treated rats compared to controls at 2 hours (167 vs 122%; p < 0.05) and 6 hours postdose (172 vs 130%; p < 0.01) but were comparable to control values after 24 hours. Mesenteric arterial lesions were observed microscopically in all FP-treated rats 24 hours postdose but were not present in rats at 1, 2, 4, 6, or 8 hours after FP challenge. Further, plasma vWF concentrations increased in saline-treated rats after only the minimal perturbation of repeated venipuncture. These results indicate an early, minimal, and transient release of vWF that precedes the onset of morphologically evident vascular damage. The minimal increases in plasma vWF concentrations were of limited predictive value, may be more reflective of an acute-phase reactant response, and were not considered a reliable biomarker of acute FP-induced arterial damage in the rat.

  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. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

    PubMed Central

    la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

    2013-01-01

    OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

  3. Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress.

    PubMed

    Li, Qin; Bi, Ming Jun; Bi, Wei Kang; Kang, Hai; Yan, Le Jing; Guo, Yun-Liang

    2016-03-01

    Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO-1 and Nrf-2 proteins were found in normal brain tissue. CO poisoning could activate HO-1/Nrf-2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning.

  4. Blood Aggravates Histological and Functional Damage after Acute Subdural Hematoma in Rats.

    PubMed

    Jussen, Daniel; Krenzlin, Harald; Papaioannou, Chrysostomos; Ens, Swetlana; Kempski, Oliver; Alessandri, Beat

    2017-02-15

    Acute subdural hematoma (ASDH) is associated with high morbidity and mortality. Whether the volume effect of the hematoma and increase of intracranial pressure (ICP) or the local effect of blood are responsible for this severe pathophysiology is unclear. Therefore, we compared subdural infusion of autologous blood and paraffin oil in a rat model of ASDH. In a histological study, we investigated the effects on acute ICP, cerebral perfusion pressure (CPP), cerebral blood flow (CBF), tissue oxygen changes, and brain damage at 2, 24, and 96 h post-infusion. Inflammatory reaction was analyzed by immuno-staining for microglia (ionized calcium binding adaptor molecule 1 [Iba1]) and activated astrocytes (glial fibrillary acidic protein [GFAP]). Besides acute ICP and CBF changes, we investigated the development of behavior (neuroscore and beamwalk test) for up to 4 days after injury in a behavioral study. Despite comparably increased ICP, there was a more pronounced lesion growth in the blood infusion group during the first 96 h. Further, there was an increased peri-lesional immunoreactive area of Iba1 and GFAP 96 h post-infusion, primarily in the blood infusion group, whereas hippocampal damage was comparable in both infusion groups. In the behavioral evaluation, paraffin-infused animals showed a better recovery, compared with the blood infusion group. In conclusion, comparable acute time-course of ICP, CPP, and CBF clearly indicates that the differences in lesion size, inflammatory reaction, and behavioral deficits after blood- and paraffin oil-induced ASDH are partially due to blood constituents. Therefore, current data suggest that subdural hematomas should be completely removed as quickly as possible; decompression alone may not be sufficient to prevent secondary brain damage.

  5. Early detection of tubular dysfunction.

    PubMed

    Piscator, M

    1991-11-01

    The determination of low-molecular-weight proteins in urine as a tool for early detection of damage to the proximal tubules is briefly discussed. Beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin are at present the most widely used markers for tubular dysfunction. The determination of beta 2-microglobulin has earlier been the method of choice, but due to its instability at low pH there are certain disadvantages. Available data indicate that alpha 1-microglobulin may replace beta 2-microglobulin for screening purposes. The low-molecular-weight proteins are at present the best markers for early detection of tubular dysfunction; other constituents are not as well suited for this, even if the determination of urine enzymes has its supporters.

  6. Mechanism investigation of dioscin against CCl4-induced acute liver damage in mice.

    PubMed

    Lu, Binan; Xu, Yousong; Xu, Lina; Cong, Xiaonan; Yin, Lianhong; Li, Hua; Peng, Jinyong

    2012-09-01

    The mechanisms of the ameliorating effects of dioscin against CCl(4) induced acute liver damage are investigated in this study. Dioscin significantly inhibited (p<0.01) the increases of serum ALT and AST activities compared with the CCl(4)-treated animals. The hepatic lipid peroxidation formation and, concentrations of TNF-α and IL-6 were also decreased. Liver histopathologic studies and a DNA laddering assay indicated that dioscin protected hepatocytes against CCl(4)-induced apoptosis and necrosis. Furthermore, dioscin decreased the protein expressions of Fas/FasL, increased Bcl-2/Bax ratio, inhibited the release of cytochrome c from mitochondrion to cytosol and attenuated CCl(4)-induced caspase-3 and -8 activities. The expressions of ICAM-1, vimentin, prohibitin, HGF, c-MET and GSTA1 were also regulated by dioscin and iNOS was also involved in the effects of this agent. These protective effects against CCl(4) induced acute liver damage might be through inhibiting lipid peroxidation, inflammatory cytokines, necrosis and apoptosis, and dioscin shows promise for development toward the treatment of acute chemically mediated liver injury.

  7. Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans.

    PubMed

    Berzosa, C; Gómez-Trullén, E M; Piedrafita, E; Cebrián, I; Martínez-Ballarín, E; Miana-Mena, F J; Fuentes-Broto, L; García, J J

    2011-06-01

    Optimal levels of membrane fluidity are essential for numerous cell functions including cell growth, solute transport and signal transduction. Since exercise enhances free radical production, our aim was to evaluate in healthy male subjects the effects of an acute bout of maximal and submaximal exercise on the erythrocyte membrane fluidity and its possible relation to the oxidative damage overproduction due to exercise. Subjects (n = 34) performed three cycloergometric tests: a continuous progressive exercise, a strenuous exercise until exhaustion and an acute bout of exercise at an intensity corresponding to 70% of maximal work capacity for 30 min. Venous blood samples were collected before and immediately after these exercises. Erythrocyte membrane fluidity was assessed by fluorescence spectroscopy. Plasma malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl content of plasmatic proteins were used as an index of lipid and protein oxidation, respectively. Exercise produced a dramatic drop in the erythrocyte membrane fluidity as compared to resting time, but this was not accompanied by significant changes in the plasmatic MDA and 4-HDA concentrations. The highest erythrocyte membrane rigidity was detected immediately after strenuous exercise until exhaustion was performed. Protein carbonyl levels were higher after exhaustive exercises than at rest. Continuous progressive and strenuous exercises until exhaustion, but not submaximal workload, resulted in a significant enhanced accumulation of carbonylated proteins in the plasma. These findings are consistent with the idea that exercise exaggerates oxidative damage, which may contribute, at least partially, to explain the rigidity in the membrane of the erythrocytes due to acute exercise.

  8. Benchmark Dose Estimation for Cadmium-Induced Renal Tubular Damage among Environmental Cadmium-Exposed Women Aged 35–54 Years in Two Counties of China

    PubMed Central

    Hu, Jia; Li, Mei; Han, Tian-xu; Chen, Jian-wei; Ye, Lin-xiang; Wang, Qi; Zhou, Yi-kai

    2014-01-01

    Background A number of factors, including gender, age, smoking habits, and occupational exposure, affect the levels of urinary cadmium. Few studies have considered these influences when calculating the benchmark dose (BMD) of cadmium. In the present study, we aimed to calculate BMDs and their 95% lower confidence bounds (BMDLs) for cadmium-induced renal tubular effects in an age-specific population in south-central China. Methods In this study, urinary cadmium, β2-microglobulin, and N-acetyl-β-D-glucosaminidase levels were measured in morning urine samples from 490 randomly selected non-smoking women aged 35–54 years. Participants were selected using stratified cluster sampling in two counties (counties A and B) in China. Multiple regression and logistic regression analyses were used to investigate the dose-response relationship between urinary cadmium levels and tubular effects. BMDs/BMDLs corresponding to an additional risk (benchmark response) of 5% and 10% were calculated with assumed cut-off values of the 84th and 90th percentile of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase levels of the controls. Results Urinary levels of β2-microglobulin and N-acetyl-β-D-glucosaminidase increased significantly with increasing levels of urinary cadmium. Age was not associated with urinary cadmium levels, possibly because of the narrow age range included in this study. Based on urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase, BMDs and BMDLs of urinary cadmium ranged from 2.08 to 3.80 (1.41–2.18) µg/g cr for subjects in county A and from 0.99 to 3.34 (0.74–1.91) µg/g cr for those in county B. The predetermined benchmark response of 0.05 and the 90th percentiles of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase levels of the subjects not exposed to cadmium (i.e., the control group) served as cut-off values. Conclusions The obtained BMDs of urinary cadmium were similar to the reference point of 1 µg/g cr, as suggested by the

  9. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    PubMed

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one.

  10. Torsade de pointes indicates early neurologic damage in acute ischemic stroke.

    PubMed

    Huang, Li-Yen; Lin, Wei-Shiang; Lin, Wen-Yu; Cheng, Cheng-Chung; Cheng, Shu-Meng; Tsai, Tsung-Neng

    2013-12-01

    Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia that is related to QT prolongation. Although QT prolongation is commonly seen in acute stroke, TdP is rare. We report the case of a 78-year-old woman with ischemic stroke who presented with TdP as the initial manifestation of early neurologic deterioration. We hypothesized that an increase in intracranial pressure may result in neurohormonal activation, QT prolongation, and then myocardial damage, leading to TdP. We highlight that new onset of TdP in a patient with stroke may reflect neurologic deterioration, requiring further evaluation and specific intervention.

  11. Tubular organ epithelialisation

    PubMed Central

    Saksena, Rhea; Gao, Chuanyu; Wicox, Mathew; de Mel, Achala

    2016-01-01

    Hollow, tubular organs including oesophagus, trachea, stomach, intestine, bladder and urethra may require repair or replacement due to disease. Current treatment is considered an unmet clinical need, and tissue engineering strategies aim to overcome these by fabricating synthetic constructs as tissue replacements. Smart, functionalised synthetic materials can act as a scaffold base of an organ and multiple cell types, including stem cells can be used to repopulate these scaffolds to replace or repair the damaged or diseased organs. Epithelial cells have not yet completely shown to have efficacious cell–scaffold interactions or good functionality in artificial organs, thus limiting the success of tissue-engineered grafts. Epithelial cells play an essential part of respective organs to maintain their function. Without successful epithelialisation, hollow organs are liable to stenosis, collapse, extensive fibrosis and infection that limit patency. It is clear that the source of cells and physicochemical properties of scaffolds determine the successful epithelialisation. This article presents a review of tissue engineering studies on oesophagus, trachea, stomach, small intestine, bladder and urethral constructs conducted to actualise epithelialised grafts. PMID:28228931

  12. Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, acinar cell damage, and systemic inflammation in acute pancreatitis.

    PubMed

    Seyhun, Ersin; Malo, Antje; Schäfer, Claus; Moskaluk, Christopher A; Hoffmann, Ralf-Thorsten; Göke, Burkhard; Kubisch, Constanze H

    2011-11-01

    In acute pancreatitis, endoplasmic reticulum (ER) stress prompts an accumulation of malfolded proteins inside the ER, initiating the unfolded protein response (UPR). Because the ER chaperone tauroursodeoxycholic acid (TUDCA) is known to inhibit the UPR in vitro, this study examined the in vivo effects of TUDCA in an acute experimental pancreatitis model. Acute pancreatitis was induced in Wistar rats using caerulein, with or without prior TUDCA treatment. UPR components were analyzed, including chaperone binding protein (BiP), phosphorylated protein kinase-like ER kinase (pPERK), X-box binding protein (XBP)-1, phosphorylated c-Jun NH(2)-terminal kinase (pJNK), CCAAT/enhancer binding protein homologues protein, and caspase 12 and 3 activation. In addition, pancreatitis biomarkers were measured, such as serum amylase, trypsin activation, edema formation, histology, and the inflammatory reaction in pancreatic and lung tissue. TUDCA treatment reduced intracellular trypsin activation, edema formation, and cell damage, while leaving amylase levels unaltered. The activation of myeloperoxidase was clearly reduced in pancreas and lung. Furthermore, TUDCA prevented caerulein-induced BiP upregulation, reduced XBP-1 splicing, and caspase 12 and 3 activation. It accelerated the downregulation of pJNK. In controls without pancreatitis, TUDCA showed cytoprotective effects including pPERK signaling and activation of downstream targets. We concluded that ER stress responses activated in acute pancreatitis are grossly attenuated by TUDCA. The chaperone reduced the UPR and inhibited ER stress-associated proapoptotic pathways. TUDCA has a cytoprotective potential in the exocrine pancreas. These data hint at new perspectives for an employment of chemical chaperones, such as TUDCA, in prevention of acute pancreatitis.

  13. P53 inhibitor pifithrin-α prevents the renal tubular epithelial cells against injury

    PubMed Central

    Shen, Yun-Lin; Sun, Lei; Hu, Yu-Jie; Liu, Hua-Jie; Kuang, Xin-Yu; Niu, Xiao-Ling; Huang, Wen-Yan

    2016-01-01

    The injury and repair of renal tubular epithelial cells play an important role in the pathological process of acute kidney injury (AKI). This study aimed to clarify the role of cell cycle change in renal tubular epithelial cell injury and repair in vivo and in vitro. Sprague-Dawley rats received bilateral renal pedicle clamping for 45 min (ischemia) followed by reperfusion. Pifithrin-α, a p53 inhibitor, was administered at 24 h before renal ischemia and 3 and 14 days after reperfusion. Results showed the tubular epithelial cells in M phase increased significantly at 2 h to 72 h after ischemia/reperfusion (I/R), while pifithrin-α decreased them. Renal I/R caused renal tubular epithelial damage in rats, which was improved by pifithrin-α. The α-SMA mRNA expression was up-regulated significantly after I/R, while it was down-regulated by pifithrin-α.NRK-52E cells were cultured in vitro, cell damage was induced by addition of TNF-α, and then cells were treated with pifithrin-α. Cells treated with TNF-α alone in G2/M phase increased significantly, but they were reduced in the presence of pifithrin-α. In NRK-52E cells treated with pifithrin-α for 6 h, NGAL mRNA expression was significantly lower than in cells without pifithrin-α treatment. After NRK-52E cells were treated with pifithrin-α for 24 h, α-SMA and FN mRNA expression was significantly lower than in cells without the treatment. In summary, pifithrin-α can facilitate the progression of renal tubular epithelial cells through G2/M phase, protecting them against injury. PMID:27829991

  14. Proximal renal tubular acidosis

    MedlinePlus

    ... References Krapf R, Seldin DW, Alpern RJ. Clinical syndromes of metabolic acidosis. In: Alpern RJ, Caplan M, Moe OW, ... 529. Read More Distal renal tubular acidosis Fanconi syndrome Low potassium level Metabolic acidosis Osteomalacia Respiratory acidosis Rickets Review Date 10/ ...

  15. Distal renal tubular acidosis

    MedlinePlus

    ... get better with treatment. When to Contact a Medical Professional Call your health care provider if you have symptoms of distal renal tubular acidosis. Get medical help right away if you develop emergency symptoms ...

  16. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice

    PubMed Central

    Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  17. Ultrastructure damage of oviduct telocytes in rat model of acute salpingitis

    PubMed Central

    Yang, Jian; Chi, Chi; Liu, Zhen; Yang, Gang; Shen, Zong-Ji; Yang, Xiao-Jun

    2015-01-01

    Acute salpingitis (AS) is an inflammatory disease which causes severe damage to a subset of classically described cells lining in oviduct wall and contributes to interstitial fibrosis and fertility problems. Telocytes (TCs), a newly discovered peculiar type of stromal cells, have been identified in many organs, including oviduct, with proposed multiple potential bio-functions. However, with recent increasing reports regarding TCs alterations in disease-affected tissues, there is still lack of evidence about TCs involvement in AS-affected oviduct tissues and potential pathophysiological roles. We presently identified normal TCs by their characteristic ultrastructural features and immunophenotype. However, in AS-affected oviduct tissues, TCs displayed multiple ultrastructural damage both in cellular body and prolongations, with obvious loss of TCs and development of tissue fibrosis. Furthermore, TCs lose their interstitial 3-D network connected by homocellular or heterocellular junctions between TCs and adjacent cells. And especially, TCs connected to the activated immunocytes (mononuclear cells, eosinophils) and affected local immune state (repression or activation). Meanwhile, massive neutrophils infiltration and overproduced Inducible Nitric Oxide Synthase (iNOS), COX-2, suggested mechanism of inflammatory-induced TCs damage. Consequently, TCs damage might contribute to AS-induced structural and reproductive functional abnormalities of oviduct, probably via: (i) substances, energy and functional insufficiency, presumably, e.g. TC-specific genetic material profiles, ion channels, cytoskeletal elements, Tps dynamics, etc., (ii) impaired TCs-mediated multicellular signalling, such as homeostasis/angiogenesis, tissue repair/regeneration, neurotransmission, (iii) derangement of 3-D network and impaired mechanical support for TCs-mediated multicellular signals within the stromal compartment, consequently induced interstitial fibrosis, (iv) involvement in local

  18. Acute O 3 damage on first year coppice sprouts of aspen and maple sprouts in an open-air experiment.

    PubMed

    Darbah, Joseph N T; Jones, Wendy S; Burton, Andrew J; Nagy, John; Kubiske, Mark E

    2011-09-01

    We studied the effect of high ozone (O(3)) concentration (110-490 nmol mol(-1)) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O(3) pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O(3) exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O(3) and/or CO(2) for 12 years, were harvested. Acute O(3) damage was not uniform within the crowns of aspen suckers; it was most severe in the mature, fully expanded photosynthesizing leaves. Young expanding leaves showed no visible signs of acute O(3) damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O(3) damage as it directly controlled O(3) uptake. Maple sprouts, which had lower stomatal conductance, smaller stomatal aperture, higher stomatal density and larger leaf surface area, were tolerant of acute O(3) exposure. Moreover, elevated CO(2) did not ameliorate the adverse effects of acute O(3) dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O(3) levels.

  19. Acute O3 damage on first year coppice sprouts of aspen and maple sprouts in an open-air experiment

    SciTech Connect

    Darbah, J.N.; Nagy, J.; Jones, W. S.; Burton, A. J.; Kubiske, M. E.

    2011-10-01

    We studied the effect of high ozone (O{sub 3}) concentration (110-490 nmol mol{sup -1}) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O{sub 3} pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O{sub 3} exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O{sub 3} and/or CO{sub 2} for 12 years, were harvested. Acute O{sub 3} damage was not uniform within the crowns of aspen suckers; it was most severe in the mature, fully expanded photosynthesizing leaves. Young expanding leaves showed no visible signs of acute O{sub 3} damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O{sub 3} damage as it directly controlled O{sub 3} uptake. Maple sprouts, which had lower stomatal conductance, smaller stomatal aperture, higher stomatal density and larger leaf surface area, were tolerant of acute O{sub 3} exposure. Moreover, elevated CO{sub 2} did not ameliorate the adverse effects of acute O{sub 3} dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O{sub 3} levels.

  20. Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response

    PubMed Central

    Xing, Meichun; Wang, Xiaohui; Palmai-Pallag, Timea; Shen, Huahao; Helleday, Thomas; Hickson, Ian D.; Ying, Songmin

    2015-01-01

    The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81 is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity. PMID:26415217

  1. Acute DNA damage activates the tumour suppressor p53 to promote radiation-induced lymphoma

    PubMed Central

    Lee, Chang-Lung; Castle, Katherine D.; Moding, Everett J.; Blum, Jordan M.; Williams, Nerissa; Luo, Lixia; Ma, Yan; Borst, Luke B.; Kim, Yongbaek; Kirsch, David G.

    2015-01-01

    Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during cancer therapy ameliorates haematologic toxicity, whether it also impacts carcinogenesis remains unclear. Here we utilize a mouse model of inducible p53 short hairpin RNA (shRNA) to show that temporarily blocking p53 during total-body irradiation (TBI) not only ameliorates acute toxicity, but also improves long-term survival by preventing lymphoma development. Using KrasLA1 mice, we show that TBI promotes the expansion of a rare population of thymocytes that express oncogenic KrasG12D. However, blocking p53 during TBI significantly suppresses the expansion of KrasG12D-expressing thymocytes. Mechanistically, bone marrow transplant experiments demonstrate that TBI activates p53 to decrease the ability of bone marrow cells to suppress lymphoma development through a non-cell-autonomous mechanism. Together, our results demonstrate that the p53 response to acute DNA damage promotes the development of radiation-induced lymphoma. PMID:26399548

  2. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    PubMed Central

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

  3. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview

    PubMed Central

    Maléth, József; Hegyi, Péter

    2016-01-01

    Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30–50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca2+ overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca2+ signalling might be beneficial in AP. The inhibition of Ca2+ release from the endoplasmic reticulum or the activity of plasma membrane Ca2+ influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca2+ homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377719

  4. Acute protease supplementation effects on muscle damage and recovery across consecutive days of cycle racing.

    PubMed

    Shing, Cecilia M; Chong, Suzzen; Driller, Matthew W; Fell, James W

    2016-01-01

    Bromelain, a mixture of proteases obtained from pineapples, has been demonstrated to reduce exercise-induced muscle damage and inflammation, enhancing recovery. This investigation aimed to establish if markers of muscle damage and testosterone were influenced by acute bromelain supplementation in competitive cyclists taking part in a six-day cycle stage race. Fifteen highly trained cyclists [age: 22, [Formula: see text] = 1.2 years, height: 1.79, [Formula: see text] = 0.01 m, body mass: 68.69, [Formula: see text] = 1.97 kg] were supplemented with either bromelain (1000 mg·day(-1)) (n = 8) or a placebo (n = 7) across six days of competitive racing in a randomised, double-blind, placebo-controlled trial. Blood was collected from each cyclist on days one, three and six of racing and analysed for creatine kinase (CK), myoglobin, lactate dehydrogenase (LDH) and testosterone. CK activity (P < 0.001, d = 17.4-18.8), LDH activity (P < 0.004, d = 0.5-2.5) and myoglobin concentration (P < 0.007, d = 3.4-4.8) were elevated from pre-race on days three and six of racing in both groups. Testosterone concentrations were significantly lower on the final day of racing (P = 0.03, d = 1.3) and there was a trend for bromelain to maintain testosterone concentrations across the race period (P = 0.05, d = 1.04-1.70) when compared to placebo. Fatigue rating was lower in the bromelain group on day four of racing (P = 0.01). Consecutive days of competitive cycling were associated with increased markers of muscle damage and a reduction in circulating testosterone across the race period. Bromelain supplementation reduced subjective feelings of fatigue and was associated with a trend to maintain testosterone concentration.

  5. Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats

    PubMed Central

    Choi, Yoon Jeong; Kim, Nayoung; Lee, Ju Yup; Nam, Ryoung Hee; Seo, Ji Hyung; Lee, Seonmin; Kim, Hee Jin; Choi, Yoon Jin; Lee, Hye Seung; Lee, Dong Ho

    2016-01-01

    Background/Aims This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-l-cysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats. Methods Sprague-Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanol-only group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor α, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed. Results PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMK-S005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM. Conclusions These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes. PMID:26347516

  6. Acute damage threshold for infrared neural stimulation of the cochlea: functional and histological evaluation.

    PubMed

    Goyal, Vinay; Rajguru, Suhrud; Matic, Agnella I; Stock, Stuart R; Richter, Claus-Peter

    2012-11-01

    This article provides a mini review of the current state of infrared neural stimulation (INS), and new experimental results concerning INS damage thresholds. INS promises to be an attractive alternative for neural interfaces. With this method, one can attain spatially selective neural stimulation that is not possible with electrical stimulation. INS is based on the delivery of short laser pulses that result in a transient temperature increase in the tissue and depolarize the neurons. At a high stimulation rate and/or high pulse energy, the method bears the risk of thermal damage to the tissue from the instantaneous temperature increase or from potential accumulation of thermal energy. With the present study, we determined the injury thresholds in guinea pig cochleae for acute INS using functional measurements (compound action potentials) and histological evaluation. The selected laser parameters for INS were the wavelength (λ = 1,869 nm), the pulse duration (100 μs), the pulse repetition rate (250 Hz), and the radiant energy (0-127 μJ/pulse). For up to 5 hr of continuous irradiation at 250 Hz and at radiant energies up to 25 μJ/pulse, we did not observe any functional or histological damage in the cochlea. Functional loss was observed for energies above 25 μJ/pulse and the probability of injury to the target tissue resulting in functional loss increased with increasing radiant energy. Corresponding cochlear histology from control animals and animals exposed to 98 or 127 μJ/pulse at 250 Hz pulse repetition rate did not show a loss of spiral ganglion cells, hair cells, or other soft tissue structures of the organ of Corti. Light microscopy did not reveal any structural changes in the soft tissue either. Additionally, microcomputed tomography was used to visualize the placement of the optical fiber within the cochlea.

  7. Calpain inhibitor attenuated optic nerve damage in acute optic neuritis in rats

    PubMed Central

    Das, Arabinda; Guyton, M. Kelly; Smith, Amena; Wallace, Gerald; McDowell, Misty L.; Matzelle, Denise D.; Ray, Swapan K.; Banik, Naren L.

    2012-01-01

    Optic neuritis (ON), which is an acute inflammatory autoimmune demyelinating disease of the central nervous system (CNS), often occurs in multiple sclerosis (MS). ON is an early diagnostic sign in most MS patients caused by damage to the optic nerve leading to visual dysfunction. Various features of both MS and ON can be studied following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in Lewis rats. Inflammation and cell death in the optic nerve, with subsequent damage to the retinal ganglion cells in the retina, are thought to correlate with visual dysfunction. Thus, characterizing the pathophysiological changes that lead to visual dysfunction in EAE animals may help develop novel targets for therapeutic intervention. We treated EAE animals with and without the calpain inhibitor calpeptin (CP). Our studies demonstrated that the Ca2+-activated neutral protease calpain was upregulated in the optic nerve following induction of EAE at the onset of clinical signs (OCS) of the disease and these changes were attenuated following treatment with CP. These reductions correlated with decreases in inflammation (cytokines, iNOS, COX-2, NF-κB), and microgliosis (i.e. activated microglia). We observed that calpain inhibition reduced astrogliosis (reactive astroglia) and expression of aquaporin 4 (AQP4). The balance of Th1/Th2 cytokine production and also expression of the Th1-related CCR5 and CXCR3 chemokine receptors influence many pathological processes and play both causative and protective roles in neuron damage. Our data indicated that CP suppressed cytokine imbalances. Also, Bax:Bcl-2 ratio, production of tBid, PARP-1, expression and activities of calpain and caspases, and internucleosomal DNA fragmentation were attenuated after treatment with CP. Our results demonstrated that CP decreased demyelination [loss of myelin basic protein (MBP)] and axonal damage [increase in dephosphorylated neurofilament protein (de-NFP), and also

  8. DNA repair in ischemic acute kidney injury.

    PubMed

    Pressly, Jeffrey D; Park, Frank

    2017-04-01

    Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury leading to an induction of oxidative stress, cellular dysfunction, and loss of renal function. DNA damage, including oxidative base modifications and physical DNA strand breaks, is a consequence of renal IRI. Like many other organs in the body, a redundant and highly conserved set of endogenous repair pathways have evolved to selectively recognize the various types of cellular DNA damage and combat its negative effects on cell viability. Severe damage to the DNA, however, can trigger cell death and elimination of the injured tubular epithelial cells. In this minireview, we summarize the state of the current field of DNA damage and repair in the kidney and provide some expected and, in some cases, unexpected effects of IRI on DNA damage and repair in the kidney. These findings may be applicable to other forms of acute kidney injury and could provide new opportunities for renal research.

  9. 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

  10. Acute and chronic watercress supplementation attenuates exercise-induced peripheral mononuclear cell DNA damage and lipid peroxidation.

    PubMed

    Fogarty, Mark C; Hughes, Ciara M; Burke, George; Brown, John C; Davison, Gareth W

    2013-01-28

    Pharmacological antioxidant vitamins have previously been investigated for a prophylactic effect against exercise-induced oxidative stress. However, large doses are often required and may lead to a state of pro-oxidation and oxidative damage. Watercress contains an array of nutritional compounds such as β-carotene and α-tocopherol which may increase protection against exercise-induced oxidative stress. The present randomised controlled investigation was designed to test the hypothesis that acute (consumption 2 h before exercise) and chronic (8 weeks consumption) watercress supplementation can attenuate exercise-induced oxidative stress. A total of ten apparently healthy male subjects (age 23 (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited to complete the 8-week chronic watercress intervention period (and then 8 weeks of control, with no ingestion) of the experiment before crossing over in order to compete the single-dose acute phase (with control, no ingestion). Blood samples were taken at baseline (pre-supplementation), at rest (pre-exercise) and following exercise. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The main findings show an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases (P< 0.05 v. supplementation), while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H₂O₂ accumulation following exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid-soluble antioxidants (α-tocopherol, γ-tocopherol and xanthophyll) was observed following watercress supplementation (P< 0.05 v. control) in both experimental phases. These findings suggest that short- and long-term watercress ingestion has potential antioxidant effects against exercise-induced DNA damage and lipid peroxidation.

  11. Obatoclax potentiates the cytotoxic effect of cytarabine on acute myeloid leukemia cells by enhancing DNA damage.

    PubMed

    Xie, Chengzhi; Edwards, Holly; Caldwell, J Timothy; Wang, Guan; Taub, Jeffrey W; Ge, Yubin

    2015-02-01

    Resistance to cytarabine and anthracycline-based chemotherapy is a major cause of treatment failure for acute myeloid leukemia (AML) patients. Overexpression of Bcl-2, Bcl-xL, and/or Mcl-1 has been associated with chemoresistance in AML cell lines and with poor clinical outcome of AML patients. Thus, inhibitors of anti-apoptotic Bcl-2 family proteins could be novel therapeutic agents. In this study, we investigated how clinically achievable concentrations of obatoclax, a pan-Bcl-2 inhibitor, potentiate the antileukemic activity of cytarabine in AML cells. MTT assays in AML cell lines and diagnostic blasts, as well as flow cytometry analyses in AML cell lines revealed synergistic antileukemic activity between cytarabine and obatoclax. Bax activation was detected in the combined, but not the individual, drug treatments. This was accompanied by significantly increased loss of mitochondrial membrane potential. Most importantly, in AML cells treated with the combination, enhanced early induction of DNA double-strand breaks (DSBs) preceded a decrease of Mcl-1 levels, nuclear translocation of Bcl-2, Bcl-xL, and Mcl-1, and apoptosis. These results indicate that obatoclax enhances cytarabine-induced apoptosis by enhancing DNA DSBs. This novel mechanism provides compelling evidence for the clinical use of BH3 mimetics in combination with DNA-damaging agents in AML and possibly a broader range of malignancies.

  12. Inhibition of Ras signalling reduces neutrophil infiltration and tissue damage in severe acute pancreatitis.

    PubMed

    Yu, Changhui; Merza, Mohammed; Luo, Lingtao; Thorlacius, Henrik

    2015-01-05

    Neutrophil recruitment is known to be a rate-limiting step in mediating tissue injury in severe acute pancreatitis (AP). However, the signalling mechanisms controlling inflammation and organ damage in AP remain elusive. Herein, we examined the role of Ras signalling in AP. Male C57BL/6 mice were treated with a Ras inhibitor (farnesylthiosalicylic acid, FTS) before infusion of taurocholate into the pancreatic duct. Pancreatic and lung tissues as well as blood were collected 24 h after pancreatitis induction. Pretreatment with FTS decreased serum amylase levels by 82% and significantly attenuated acinar cell necrosis, tissue haemorrhage and oedema formation in taurocholate-induced pancreatitis. Inhibition of Ras signalling reduced myeloperoxidase (MPO) levels in the inflamed pancreas by 42%. In addition, administration of FTS decreased pancreatic levels of CXC chemokines as well as circulating levels of interleukin-6 and high-mobility group box 1 in animals exposed to taurocholate. Moreover, treatment with FTS reduced taurocholate-induced MPO levels in the lung. Inhibition of Ras signalling had no effect on neutrophil expression of Mac-1 in mice with pancreatitis. Moreover, FTS had no direct impact on trypsin activation in isolated pancreatic acinar cells. These results indicate that Ras signalling controls CXC chemokine formation, neutrophil recruitment and tissue injury in severe AP. Thus, our findings highlight a new signalling mechanism regulating neutrophil recruitment in the pancreas and suggest that inhibition of Ras signalling might be a useful strategy to attenuate local and systemic inflammation in severe AP.

  13. Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

    PubMed

    Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

    2014-11-01

    The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.

  14. Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage

    PubMed Central

    Rossi, S; Zanier, E; Mauri, I; Columbo, A; Stocchetti, N

    2001-01-01

    OBJECTIVES—To assess the frequency of hyperthermia in a population of acute neurosurgical patients; to assess the relation between brain temperature (ICT) and core temperature (Tc); to investigate the effect of changes in brain temperature on intracranial pressure (ICP).
METHODS—The study involved 20 patients (10 severe head injury, eight subarachnoid haemorrhage, two neoplasms) with median Glasgow coma score (GCS) 6. ICP and ICT were monitored by an intraventricular catheter coupled with a thermistor. Internal Tc was measured in the pulmonary artery by a Swan-Ganz catheter.
RESULTS—Mean ICT was 38.4 (SD 0.8) and mean Tc 38.1 (SD 0.8)°C; 73% of ICT and 57.5% of Tc measurements were ⩾38°C. The mean difference between ICT and Tc was 0.3 (SD 0.3)°C (range −0.7 to 2.3°C) (p=0. 0001). Only in 12% of patients was Tc higher than ICT. The main reason for the differences between ICT and Tc was body core temperature: the difference between ICT and Tc increased significantly with body core temperature and fell significantly when this was lowered. The mean gradient between ICT and Tc was 0.16 (SD 0.31)°C before febrile episodes (ICT being higher than Tc), and 0.41 (SD 0.38)°C at the febrile peak (p<0.05). When changes in temperature were considered, ICT had a profound influence on ICP. Increases in ICT were associated with a significant rise in ICP, from 14.9(SD 7.9) to 22 (SD 10.4) mm Hg (p<0.05). As the fever ebbed there was a significant decrease in ICP, from 17.5 (SD 8.62) to 16 (SD 7.76) mm Hg (p=0.02).
CONCLUSIONS—Fever is extremely frequent during acute cerebral damage and ICT is significantly higher than Tc. Moreover, Tc may underestimate ICT during the phases when temperature has the most impact on the intracranial system because of the close association between increases in ICT and ICP.

 PMID:11561026

  15. [Inherited tubular renal acidosis].

    PubMed

    Bouzidi, Hassan; Hayek, Donia; Nasr, Dhekra; Daudon, Michel; Fadhel Najjar, Mohamed

    2011-01-01

    Renal tubular acidosis (RTA) is a tubulopathy characterized by metabolic acidosis with normal anion gap secondary to abnormalities of renal acidification. RTA can be classified into four main subtypes: distal RTA, proximal RTA, combined proximal and distal RTA, and hyperkalemic RTA. Distal RTA (type 1) is caused by the defect of H(+) secretion in the distal tubules and is characterized by the inability to acidify the urine below pH 5.5 during systemic acidemia. Proximal RTA (type 2) is caused by an impairment of bicarbonate reabsorption in the proximal tubules and characterized by a decreased renal bicarbonate threshold. Combined proximal and distal RTA (type 3) secondary to a reduction in tubular reclamation of bicarbonate and an inability to acidify the urine in the face of severe acidemia. Hyperkalemic RTA (type 4) may occur as a result of aldosterone deficiency or tubular insensitivity to aldosterone. Clinicians should be alert to the presence of RTA in patients with an unexplained normal anion gap acidosis, hypokalemia, recurrent nephrolithiasis and nephrocalcinosis. The mainstay of treatment of RTA remains alkali replacement.

  16. Fueling the fire in acute kidney injury: endothelial cells collect their Toll.

    PubMed

    Sutton, Timothy A; Dagher, Pierre C

    2011-02-01

    Chen et al. demonstrate endothelial expression of Toll-like receptor 4 (TLR4) in the outer medulla of the kidney early in the course of ischemic acute kidney injury. Furthermore, they provide data that support the hypothesis that activation of endothelial TLR4 in the early extension phase of AKI by damage-associated molecular pattern molecules released from injured tubules results in endothelial activation. This activation can serve to amplify inflammation and tubular damage.

  17. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.

    PubMed

    de Bragança, Ana C; Volpini, Rildo A; Mehrotra, Purvi; Andrade, Lúcia; Basile, David P

    2016-07-01

    Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.

  18. Korean red ginseng ameliorates acute 3-nitropropionic acid-induced cochlear damage in mice.

    PubMed

    Tian, Chunjie; Kim, Young Ho; Kim, Young Chul; Park, Kyung Tae; Kim, Seung Won; Kim, Youn Ju; Lim, Hye Jin; Choung, Yun-Hoon

    2013-01-01

    3-Nitropropionic acid (3-NP), a mitochondrial toxin, has been reported to induce an acute cochlear damage. Korean red ginseng (KRG) is known to have protective effects from some types of hearing loss. This study aimed to observe the protective effect of KRG in an ototoxic animal model using 3-NP intratympanic injection. BALB/c mice were classified into 5 groups (n=15) and dose-dependent toxic effects after intratympanic injection with 3-NP (300-5000 mM) on the left ear were investigated to determine the appropriate toxicity level of 3-NP. For observation of the protective effects of KRG, 23 mice were grouped into 3-NP (500 mM, n=12) and KRG+3-NP groups (300 mg/kg KRG for 7 days before 500 mM 3-NP administration, n=11). Auditory brain response (ABR) and cochlear morphological evaluations were performed before and after drug administration. The ABR thresholds in the 800-5000 mM groups exceeded the maximum recording limit at 16 and 32 kHz 1 day after 3-NP administration. The ABR threshold in the 500 mM 3-NP+KRG group was significantly lower than that in the 500 mM 3-NP group from post 1 week to 1 month. The mean type II fibrocyte counts significantly differed between the control and 3-NP groups and between the 3-NP and 3-NP+KRG groups. Spiral ganglion cell degeneration in the 3-NP group was more severe than that in the 3-NP+KRG group. This animal model exhibited a dose-dependent hearing loss with histological changes. KRG administration ameliorated the deterioration of hearing by 3-NP.

  19. The acute toxicity of iron and copper: biomolecule oxidation and oxidative damage in rat liver.

    PubMed

    Boveris, Alberto; Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Torti, Horacio; Massot, Francisco; Repetto, Marisa G

    2012-11-01

    The transition metals iron (Fe) and copper (Cu) are needed at low levels for normal health and at higher levels they become toxic for humans and animals. The acute liver toxicity of Fe and Cu was studied in Sprague Dawley male rats (200 g) that received ip 0-60 mg/kg FeCl(2) or 0-30 mg/kg CuSO(4). Dose and time-responses were determined for spontaneous in situ liver chemiluminescence, phospholipid lipoperoxidation, protein oxidation and lipid soluble antioxidants. The doses linearly defined the tissue content of both metals. Liver chemiluminescence increased 4 times and 2 times after Fe and Cu overloads, with half maximal responses at contents (C(50%)) of 110 μgFe/g and 42 μgCu/g liver, and with half maximal time responses (t(1/2)) of 4h for both metals. Phospholipid peroxidation increased 4 and 1.8 times with C(50%) of 118 μg Fe/g and 45 μg Cu/g and with t(1/2) of 7h and 8h. Protein oxidation increased 1.6 times for Fe with C(50%) at 113 μg Fe/g and 1.2 times for Cu with 50 μg Cu/g and t(1/2) of 4h and 5h respectively. The accumulation of Fe and Cu in liver enhanced the rate of free radical reactions and produced oxidative damage. A similar free radical-mediated process, through the formation HO(•) and RO(•) by a Fenton-like homolytic scission of H(2)O(2) and ROOH, seems to operate as the chemical mechanism for the liver toxicity of both metals.

  20. Surgical Treatment of Tubular Breast Type II

    PubMed Central

    Dabizha, Oleksii Y.; Kostenko, Alona A.; Gomolyako, Irina V.; Samko, Kristina A.; Borovyk, Denys V.

    2016-01-01

    Background: Tubular breasts are caused by connective tissue malformation and occur in puberty. The main clinical characteristics of the tubular breast are breast asymmetry, dense fibrous ring around the areola, hernia bulging of the areola, megaareola, and hypoplasia of quadrants of the breast. Pathology causes great psychological discomfort to patients. Methods: This study included 17 patients, aged 18 to 34 years, with tubular breast type II who had bilateral pathology and were treated from 2013 to 2016. They had surgical treatment by method of the clinic. Correction technique consisted of mobilization of the central part of the gland and formation of a glandular flap with vertical and horizontal scorings, which looks like a “chessboard,” that was sufficient to cover the lower pole of the implant. The flap was fixed to the submammary folds with stitches that prevented its reduction and accented a new submammary fold. To underscore the importance of the method and to study the structural features of the vascular bed of tubular breast tissue, a morphological study was conducted. Results: Mean follow-up time was 25 months (range between 13 and 37 mo). The proposed technique achieved good results. Complications (hematoma, circumareolar scarring, and “double-bubble” deformity) were identified in 4 patients. Conclusions: Our morphological study confirmed that tubular breast tissue has increased vascularity due to the vessels with characteristic minor malformation and due to the high restorative potential of the vascular bed. Therefore, an extended glandular flap could be freely mobilized without damaging its blood supply; thus, the flap in most cases covered the implant completely and good aesthetic results were achieved. PMID:27826461

  1. 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.

  2. Protective effects of salusin-α and salusin-β on renal ischemia/reperfusion damage and their levels in ischemic acute renal failure.

    PubMed

    Cakir, M; Duzova, H; Taslidere, A; Orhan, G; Ozyalin, F

    2017-01-01

    Salusin-α and salusin-β are expressed in many tissues including the central nervous system, vessels and kidneys; they have been shown to decrease endoplasmic reticulum stress during heart ischemia/reperfusion (I/R) and to decrease apoptosis. We investigated the relation of salusin-α and salusin-β levels to acute ischemic renal failure. We also investigated whether these peptides are protective against renal I/R damage. Fifty-three rats were divided into six groups: control, I/R, I/R + salusin-α1, I/R + salusin-α10, I/R + salusin-β1 and I/R + salusin-β10. After removing the right kidney, the left kidney was subjected to ischemia for 1 h and reperfusion for 23 h. The treatment groups were injected subcutaneously at the beginning of ischemia with 1 or 10 μg/kg salusin-α, and 1 or 10 μg/kg salusin-β. Histopathology was assessed at the end of the experiment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) activity and malondialdehyde (MDA) levels were measured in the kidney tissue. Serum levels of blood urea nitrogen (BUN), creatinine (Cre), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) also were measured. Levels of salusin-α and salusin-β were measured in the serum and kidney tissues of the control and I/R groups. SOD, CAT and GSH-PX activities were decreased and the levels of MDA, TNF-α, IL-6, IL-1β, BUN and Cre were increased in the I/R group compared to controls. Severe glomerular and tubular damage was apparent in the I/R group compared to controls. The level of salusin-β was decreased in the serum and kidney tissue of the I/R group compared to controls, whereas the level of salusin-α was decreased in the serum and increased in the kidney tissue. Salusin-α and salusin-β administration increased SOD and GSH-PX enzyme activation and decreased the levels of MDA, TNF-α, IL-6 and IL-1β compared to the I/R group. BUN and Cre levels were decreased in the I/R + salusin-α1 group

  3. Suppression of the DNA damage response in acute myeloid leukemia versus myelodysplastic syndrome.

    PubMed

    Boehrer, S; Adès, L; Tajeddine, N; Hofmann, W K; Kriener, S; Bug, G; Ottmann, O G; Ruthardt, M; Galluzzi, L; Fouassier, C; Tailler, M; Olaussen, K A; Gardin, C; Eclache, V; de Botton, S; Thepot, S; Fenaux, P; Kroemer, G

    2009-06-04

    The molecular mechanisms responsible for the evolution from the preleukemic entities of low-risk myelodysplastic syndrome (MDS) to the less favorable forms of high-risk MDS, as well as those enabling transformation to acute myeloid leukemia (AML), are still incompletely understood. Abundant evidence from solid tumors demonstrates that preneoplastic lesions activate signaling pathways of a DNA damage response (DDR), which functions as an 'anticancer barrier' hindering tumorigenesis. Testing the hypothesis that subgroups of MDS and AML differ with respect to DDR, we first assessed markers of DDR (phosphorylation of ATM, Chk-1, Chk-2 and H2AX) in cell lines representing different entities of MDS (P39, MOLM-13) and AML (MV4-11, KG-1) before and after gamma-irradiation. Although gamma-irradiation induced apoptosis and G(2)/M arrest and a concomitant increase in the phosphorylation of ATM, Chk-1 and H2AX in MDS-derived cell lines, this radiation response was attenuated in the AML-derived cell lines. It is noteworthy that KG-1, but not P39 cells exhibit signs of an endogenous activation of the DDR. Similarly, we found that the frequency of P-ATM(+) cells detectable in bone marrow (BM) biopsies increased in samples from patients with AML as compared with high-risk MDS samples and significantly correlated with the percentage of BM blasts. In contrast, the frequency of gamma-H2AX(+) cells was heterogeneous in all subgroups of AML and MDS. Whereas intermediate-1 MDS samples contained as little P-Chk-1 and P-Chk-2 as healthy controls, staining for both checkpoint kinases increased in intermediate-2 and high-risk MDS, yet declined to near-to-background levels in AML samples. Thus the activation of Chk-1 and Chk-2 behaves in accord with the paradigm established for solid tumors, whereas ATM is activated during and beyond transformation. In conclusion, we demonstrate the heterogeneity of the DDR response in MDS and AML and provide evidence for its selective suppression in AML

  4. 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

  5. [Tubular renal acidosis].

    PubMed

    Seidowsky, A; Moulonguet-Doleris, L; Hanslik, T; Yattara, H; Ayari, H; Rouveix, E; Massy, Z A; Prinseau, J

    2014-01-01

    Renal tubular acidosis (RTAs) are a group of metabolic disorders characterized by metabolic acidosis with normal plasma anion gap. There are three main forms of RTA: a proximal RTA called type II and a distal RTA (type I and IV). The RTA type II is a consequence of the inability of the proximal tubule to reabsorb bicarbonate. The distal RTA is associated with the inability to excrete the daily acid load and may be associated with hyperkalaemia (type IV) or hypokalemia (type I). The most common etiology of RTA type IV is the hypoaldosteronism. The RTAs can be complicated by nephrocalcinosis and obstructive nephrolithiasis. Alkalinization is the cornerstone of treatment.

  6. [Neonatal hypoxic-ischemic nephropathy and urinary diagnostic indices: the utility of measuring tubular enzymes (NAG and AAP)].

    PubMed

    Bertotti, A; De Marchi, S; Brovedani, P; Gaeta, G; Peratoner, L; Mangiarotti, M A

    1990-01-01

    Feto-neonatal hypoxia can cause a functional kidney impairment, which is often temporary and not clinically overt, but sometimes leading to acute renal failure. Hypoxic stress may result in a tubulo-interstitial damage, and kidney tubular enzymes determination has proved to be an easy, early, and non invasive method to define a tubular interstitial lesion. A major target of nephrotoxicity is the proximal tubular cell: alterations in brush-border membrane and cytoplasm result in increased turnover processes in the kidney cortex, following by a corresponding increased excretion of alanine-aminopeptidase (AAP) and N-acetyl-glucosaminidase (NAG) from the proximal tubular cells, long before glomerular or tubular functions are impaired. AAP and NAG excretion is directly correlated with the strength and the duration of toxic alteration of the proximal tubule. NAG and AAP have been already studied in the adults and the children; they have been chosen for this investigation with a double aim: 1) to define the amount of their urinary excretion in relation with gestational age at birth; 2) to evaluate if in the newborn, independently of the gestational age, their urinary concentration may be increased by ischaemic conditions caused by hypoxia. We studied 52 healthy newborns (7 preterm of 33-36 weeks and 45 full-term) and 16 newborns with feto-neonatal hypoxia (8 preterm of 26-36 weeks and full-term) at the forth day of life. Urinary NAG and AAP were assayed by colorimetric methods and the results expressed as mU/mg. creatininuria.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Antioxidant and hepatoprotective effects of Schisandra chinensis pollen extract on CCl4-induced acute liver damage in mice.

    PubMed

    Cheng, Ni; Ren, Naiyan; Gao, Hui; Lei, Xingsheng; Zheng, Jianbin; Cao, Wei

    2013-05-01

    The aim of the present study was to investigate the antioxidant and hepatotective effects of Schisandra chinensis pollen extract (SCPE) on CCl4-induced acute liver damage in mice. Total phenolic content, total flavonoid content, individual phenolic compounds and antioxidant activities (1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, chelating activity, and reducing power assay) were determined. In vivo study, SCPE (10, 20 and 40g/kg) administered daily orally for 42days prior to CCl4-intoxicated. Our results showed that SCPE had high total phenolic content (53.74±1.21mg GAE/g), total flavonoid content (38.29±0.91mg Rutin/g), quercetin and hesperetin may be the major contributor to strong antioxidant activities. Moreover, SCPE significantly prevented the increase in serum ALT and AST level in acute liver damage induced by CCl4, decreased the extent of malondialdehyde (MDA) formation in liver and elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver. The results indicated that SCPE has strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl4, and have been supported by the evaluation of liver histopathology in mice. The hepatoprotective effect may be related to its free radical scavenging effect, increasing antioxidant activity and inhibiting lipid peroxidation.

  8. Effect of sesame oil against acetaminophen-induced acute oxidative hepatic damage in rats.

    PubMed

    Chandrasekaran, Victor Raj Mohan; Wan, Chang-Hsin; Liu, Li-Lian; Hsu, Dur-Zong; Liu, Ming-Yie

    2008-08-01

    Acetaminophen (APAP) overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of sesame oil on APAP-induced acute liver injury. Male Wistar rats were given APAP (1,000 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased aspartate transaminase, alanine transaminase, lipid peroxidation, and superoxide anion and hydroxyl radical generation levels; it also induced glutathione depletion. Sesame oil (8 mL/kg; orally) did not alter the gastric absorption of APAP, but it inhibited all the parameters altered by APAP and protected the rats against APAP-induced acute liver injury. We hypothesize that sesame oil maintained the intracellular glutathione levels, reduced reactive oxygen species levels, and inhibited lipid peroxidation in rats with APAP-induced acute liver injury.

  9. Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

    PubMed Central

    Yuvaraju, Priya; Beegam, Sumaya; Fahim, Mohamed A.; Ali, Badreldin H.

    2017-01-01

    CeO2 nanoparticles (CeO2 NPs) which are used as a diesel fuel additive are emitted in the particulate phase in the exhaust, posing a health concern. However, limited information exists regarding the in vivo acute toxicity of CeO2 NPs on multiple organs. Presently, we investigated the acute (24 h) effects of intratracheally instilled CeO2 NPs in mice (0.5 mg/kg) on oxidative stress, inflammation, and DNA damage in major organs including lung, heart, liver, kidneys, spleen, and brain. Lipid peroxidation measured by malondialdehyde production was increased in the lungs only, and reactive oxygen species were increased in the lung, heart, kidney, and brain. Superoxide dismutase activity was decreased in the lung, liver, and kidney, whereas glutathione increased in lung but it decreased in the kidney. Total nitric oxide was increased in the lung and spleen but it decreased in the heart. Tumour necrosis factor-α increased in all organs studied. Interleukin- (IL-) 6 increased in the lung, heart, liver, kidney, and spleen. IL-1β augmented in the lung, heart, kidney, and spleen. Moreover, CeO2 NPs induced DNA damage, assessed by COMET assay, in all organs studied. Collectively, these findings indicate that pulmonary exposure to CeO2 NPs causes oxidative stress, inflammation, and DNA damage in multiple organs. PMID:28392888

  10. Formation of a fibrin based gelatinous coat over repairing rat gastric epithelium after acute ethanol damage: interaction with adherent mucus.

    PubMed Central

    Sellers, L A; Allen, A; Bennett, M K

    1987-01-01

    A gelatinous coat, heterogeneous in appearance, was formed over damaged rat gastric mucosa recovering from acute ethanol injury. This coat, in places 1.6 mm thick (median thickness 680 microns), was 10 times thicker than the translucent layer of adherent mucus (median thickness 70 microns) covering the undamaged mucosa. Immunohistochemistry and periodic acid Schiff staining showed this gelatinous coat to be predominantly a fibrin gel with an exterior layer rich in mucus and necrotic cells. The plasma clotting time was significantly decreased in vitro by pig gastric mucus gel and soluble mucus glycoprotein (90% and 13% respectively) suggesting that in vivo the mucus layer remaining after epithelial damage could act as a template for fibrinogen-fibrin conversion. These results show that a fibrin based gelatinous coat, quite distinct from the adherent mucus layer and with considerable protective potential could be formed over the repairing rat gastric mucosa after acute ethanol damage. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:3653751

  11. Hyperhomocysteinemia Exacerbates Cisplatin-induced Acute Kidney Injury

    PubMed Central

    Long, Yanjun; Zhen, Xin; Zhu, Fengxin; Hu, Zheng; Lei, Wenjing; Li, Shuang; Zha, Yan; Nie, Jing

    2017-01-01

    Hyperhomocysteinemia (HHcy) has been linked to several clinical manifestations including chronic kidney disease. However, it is not known whether HHcy has a role in the development of acute kidney injury (AKI). In the present study, we reported that HHcy mice developed more severe renal injury after cisplatin injection and ischemia-reperfusion injury shown as more severe renal tubular damage and higher serum creatinine. In response to cisplatin, HHcy mice showed more prevalent tubular cell apoptosis and decreased tubular cell proliferation. Mechanistically, a heightened ER stress and a reduced Akt activity were observed in kidney tissues of HHcy mice after cisplatin injection. Stimulating cultured NRK-52E cells with Hcy significantly increased the fraction of cells in G2/M phase and cell apoptosis together with decreased Akt kinase activity. Akt agonist IGF-1 rescued HHcy-induced cell cycle arrest and cell apoptosis. In conclusion, the present study provides evidence that HHcy increases the sensitivity and severity of AKI. PMID:28255274

  12. Association of epithelial damage and signs of neutrophil mobilization in the airways during acute exacerbations of paediatric asthma

    PubMed Central

    Yoshihara, S; Yamada, Y; Abe, T; Lindén, A; Arisaka, O

    2006-01-01

    We examined whether epithelial damage is associated with mobilization of neutrophils or eosinophils in the airway lumen during acute exacerbations of paediatric asthma. Aspirated sputum samples were harvested from 65 paediatric patients (mean age 3·4 ± 0·4 years) during acute exacerbations of asthma. Patients with signs of infection were excluded. The presence of conglomerates of epithelial cells (i.e. ‘Creola bodies) in the aspirated sputum was utilized as a marker of epithelial damage. Among the paediatric asthma patients, 60% displayed Creola bodies (CrB+: n = 39) in their sputum samples whereas the remaining patients did not (CrB–: n = 26). CrB+ patients displayed more than a 20-fold increase in the concentration of the neutrophil-mobilizing cytokine interleukin (IL)-8 (pg/ml) and of the neutrophil product neutrophil elastase (NE, g/l), respectively, compared with CrB– patients (IL-8: 7468·2 ± 1953·6 versus 347·9 ± 72·6, P < 0·01; NE: 2072·4 ± 419·0 versus 438·5 ± 125·7, P < 0·01). Even though not statistically significant, a corresponding trend was observed for the relative number of sputum neutrophils. In contrast, the concentration of the eosinophil-mobilizing cytokine IL-5 and the esoinophil product ECP tended to be lower in CrB+ than in CrB– patients (P > 0·05). In conclusion, as indicated by the analysis of aspirated sputum, epithelial damage is associated with a locally enhanced chemotactic signal for and activity of neutrophils, but not eosinophils, during acute exacerbations of paediatric asthma. It remains to be determined whether these indirect signs of neutrophil mobilization in the airway lumen mirror an increased number of neutrophils in the surrounding airway tissue. PMID:16634793

  13. Triphasic multinutrient supplementation during acute resistance exercise improves session volume load and reduces muscle damage in strength-trained athletes.

    PubMed

    Bird, Stephen P; Mabon, Tom; Pryde, Mitchell; Feebrey, Sarah; Cannon, Jack

    2013-05-01

    We hypothesized that triphasic multinutrient supplementation during acute resistance exercise would enhance muscular performance, produce a more favorable anabolic profile, and reduce biochemical markers of muscle damage in strength-trained athletes. Fifteen male strength-trained athletes completed two acute lower-body resistance exercise sessions to fatigue 7 days apart. After a 4-hour fast, participants consumed either a multinutrient supplement (Musashi 1-2-3 Step System, Notting Hill, Australia) (SUPP) or placebo (PLA) beverage preexercise (PRE), during (DUR), and immediately postexercise (IP). Session volume loads were calculated as kilograms × repetitions. Lower-body peak power was measured using unloaded repeated countermovement jumps, and blood samples were collected to assess biochemistry, serum hormones, and muscle damage markers at PRE, DUR, IP, 30 minutes postexercise (P30), and 24 hours postexercise (P24h). The SUPP demonstrated increased glucose concentrations at DUR and IP compared with at PRE (P < .01), whereas PLA demonstrated higher glucose at P30 compared with at PRE (P < .001). Session volume load was higher for SUPP compared with PLA (P < .05). Cortisol increased at DUR, IP, and P30 compared with at PRE in both treatments (P < .05); however, SUPP also displayed lower cortisol at P24h compared with at PRE and PLA (P < .01). The total testosterone response to exercise was higher for PLA compared with SUPP (P < .01); however, total creatine kinase and C-reactive protein responses to exercise were lower for SUPP compared with PLA (P < .05). These data indicate that although triphasic multinutrient supplementation did not produce a more favorable anabolic profile, it improved acute resistance exercise performance while attenuating muscle damage in strength-trained athletes.

  14. Systematic analysis of axonal damage and inflammatory response in different white matter tracts of acutely injured rat spinal cord.

    PubMed

    Gomes-Leal, W; Corkill, D J; Picanço-Diniz, C W

    2005-12-20

    The mechanisms of white matter (WM) damage during secondary degeneration are a fundamental issue in the pathophysiology of central nervous system (CNS) diseases. Our main goal was to describe the pattern of an acute inflammatory response and secondary damage to axons in different WM tracts of acutely injured rat spinal cord. Adult rats were deeply anesthetized and injected with 20 nmol of NMDA into the spinal cord ventral horn on T7. Animals were perfused after survival times of 1 day, 3 days and 7 days. Ten micrometer sections were submitted to immunocytochemical analysis for activated macrophages/microglia, neutrophils and damaged axons. There were inflammatory response and progressive tissue destruction of ventral WM (VWM) with formation of microcysts in both VWM and lateral WM (LWM). In the VWM, the number of beta-amyloid precursor protein (beta-APP) end-bulbs increased from 1 day with a peak at 3 days, decreasing by 7 days following the injection. APP end-bulbs were present in the dorsal WM (DWM) at 3 days survival time but were not in the LWM. Electron microscopic analysis revealed different degrees of myelin disruption and axonal pathology in the vacuolated WM up to 14 mm along the rostrocaudal axis. Quantitative analysis revealed a significant loss of medium and large axons (P < 0.05), but not of small axons (P > 0.05). Our results suggest that bystander axonal damage and myelin vacuolation are important secondary component of the pathology of WM tracts following rat SCI. Further studies are needed to understand the mechanisms of these pathological events.

  15. 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.

  16. 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.

  17. 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.

  18. [Cutaneous damage after acute exposure to ionizing radiation: decisive for the prognosis of radiation accident victims].

    PubMed

    Dörr, H; Baier, T; Meineke, V

    2013-12-01

    The cutaneous radiation syndrome includes all deterministic effects on the skin and visible parts of the mucosa from ionizing radiation. The Intensity and duration of radiation-induced skin symptoms depend on the kind and quality of ionizing radiation. The aim of this study was the investigation of the importance of the time of the development of radiation induced-skin effects on the prognosis of radiation accident victims. Clinical data about radiation accident victims from the database SEARCH were used. 211 cases with good documentation regarding radiation-induced skin effects were selected. From these 211 patients, 166 survived the acute phase of the acute radiation syndrome, while 45 died during the acute phase. Among those patients who did not survive the acute phase, 82.2 % showed their first documented radiation-induced skin symptoms during the first 3 days after radiation exposure. Of those patients whose first documented radiation-induced skin symptoms appeared on or after day four, 94.2 % survived the acute phase. The time to the occurrence of the first radiation-induced skin effects is diagnostically significant. The skin plays an important role in the clinical course of radiation syndromes and in the development of radiation-induced multi-organ failure. In a retrospective data analysis like this, the quality of data might be a limitation.

  19. Inhibition of pancreatic oxidative damage by stilbene derivative dihydro-resveratrol: implication for treatment of acute pancreatitis

    PubMed Central

    Tsang, Siu Wai; Guan, Yi-Fu; Wang, Juan; Bian, Zhao-Xiang; Zhang, Hong-Jie

    2016-01-01

    Trans-resveratrol is a natural stilbenoid possessing multifarious pharmacological benefits; however, when orally consumed, it is rapidly metabolised by colonic microflora and converted to dihydro-resveratrol. Thus, this microbial metabolite is of great therapeutic relevance. In the present study, upon the oral administration of dihydro-resveratrol (10–50 mg/kg), the severity of acute pancreatitis in the cerulein-treated rats was significantly ameliorated as evidenced by decreased α-amylase activities in the plasma and lessened oedema formation in the pancreatic parenchyma. In addition, the generation of intracellular reactive oxidative products, including malondialdehyde and protein carbonyls, was accordingly reduced, so as the production of pro-inflammatory cytokines. While inhibiting the activities of NADPH oxidase and myeloperoxidase, the depletion of glutathione was considerably restored. Importantly, the attenuation of pancreatic oxidative damage by dihydro-resveratrol was associated with a down-regulation of the nuclear factor-kappaB and phosphatidylinositol 3′-kinase-serine/threonine kinase signalling pathways. Furthermore, we demonstrated that the solubility of dihydro-resveratrol was at least 5 times higher than trans-resveratrol whilst exhibiting a much lower cytotoxicity. Collectively, the current findings accentuate new mechanistic insight of dihydro-resveratrol in pancreatic oxidative damage, and advocate its therapeutic potential for the management of acute pancreatitis, particularly for patients unresponsive to trans-resveratrol due to the lack of proper microbial strains. PMID:26971398

  20. Inhibition of pancreatic oxidative damage by stilbene derivative dihydro-resveratrol: implication for treatment of acute pancreatitis.

    PubMed

    Tsang, Siu Wai; Guan, Yi-Fu; Wang, Juan; Bian, Zhao-Xiang; Zhang, Hong-Jie

    2016-03-14

    Trans-resveratrol is a natural stilbenoid possessing multifarious pharmacological benefits; however, when orally consumed, it is rapidly metabolised by colonic microflora and converted to dihydro-resveratrol. Thus, this microbial metabolite is of great therapeutic relevance. In the present study, upon the oral administration of dihydro-resveratrol (10-50 mg/kg), the severity of acute pancreatitis in the cerulein-treated rats was significantly ameliorated as evidenced by decreased α-amylase activities in the plasma and lessened oedema formation in the pancreatic parenchyma. In addition, the generation of intracellular reactive oxidative products, including malondialdehyde and protein carbonyls, was accordingly reduced, so as the production of pro-inflammatory cytokines. While inhibiting the activities of NADPH oxidase and myeloperoxidase, the depletion of glutathione was considerably restored. Importantly, the attenuation of pancreatic oxidative damage by dihydro-resveratrol was associated with a down-regulation of the nuclear factor-kappaB and phosphatidylinositol 3'-kinase-serine/threonine kinase signalling pathways. Furthermore, we demonstrated that the solubility of dihydro-resveratrol was at least 5 times higher than trans-resveratrol whilst exhibiting a much lower cytotoxicity. Collectively, the current findings accentuate new mechanistic insight of dihydro-resveratrol in pancreatic oxidative damage, and advocate its therapeutic potential for the management of acute pancreatitis, particularly for patients unresponsive to trans-resveratrol due to the lack of proper microbial strains.

  1. Urinary proteins of tubular origin: basic immunochemical and clinical aspects.

    PubMed

    Scherberich, J E

    1990-01-01

    A variety of tubular marker proteins, as compared to healthy controls, are excreted at an increased rate in the urine of patients with renal damage. Beside cytoplasmic glutathione-S-transferase and lysosomal beta-N-acetyl-glucosaminidase (beta-NAG) the majority of kidney-related urine proteins derives from membrane surface components of the most vulnerable proximal tubule epithelia, among them ala-(leu-gly)-aminopeptidase, gamma-glutamyl transpeptidase (GGT), the tubular portion of angiotensinase A, the major brush border glycoprotein 'SGP-240' and adenosine-deaminase-binding protein. Urinary tissue proteins, e.g. brush border (BB) microvilli, are immunologically identical with those antigens prepared from cell membranes of the human kidney itself. BB antigens are shed into the urine of patients with glomerulonephritis, interstitial nephritis, systemic diseases, e.g. systemic lupus erythematosus (SLE), diabetes mellitus and multiple myeloma, arterial hypertension, infectious diseases (malaria, AIDS) and after operations, renal grafting and administration of X-ray contrast media, aminoglycosides or certain cytostatics (cis-platinum). Tissue proteinuria of tubular proteins is determined by enzyme-kinetic or quantitative immunological assays applying either poly- or monoclonal antikidney antibodies. Clinical, ultrastructural and histochemical studies support the idea that both 'soluble' and high-molecular-weight membrane particles (vacuolar blebs, greater than 10(6) dalton) as well as microfilamental components of the epithelial cytoskeleton contribute to tubular 'histuria' which appears as a sensitive parameter in monitoring tubular damage under clinical conditions at a very early phase.

  2. [Clinical and immunological features of acute hepatitis B in patients with concomitant chronic toxic liver damage].

    PubMed

    Furyk, E; Ryabokon, E

    2013-02-01

    The article presents information obtained during the survey in 64 patients with acute hepatitis B. We show that acute hepatitis B in patients with concomitant chronic toxic liver characterized by a marked imbalance of cytokine status due to a lower level of interleukin-2 and a higher content of interleukin-8, the highest levels of nitrite content, spontaneous oxidative modifications of blood proteins and the lowest content of L -arginine in the blood serum in the dynamics of disease compared with patients without this concomitant factor. In the period of convalescence these changes in patients with acute hepatitis B with concomitant chronic toxic liver characterized combined with higher cytolysis of liver cells, often circulating in the blood of HBsAg seroconversion and less frequently with the advent of anti-HBeAg.

  3. SPARC (secreted protein acidic and rich in cysteine) knockdown protects mice from acute liver injury by reducing vascular endothelial cell damage

    PubMed Central

    Peixoto, E; Atorrasagasti, C; Aquino, JB; Militello, R; Bayo, J; Fiore, E; Piccioni, F; Salvatierra, E; Alaniz, L; García, MG; Bataller, R; Corrales, F; Gidekel, M; Podhajcer, O; Colombo, MI; Mazzolini, G

    2015-01-01

    Secreted protein, acidic and rich in cysteine (SPARC) is involved in many biological process including liver fibrogenesis, but its role in acute liver damage is unknown. To examine the role of SPARC in acute liver injury, we used SPARC knock-out (SPARC−/−) mice. Two models of acute liver damage were used: concanavalin A (Con A) and the agonistic anti-CD95 antibody Jo2. SPARC expression levels were analyzed in liver samples from patients with acute-on-chronic alcoholic hepatitis (AH). SPARC expression is increased on acute-on-chronic AH patients. Knockdown of SPARC decreased hepatic damage in the two models of liver injury. SPARC−/− mice showed a marked reduction in Con A-induced necroinflammation. Infiltration by CD4+ T cells, expression of tumor necrosis factor-α and interleukin-6 and apoptosis were attenuated in SPARC−/− mice. Sinusoidal endothelial cell monolayer was preserved and was less activated in Con A-treated SPARC−/− mice. SPARC knockdown reduced Con A-induced autophagy of cultured human microvascular endothelial cells (HMEC-1). Hepatic transcriptome analysis revealed several gene networks that may have a role in the attenuated liver damaged found in Con A-treated SPARC−/− mice. SPARC has a significant role in the development of Con A-induced severe liver injury. These results suggest that SPARC could represent a therapeutic target in acute liver injury. PMID:25410742

  4. Role of the glomerular-tubular imbalance with tubular predominance in the arterial hypertension pathophysiology.

    PubMed

    Fox, María Ofelia Barber; Gutiérrez, Ernesto Barber

    2013-09-01

    In previous investigations we caused renal tubular reabsorption preponderance relating to the glomerular filtration (Glomerular-tubular imbalance) and we observed that this fact conducted to volume expansion and development of arterial hypertension, in rats that previously were normotens. We based on this evidence and other which are reflected in the literature arrived at the following hypothesis: a greater proportion of tubular reabsorption relating to the filtered volume is the base of the establishment of the glomerular-tubular imbalance with tubular predominance (GTI-T), which favors to the Na(+)-fluid retention and volume expansion. All of which conduced to arterial hypertension. These facts explain a primary hypertensive role of the kidney, consistent with the results of renal transplants performed in different lines of hypertensive rats and their respective controls and in humans: hypertension can be transferred with the kidney. GTI-T aims to be, a common phenomenon involved in the hypertension development in the multiple ways which is manifested the hypertensive syndrome. In secondary hypertension, GTI-T is caused by significant disruptions of hormone secretions that control renal function, or obvious vascular or parenchymal damage of these organs. In primary hypertension the GTI-T has less obvious causes inherently developed in the kidney, including humoral, cellular and subcellular mechanisms, which may insidiously manifest under environmental factors influence, resulting in insidious development of hypertension. This would explain the state of prehypertension that these individuals suffer. So it has great importance to study GTI-T before the hypertension is established, because when hypertensive state is established, other mechanisms are installed and they contribute to maintain the hypertension. Our hypothesis may explaining the inability of the kidneys to excrete salt and water in hypertension, as Guyton and colleagues have expressed and constitutes a

  5. Mechanisms of renal tubular defects in old age.

    PubMed Central

    Dontas, A. S.; Marketos, S. G.; Papanayiotou, P.

    1972-01-01

    The mechanisms of renal tubular dysfunction in old age have been examined in twenty-eight clinically healthy elderly subjects without infection, and in fourteen subjects of similar age with laboratory evidence of intrarenal infection. The data were compared with those from thirteen clinically healthy young subjects. Studied were: proximal tubular (Tm(PAH)) and distal tubular (CH2O) activity, minimal and maximal osmolal U/P ratios, maximal osmolal excretion in hydropenia, and GFR levels under standard hydration and under water-loading. The reduction of GFR in old age is evident particularly in men under conditions of standard hydration: it is accentuated in the presence of renal infection. Proximal tubular activity is also significantly lower in elderly men, especially if they have chronic bacteriuria. The reduction is closely related to GFR levels, with identical Tm(PAH):C(in) ratios in all groups. This supports the intact nephron hypothesis for this part of the nephron. Distal tubular activity is depressed in old age in both sexes proportionately more than proximal tubular activity or the GFR. The lower CH2O: GFR ratios imply a selective distal tubular damage. Maximal osmolal U/P ratios in hydropenia are significantly higher in the young (mean 367) than in either the elderly non-infected (mean 279) or the elderly infected subjects (mean 212). Conversely, minimal U/P ratios in water-loading are lower in the young (mean 0.247) than in either elderly group (means 0.418 and 0.668). Osmolal excretion in hydropenia is not different between the groups, but urine flows in water-loading clearly separate them. The data indicate that simple functions of the distal-collecting tubule (e.g. the CH2O), are less affected in old age than are functions involving several medullary structures (as is the maximal U(osm) or U/P ratio). They suggest that the main impairment of the distal tubular cell involves the failure to achieve a proper osmotic gradient between tubular fluid and

  6. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    PubMed Central

    Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

    2008-01-01

    Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

  7. Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats.

    PubMed

    Huang, Jingyang; Liu, Baoyi; Yang, Chenghui; Chen, Haili; Eunice, Dzivor; Yuan, Zhongrui

    2013-10-16

    Hyperglycemia adversely affects the outcome of ischemic stroke. Extracellular HMGB1 plays a role in aggravating brain damage in the postischemic brain. The aim of this study was to determine whether the extracellular HMGB1 is involved in the worsened ischemic damage during hyperglycemic stroke. Male Wistar rats underwent middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Acute hyperglycemia was induced by an injection of 50% dextrose. Rats received glycyrrhizin, a specific HMGB1 inhibitor, or vehicle. HMGB-1 in cerebrospinal fluid and in brain parenchyma was detected at 2 or 4 h post-reperfusion. Neurological deficits, infarct volume and cerebral edema were assessed 24 h post-MCAO the disruption of blood-brain barrier (BBB) and the expression of tight junction protein Occludin were measured at 4 h post-reperfusion. Hyperglycemia enhanced the early release of HMGB1 from ischemic brain tissue, which was accompanied by increased infarct volume, neurological deficit, cerebral edema and BBB disruption. Glycyrrhizin alleviated the aggravation of infarct volume, neurological deficit, cerebral edema and BBB disruption by decreasing the degradation of tight junction protein Occludin in the ischemic hemisphere of hyperglycemic rats. In conclusion, enhanced early extracellular release of HMGB1 might represent an important mechanism for worsened ischemic damage, particularly early BBB disruption, during hyperglycemic stroke. An HMGB1 inhibitor glycyrrhizin is a potential therapeutic option for hyperglycemic stroke.

  8. Acute changes of serum markers for tissue damage after ESWL of kidney stones.

    PubMed

    Apostolov, I; Minkov, N; Koycheva, M; Isterkov, M; Abadjyev, M; Ondeva, V; Trendafilova, T

    1991-01-01

    Seventeen serum markers (including 9 enzyme activities) for eventual tissue damage were studied after ESWL in 40 patients with unilateral kidney calculosis. No changes were established in the 8 non-enzymic parameters and the activities of amylase, lipase, AST (GOT), ALT (GPT) and CK-MB. A statistically significant increase was found in LDH, alpha-HBDH, CK (twice) and glutamate dehydrogenase (3 times). The slight elevation of LDH and alpha-HBDH could be due to haemolysis caused by the shock waves. Increased activity of CK suggested myolysis and that of GlDH a hepatocellular damage.

  9. Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice

    PubMed Central

    Ringelstetter, Ashley; Khatib, Hasan; Abbott, David H.; Salih, Sana M.

    2015-01-01

    Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR) chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra) pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2–24 hours post-injection), Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished γH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR-treated females. While DXR significantly increased the “infertility index” (quantifying the percentage of dams failing to achieve pregnancy) through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health in a mouse

  10. [Complex etiology of acute renal failure in a newborn].

    PubMed

    Krzemień, Grazyna; Szmigielska, Agnieszka; Bieroza, Iwona; Roszkowska-Blaim, Maria

    2008-01-01

    Acute renal failure (ARF), which is diagnosed in 3.4-20% of newborns, is polyetiological in most cases. We present a newborn with non-oliguric ARF diagnosed in the first day of life, and caused by asphixia, intrauterine infection (IUI) and nephrotoxic effects of metotrexate treatment during pregnancy. Antibiotics, including netilmicin and vankomycin, were given because of IUI and infected central venous catheter. Dosage of drugs was adjusted to renal failure parameters, but monitoring of their serum levels was not available. It could cause augmented acute tubular necrosis and interstitial nephritis. Analysis of ARF risk factors in newborns helps in early diagnosis of renal damage and in prompt implementation of therapy.

  11. Curcumin counteracts cisplatin-induced nephrotoxicity by preventing renal tubular cell apoptosis.

    PubMed

    Topcu-Tarladacalisir, Yeter; Sapmaz-Metin, Melike; Karaca, Turan

    2016-11-01

    Curcumin has several biological functions particularly antioxidant and anti-inflammatory. The aims of this study are determination of the protective effects of curcumin on cisplatin-induced renal tubular cell apoptosis and related pathways in kidney. Eighteen male Wistar albino rats were randomly divided into three groups (n = 6): the control, cisplatin (CP), and cisplatin + curcumin (CP + CUR). Acute renal damage was induced by single dose of cisplatin (7.5 mg/kg) injected by intraperitoneally (i.p). The animals of curcumin-treated group were received daily 200 mg/kg curcumin per os (po), starting from 2 days before the injection of cisplatin to the day of sacrifice. Forty-eight hours after cisplatin injection, samples of cardiac blood and kidneys were harvested from the animals. In this study, the major finding is that curcumin treatment ameliorates the following conditions associated with cisplatin-induced nephrotoxicity: (1) the development of kidney injury (histopathology), (2) inflammatory responses [myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-10 levels], (3) the degree of lipid peroxidation [malondialdehyde (MDA) level], (4) renal tubular cell apoptosis (active caspase-3) and expression of related proteins [p53, Fas, and Fas ligand (Fas-L)] by immunohistochemistry, (5) renal dysfunction (serum urea and creatinine). In a conclusion, this study suggests that curcumin has antiapoptotic effect against cisplatin nephrotoxicity, in addition to anti-inflammatory and antioxidant properties.

  12. Lethal activity of FADD death domain in renal tubular epithelial cells.

    PubMed

    Justo, P; Sanz, A B; Lorz, C; Egido, J; Ortiz, A

    2006-06-01

    Fas-associated death domain (FADD) is an adaptor protein that is required for the transmission of the death signal from lethal receptors of the tumor necrosis factor superfamily. FADD contains a death domain (DD) and a death effector domain (DED). As death receptors contribute to renal tubular injury and tubular cell FADD increases in acute renal failure, we have studied the function of FADD in tubular epithelium. FADD expression was studied in kidney samples from mice. In order to study the contribution of FADD to renal tubular cell survival, FADD or FADD-DD were overexpressed in murine tubular epithelium. FADD is expressed in renal tubules of the healthy kidney. Both FADD and FADD-DD induce apoptosis in primary cultures of murine tubular epithelium and in the murine cortical tubular cell line. Death induced by FADD-DD has apoptotic morphology, but differs from death receptor-induced apoptosis in that it is not blocked by inhibitors of caspases. Neither an inhibitor of serine proteases nor overexpression of antiapoptotic BclxL prevented cell death. However, the combination of caspase and serine protease inhibition was protective. FADD and FADD-DD overexpression decreased nuclear factor kappa B activity. These data suggest that FADD has a death regulatory function in renal tubular cells that is independent of death receptors. FADD-DD is sufficient to induce apoptosis in these cells. This information is relevant to understanding the role of FADD in tubular injury.

  13. [Acute kidney failure during psoriasis therapy with fumaric acid derivatives].

    PubMed

    Dalhoff, K; Faerber, P; Arnholdt, H; Sack, K; Strubelt, O

    1990-06-29

    24 days after starting treatment of psoriasis with fumaric acid derivatives (0.8-1.0 g orally, plus unknown quantities locally) a 21-year-old woman developed acute oliguric renal failure with a rise of serum creatinine levels to 1094 mumol/l (12.4 mg/dl). Deterioration of renal function had been preceded by severe abdominal symptoms with nausea, vomiting and colicky pain. On admission to hospital she was dehydrated with hyponatraemia and hypokalaemia. There was glomerular microhaematuria, increased excretion of renal epithelia, and tubular proteinuria. Renal biopsy demonstrated acute tubular damage with vacuolization of proximal epithelia, dilated tubules and scattered necroses. After intermittent haemodialysis (13 courses over two weeks) renal function gradually recovered, as demonstrated at a follow-up examination four months after discharge.

  14. CXCL16 regulates cisplatin-induced acute kidney injury.

    PubMed

    Liang, Hua; Zhang, Zhengmao; He, Liqun; Wang, Yanlin

    2016-05-31

    The pathogenesis of cisplatin-induced acute kidney injury (AKI) is characterized by tubular cell apoptosis and inflammation. However, the molecular mechanisms are not fully understood. We found that CXCL16 was induced in renal tubular epithelial cells in response to cisplatin-induced AKI. Therefore, we investigated whether CXCL16 played a role in cisplatin-induced tubular cell apoptosis and inflammation. Wild-type and CXCL16 knockout mice were administrated with vehicle or cisplatin at 20 mg/kg by intraperitoneal injection. CXCL16 knockout mice had lower blood urea nitrogen and less tubular damage following cisplatin-induced AKI as compared with wild-type mice. Genetic disruption of CXCL16 reduced tubular epithelial cell apoptosis and decreased caspase-3 activation. Furthermore, CXCL16 deficiency inhibited infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was associated with reduced expression of the proinflammatory cytokines in the kidneys. Taken together, our results indicate that CXCL16 plays a crucial role in the pathogenesis of cisplatin-induced AKI through regulation of apoptosis and inflammation and maybe a novel therapeutic target for cisplatin-induced AKI.

  15. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    SciTech Connect

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  16. Hepatoprotective effect of Vitis vinifera L. leaves on carbon tetrachloride-induced acute liver damage in rats.

    PubMed

    Orhan, Didem Deliorman; Orhan, Nilüfer; Ergun, Ender; Ergun, Fatma

    2007-05-30

    The hepatoprotective effect of ethanolic extract and its four different fractions (CHCl(3), EtOAc, n-BuOH, and remaining water fraction) of Vitis vinifera L. leaves was investigated against carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. The ethanolic extract was found active at 125mg/kg dose (per os). The ethanolic extract was fractionated through successive solvent-solvent extractions and the n-BuOH fraction in 83mg/kg dose possessed remarkable antioxidant and hepatoprotective activities. Liver damage was assessed by using biochemical parameters (plasma and liver tissue MDA [malondialdehyde], transaminase enzyme levels in plasma [AST-aspartate transaminase, ALT-alanine transferase] and liver GSH [glutathione] levels). Additionally, the pathological changes in liver were evaluated by histopathological studies. Legalon 70 Protect was used as standard natural originated drug.

  17. Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

    PubMed

    Lehnert, Per; Johansson, Pär I; Ostrowski, Sisse R; Møller, Christian H; Bang, Lia E; Olsen, Peter Skov; Carlsen, Jørn

    2017-02-01

    Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

  18. Evaluating Radioprotective Effect of Hesperidin on Acute Radiation Damage in the Lung Tissue of Rats

    PubMed Central

    Rezaeyan, A.; Fardid, R.; Haddadi, G.H.; Takhshid, M.A.; Hosseinzadeh, M.; Najafi, M.; Salajegheh, A.

    2016-01-01

    Background: Oxidative stress plays an important role in the pathogenesis and progression of γ-irradiation-induced cellular damage, Lung is a radiosensitive organ and its damage is a dose-limiting factor in radiotherapy. The administration of dietary antioxidants has been suggested to protect against the succeeding tissue damage. The present study aimed to evaluate the radioprotective efficacy of Hesperidin (HES) against γ-irradiation-induced tissue damage in the lung of male rats. Materials and Methods: Thirty two rats were divided into four groups. Rats in Group 1 received PBS and underwent sham irradiation. Rats in Group 2 received HES and underwent sham irradiation. Rats in Group 3 received PBS and underwent γ-irradiation. Rats in Group 4 received HES and underwent γ-irradiation. These rats were exposed to γ-radiation 18 Gy using a single fraction cobalt-60 unit, and were administered HES (100 mg/kg/d, b.w, orally) for 7 days prior to irradiation. Rats in each group were sacrificed 24 hours after radiotherapy (RT) for the determination of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and histopathological evaluations. Results: Compared to group 1, the level of SOD and GSH significantly decreased and MDA level significantly increased in group 3 at 24 h following irradiation, (p=0.001, p<0.001, p=0.001), respectively. A statistically significant difference in all parameters was observed for rats in group 4 as compared to group 3 (p<0.05). Histopathological results 24 hours after RT showed that radiation has increased inflammation, lymphocyte, macrophage and neutrophil compared to group 1 ( p<0.0125). Oral administration of HES before RT significantly decreased macrophage and neutrophil when compared to group 3 (p<0.0125), but partly there was inflammation and lymphocyte that indicated there was no significant difference when compared to group 3 (p>0.0125). Conclusion: Oral administration of HES was found to offer protection against

  19. Acute Oxidative Effect and Muscle Damage after a Maximum 4 Min Test in High Performance Athletes.

    PubMed

    Ferreira, Heros Ribeiro; Ferreira, Pamela Gill; Loures, João Paulo; Fernandes Filho, José; Fernandes, Luiz Cláudio; Buck, Hudson Sousa; Montor, Wagner Ricardo

    2016-01-01

    The purpose of this investigation was to determine lipid peroxidation markers, physiological stress and muscle damage in elite kayakers in response to a maximum 4-min kayak ergometer test (KE test), and possible correlations with individual 1000m kayaking performances. The sample consisted of twenty-three adult male and nine adult female elite kayakers, with more than three years' experience in international events, who voluntarily took part in this study. The subjects performed a 10-min warm-up, followed by a 2-min passive interval, before starting the test itself, which consisted of a maximum 4-min work paddling on an ergometer; right after the end of the test, an 8 ml blood sample was collected for analysis. 72 hours after the test, all athletes took part in an official race, when then it was possible to check their performance in the on site K1 1000m test (P1000m). The results showed that all lipoproteins and hematological parameters tested presented a significant difference (p≤0.05) after exercise for both genders. In addition, parameters related to muscle damage such as lactate dehydrogenase (LDH) and creatine kinase (CK) presented significant differences after stress. Uric acid presented an inverse correlation with the performance (r = -0.76), while CK presented a positive correlation (r = 0.46) with it. Based on these results, it was possible to verify muscle damage and the level of oxidative stress caused by indoor training with specific ergometers for speed kayaking, highlighting the importance of analyzing and getting to know the physiological responses to this type of training, in order to provide information to coaches and optimize athletic performance.

  20. Acute Oxidative Effect and Muscle Damage after a Maximum 4 Min Test in High Performance Athletes

    PubMed Central

    Fernandes Filho, José; Fernandes, Luiz Cláudio

    2016-01-01

    The purpose of this investigation was to determine lipid peroxidation markers, physiological stress and muscle damage in elite kayakers in response to a maximum 4-min kayak ergometer test (KE test), and possible correlations with individual 1000m kayaking performances. The sample consisted of twenty-three adult male and nine adult female elite kayakers, with more than three years’ experience in international events, who voluntarily took part in this study. The subjects performed a 10-min warm-up, followed by a 2-min passive interval, before starting the test itself, which consisted of a maximum 4-min work paddling on an ergometer; right after the end of the test, an 8 ml blood sample was collected for analysis. 72 hours after the test, all athletes took part in an official race, when then it was possible to check their performance in the on site K1 1000m test (P1000m). The results showed that all lipoproteins and hematological parameters tested presented a significant difference (p≤0.05) after exercise for both genders. In addition, parameters related to muscle damage such as lactate dehydrogenase (LDH) and creatine kinase (CK) presented significant differences after stress. Uric acid presented an inverse correlation with the performance (r = -0.76), while CK presented a positive correlation (r = 0.46) with it. Based on these results, it was possible to verify muscle damage and the level of oxidative stress caused by indoor training with specific ergometers for speed kayaking, highlighting the importance of analyzing and getting to know the physiological responses to this type of training, in order to provide information to coaches and optimize athletic performance. PMID:27111088

  1. Myocardial changes in acute Trypanosoma cruzi infection. Ultrastructural evidence of immune damage and the role of microangiopathy.

    PubMed Central

    Andrade, Z. A.; Andrade, S. G.; Correa, R.; Sadigursky, M.; Ferrans, V. J.

    1994-01-01

    Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:8203476

  2. Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia

    PubMed Central

    Zhang, Xuezhong; Wang, Nan; Tan, Jing; Fang, Xianhai; Wang, Qi; Tao, Tao; Li, Wenzhi

    2016-01-01

    Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA) ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30–39 mmHg, 40–49 mmHg, 50–59 mmHg, and 60–69 mmHg, respectively) or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60–80 mmHg) for 180 min. The mean artery pressure (MAP), blood gas, and cerebral blood flow (CBF) were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4) expression. In rats treated with severe hypoxia (PaO2 < 50 mmHg), hypercapnia augmented the decline of MAP with cortical CBF and damaged blood–brain barrier permeability (p < 0.05). In contrast, in rats treated with mild to moderate hypoxia (PaO2 > 50 mmHg), hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg); especially under mild hypoxemia (PaO2 > 60 mmHg), hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05). Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental

  3. Indicators of Acute and Persistent Renal Damage in Adult Thrombotic Microangiopathy

    PubMed Central

    Sucker, Christoph; Kuhr, Kathrin; Hollenbeck, Markus; Hetzel, Gerd R.; Burst, Volker; Teschner, Sven; Rump, Lars C.; Benzing, Thomas; Grabensee, Bernd; Kurschat, Christine E.

    2012-01-01

    Background Thrombotic microangiopathies (TMA) in adults such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are life-threatening disorders if untreated. Clinical presentation is highly variable and prognostic factors for clinical course and outcome are not well established. Methods We performed a retrospective observational study of 62 patients with TMA, 22 males and 40 females aged 16 to 76 years, treated with plasma exchange at one center to identify clinical risk factors for the development of renal insufficiency. Results On admission, 39 of 62 patients (63%) had acute renal failure (ARF) with 32 patients (52%) requiring dialysis treatment. High systolic arterial pressure (SAP, p = 0.009) or mean arterial pressure (MAP, p = 0.027) on admission was associated with acute renal failure. Patients with SAP>140 mmHg on admission had a sevenfold increased risk of severe kidney disease (OR 7.464, CI 2.097–26.565). MAP>100 mmHg indicated a fourfold increased risk for acute renal failure (OR 4.261, CI 1.400–12.972). High SAP, diastolic arterial pressure (DAP), and MAP on admission were also independent risk factors for persistent renal insufficiency with the strongest correlation for high MAP. Moreover, a high C-reactive protein (CRP) level on admission correlated with renal failure in the course of the disease (p = 0.003). At discharge, renal function in 11 of 39 patients (28%) had fully recovered, 14 patients (23%) remained on dialysis, and 14 patients (23%) had non-dialysis-dependent chronic kidney disease. Seven patients (11%) died. We identified an older age as risk factor for death. Conclusions High blood pressure as well as high CRP serum levels on admission are associated with renal insufficiency in TMA. High blood pressure on admission is also a strong predictor of sustained renal insufficiency. Thus, adult TMA patients with high blood pressure may require special attention to prevent persistent renal failure

  4. Spores of Aspergillus versicolor isolated from indoor air of a moisture-damaged building provoke acute inflammation in mouse lungs.

    PubMed

    Jussila, Juha; Komulainen, Hannu; Kosma, Veli-Matti; Nevalainen, Aino; Pelkonen, Jukka; Hirvonen, Maija-Riitta

    2002-12-01

    Microbial growth in moisture-damaged buildings has been associated with respiratory health effects, and the spores of the mycotoxin producing fungus Aspergillus versicolor are frequently present in the indoor air. To characterize the potential of these spores to cause harmful respiratory effects, mice were exposed via intratracheal instillation to a single dose of the spores of A. versicolor (1 x 10(5), 1 x 10(6), 5 x 10(6), 1 x 10(7), or 1 x 10(8) spores), isolated from the indoor air of a moisture-damaged building. Inflammation and toxicity in lungs were evaluated 24 h later by assessment of biochemical markers and histopathology. The time course of the effects was investigated with the dose of 5 x 10(6) spores for up to 28 days. The exposure to the spores increased transiently proinflammatory cytokine levels (tumor necrosis factor [TNF] alpha and interleukin [IL]-6) in bronchoalveolar lavage fluid (BALF). The cytokine responses were dose and time dependent. The highest cytokine concentrations were measured at 6 h after the dose, and they returned to the control level by 3 days. Moreover, the spores of A. versicolor recruited inflammatory cells into airways: Neutrophils peaked transiently at 24 h, macrophages at 3 days, and lymphocytes at 7 days after the dosing. The inflammatory cell response did not completely disappear during the subsequent 28 days, though no histopathological changes were seen at that time point. The spores did not induce expression of inducible nitric oxide synthase in lavaged cells. Only the highest spore dose (1 x 10(8)) markedly increased serum IL-6, increased vascular leakage, and caused cytotoxicity (i.e., increased levels of albumin, total protein, lactate dehydrogenase [LDH], and hemoglobin in BALF) in the airways. In summary, the spores of A. versicolor caused acute inflammation in mouse lungs. This indicates that they have potential to provoke adverse health effects in the occupants of moisture-damaged buildings.

  5. The acute response of pericytes to muscle-damaging eccentric contraction and protein supplementation in human skeletal muscle.

    PubMed

    De Lisio, Michael; Farup, Jean; Sukiennik, Richard A; Clevenger, Nicole; Nallabelli, Julian; Nelson, Brett; Ryan, Kelly; Rahbek, Stine K; de Paoli, Frank; Vissing, Kristian; Boppart, Marni D

    2015-10-15

    Skeletal muscle pericytes increase in quantity following eccentric exercise (ECC) and contribute to myofiber repair and adaptation in mice. The purpose of the present investigation was to examine pericyte quantity in response to muscle-damaging ECC and protein supplementation in human skeletal muscle. Male subjects were divided into protein supplement (WHY; n = 12) or isocaloric placebo (CHO; n = 12) groups and completed ECC using an isokinetic dynamometer. Supplements were consumed 3 times/day throughout the experimental time course. Biopsies were collected prior to (PRE) and 3, 24, 48, and 168 h following ECC. Reflective of the damaging protocol, integrin subunits, including α7, β1A, and β1D, increased (3.8-fold, 3.6-fold and 3.9-fold, respectively, P < 0.01) 24 h post-ECC with no difference between supplements. Pericyte quantity did not change post-ECC. WHY resulted in a small, but significant, decrease in ALP(+) pericytes when expressed as a percentage of myonuclei (CHO 6.8 ± 0.3% vs. WHY 5.8 ± 0.3%, P < 0.05) or per myofiber (CHO 0.119 ± 0.01 vs. WHY 0.098 ± 0.01, P < 0.05). The quantity of myonuclei expressing serum response factor and the number of pericytes expressing serum response factor, did not differ as a function of time post-ECC or supplement. These data demonstrate that acute muscle-damaging ECC increases α7β1 integrin content in human muscle, yet pericyte quantity is largely unaltered. Future studies should focus on the capacity for ECC to influence pericyte function, specifically paracrine factor release as a mechanism toward pericyte contribution to repair and adaptation postexercise.

  6. Physiological pH. Effects on posthypoxic proximal tubular injury.

    PubMed

    Zager, R A; Schimpf, B A; Gmur, D J

    1993-04-01

    After O2 deprivation, tissue acidosis rapidly self-corrects. This study assessed the effect of this pH correction on the induction, and pathways, of posthypoxic proximal tubular injury. In addition, ways to prevent the resultant injury were explored. Isolated rat proximal tubular segments (PTSs) were subjected to hypoxia/reoxygenation (50/30 or 30/50 minutes) under the following incubation conditions: 1) continuous pH 7.4, 2) continuous pH 6.8, or 3) hypoxia at pH 6.8 and reoxygenation at pH 7.4 (NaHCO3 or Tris base addition). Continuously oxygenated PTSs maintained under these same pH conditions served as controls. Lethal cell injury was assessed by lactate dehydrogenase (LDH) release. pH effects on several purported pathways of hypoxia/reoxygenation injury were also assessed (ATP depletion, lipid peroxidation, and membrane deacylation). Acidosis blocked hypoxic LDH release (pH 7.4, 50 +/- 2%; pH 6.8, 6 +/- 1%) without mitigating membrane deacylation or ATP depletion. During reoxygenation, minimal LDH was released (3-5%) if pH was held constant. However, if posthypoxic pH was corrected, immediate (< or = 5 minutes) and marked cell death (e.g., 55 +/- 3% with Tris) occurred. This was dissociated from lipid peroxidation or new deacylation, and it was preceded by a depressed ATP/ADP ratio (suggesting an acidosis-associated defect in hypoxic/posthypoxic cell energetics). Realkalinization injury was not inevitable, since it could be substantially blocked by 1) posthypoxic glycine addition, 2) transient posthypoxic hypothermia, or 3) allowing a 10-minute reoxygenation (cell recovery) period before base addition. Neither mannitol nor graded buffer Ca2+ deletion conferred protection. Acute pH correction caused no injury to continuously oxygenated PTSs. Conclusions are as follows: 1) Posthypoxic "pH shock" causes virtually immediate cell death, not by causing de novo injury but, rather, by removing the cytoprotective effect of acidosis. 2) This injury can be prevented by a

  7. Renal tubular function in hyperparathyroidism.

    PubMed Central

    van 't Hoff, W.; Bicknell, E. J.

    1989-01-01

    Renal tubular function was assessed in a group of patients with mild hyperparathyroidism before and after a mean period of 2.7 years conservative management. It was also assessed, before and after a mean of 3.3 years following surgery in a group of patients with initially higher plasma calcium concentration. Mean maximum urine osmolality was within the accepted range as was the maximum urine plasma hydrogen ion gradient in both groups at the time of diagnosis. No significant change in renal tubular function was observed in either group over the periods of this study. Although deterioration after a long period cannot be excluded, we do not consider that regular assessment of renal tubular function is necessary in the conservative management of primary hyperparathyroidism. PMID:2616415

  8. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF

    NASA Astrophysics Data System (ADS)

    Adibzadeh, F.; van Rhoon, G. C.; Verduijn, G. M.; Naus-Postema, N. C.; Paulides, M. M.

    2016-01-01

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg-1) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients’ feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R 2  =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature

  9. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF.

    PubMed

    Adibzadeh, F; van Rhoon, G C; Verduijn, G M; Naus-Postema, N C; Paulides, M M

    2016-01-21

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg(-1)) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients' feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R (2) =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature simulations as a

  10. Acute alloxan renal toxicity in the rat initially causes degeneration of thick ascending limbs of Henle

    PubMed Central

    Terayama, Yui; Kodama, Yasushi; Matsuura, Tetsuro; Ozaki, Kiyokazu

    2016-01-01

    Alloxan (AL) is a material well-known to induce diabetes. Prior to inducing a prolonged diabetic state, AL causes acute tubulointerstitial nephritis. However, the precise primary target site and mechanism of its nephrotoxicity remain unclear. The objective of this study was to evaluate the morphological characteristics relevant to acute renal toxicity following AL administration. Rats were intravenously treated with AL. Eight hours after AL treatment, aquaporin 1-negative and Na/K pump-positive thick ascending limbs of Henle (TAL) were degenerated in the outer medulla. These tubular lesions progressed from the outer medulla to the cortex. At day 2 after AL treatment, the lesions reached a peak, then both proximal and distal tubules also showed degeneration and necrosis, and tubular regeneration was seen in TAL. Immunohistochemically, damaged tubular epithelium included slightly enlarged prohibitin-positive granules, but it expressed no GLUT2, which is an AL transporter. Ultrastructurally, cytoplasmic and mitochondrial swelling was detected in degenerated cells of TAL. These findings suggest that AL initially causes degeneration of TAL, and induces mitochondrial and cellular damage in the tubular epithelium without involving GLUT2. PMID:28190920

  11. MRI-based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE.

    PubMed

    Rausch, M; Hiestand, P; Baumann, D; Cannet, C; Rudin, M

    2003-08-01

    Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model that in several respects mimics human multiple sclerosis (MS), and can be used to design or validate new strategies for treatment of this disease. In the present study, different MRI techniques (macrophage tracking based on labeling cells in vivo by ultrasmall particles of iron oxide (USPIO), blood-brain barrier (BBB) breakdown, and magnetization transfer imaging (MTI)), as well as immunohistological staining were used to study the burden of disease in Lewis rats immunized by guinea pig myelin. The resulting imaging data was compared with behavioral readouts. Animals were studied during the acute phase and the first relapse. Activated monocytes were detected during both episodes in the brain stem or cortex. These areas coincided in part with areas of BBB breakdown. Significant changes of the magnetization transfer ratios (MTRs) of up to 35% were observed in areas of USPIO accumulation. This suggests that infiltrating monocytes are the major source of demyelination in EAE, but monocyte infiltration and breakdown of the BBB are temporally or spatially independent inflammatory processes.

  12. Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage

    PubMed Central

    González-Ponce, Herson Antonio; Martínez-Saldaña, María Consolación; Rincón-Sánchez, Ana Rosa; Sumaya-Martínez, María Teresa; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Juárez, Fernando

    2016-01-01

    Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-l-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800 mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20 mmol/L APAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF. PMID:27782042

  13. Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage.

    PubMed

    González-Ponce, Herson Antonio; Martínez-Saldaña, María Consolación; Rincón-Sánchez, Ana Rosa; Sumaya-Martínez, María Teresa; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Juárez, Fernando

    2016-10-04

    Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20mmol/LAPAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF.

  14. Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion.

    PubMed

    Mohamed, Fahim; Buckley, Nicholas A; Jayamanne, Shaluka; Pickering, John W; Peake, Philip; Palangasinghe, Chathura; Wijerathna, Thilini; Ratnayake, Indira; Shihana, Fathima; Endre, Zoltan H

    2015-09-02

    Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning.

  15. Cannabidiol reduces brain damage and improves functional recovery after acute hypoxia-ischemia in newborn pigs.

    PubMed

    Lafuente, Hector; Alvarez, Francisco J; Pazos, M Ruth; Alvarez, Antonia; Rey-Santano, M Carmen; Mielgo, Victoria; Murgia-Esteve, Xabier; Hilario, Enrique; Martinez-Orgado, José

    2011-09-01

    Newborn piglets exposed to acute hypoxia-ischemia (HI) received i.v. cannabidiol (HI + CBD) or vehicle (HI + VEH). In HI + VEH, 72 h post-HI brain activity as assessed by amplitude-integrated EEG (aEEG) had only recovered to 42 ± 9% of baseline, near-infrared spectroscopy (NIRS) parameters remained lower than normal, and neurobehavioral performance was abnormal (27.8 ± 2.3 points, normal 36). In the brain, there were fewer normal and more pyknotic neurons, while astrocytes were less numerous and swollen. Cerebrospinal fluid concentration of neuronal-specific enolase (NSE) and S100β protein and brain tissue percentage of TNFα(+) cells were all higher. In contrast, in HI + CBD, aEEG had recovered to 86 ± 5%, NIRS parameters increased, and the neurobehavioral score normalized (34.3 ± 1.4 points). HI induced histological changes, and NSE and S100β concentration and TNFα(+) cell increases were suppressed by CBD. In conclusion, post-HI administration of CBD protects neurons and astrocytes, leading to histological, functional, biochemical, and neurobehavioral improvements.

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

    PubMed Central

    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

  17. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    SciTech Connect

    Qu, Wei Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  18. Acute effects of superimposed electromyostimulation during cycling on myokines and markers of muscle damage

    PubMed Central

    Wahl, P.; Hein, M.; Achtzehn, S.; Bloch, W.; Mester, J.

    2015-01-01

    Objectives: The purpose of the present study was to evaluate the effects of superimposed electromyostimulation (E) during cycling on myokines and markers of muscle damage, as E might be a useful tool to induce a high local stimulus to skeletal muscle during endurance training without performing high external workloads. Methods: 13 subjects participated in three experimental trials each lasting 60 min in a randomized order. 1) Cycling (C), 2) Cycling with superimposed E (C+E) and 3) E. Interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), creatine kinase (CK) and myoglobin were determined before (pre) and 0’, 30’, 60’, 240’ and 24h after each intervention. Results: Only C+E caused significant increases in levels of CK and myoglobin. BDNF and IL-6 significantly increased after C and C+E, however increases for IL-6 were significantly higher after C+E compared to C. Conclusion: The present study showed that superimposed E during cycling might be a useful tool to induce a high local stimulus to skeletal muscle even when performing low to moderate external workloads. This effect might be due the activation of additional muscle fibers and mild eccentric work due to the concomitant activation of agonist and antagonist. However the higher load to skeletal muscle has to be taken into account. PMID:25730652

  19. Assessment of brainstem damage by the auditory brainstem response in acute severe head injury.

    PubMed Central

    Tsubokawa, T; Nishimoto, H; Yamamoto, T; Kitamura, M; Katayama, Y; Moriyasu, N

    1980-01-01

    In 64 cases suffering from severe head injury (Glasgow coma scale: less than seven- the auditory brainstem responses (FARs) recorded at the vertex, which are thought to be volumet conducted far-field potentials reflecting the sequential electrical activities of the auditory afferen) system in the brainstem, were recorded in the neurosurgical intensive care room immediately after admission. The alterations in the responses were compared with the types of primary injury, neurological signs., CT findings and outcome following treatment. Based on the results obtained, it is concluded that the FAR is a useful indicator for predicting the effects of treatment on brainstem damage in patients with severe head injury, and that it provides more reliable information about the function of the brainstem than the neurological signs or CT findings. Moreover, it also offers a diagnostic method for primary brainstem injury. Three cases or primary brainstem injury without lesions in the supratentorial region were diagnosed by means of combined CT and FAR recording. Images PMID:7441277

  20. Effects of glycerol on human skin damaged by acute sodium lauryl sulphate treatment.

    PubMed

    Atrux-Tallau, Nicolas; Romagny, Céline; Padois, Karine; Denis, Alain; Haftek, Marek; Falson, Françoise; Pirot, Fabrice; Maibach, Howard I

    2010-08-01

    Glycerol, widely used as humectant, is known to protect against irritants and to accelerate recovery of irritated skin. However, most studies were done with topical formulations (i.e. emulsions) containing glycerol in relatively high amounts, preventing drawing conclusions from direct effects. In this study, acute chemical irritations were performed on the forearm with application of a 10% sodium lauryl sulphate (SLS) aqueous solution under occlusion for 3 h. Then, glycerol aqueous solutions from 1 to 10% were applied under occlusion for 3 h. After elimination of moist excess consecutive to occlusive condition, in ambient air for 15 and 30 min, skin barrier function was investigated by dual measurement of skin hydration and transepidermal water loss (TEWL). Treatments with SLS solution under occlusion significantly increased TEWL and decreased skin hydration as assessed by capacitance measurements. The SLS irritant property was raised by the occlusion and the water barrier function as well as water content appeared impaired. Recovery with glycerol at low doses was remarkable through a mechanism that implies its hygroscopic properties and which is saturable. This precocious effect acts through skin rehydration by enhancing water-holding capacity of stratum corneum that would facilitate the late physiological repair of impaired skin barrier. Thus, glycerol appears to substitute for natural moisturizing factors that have been washed out by the detergent action of SLS, enhancing skin hydration but without restoring skin barrier function as depicted by TEWL values that remained high. Thus, irritant contact dermatitis treated with glycerol application compensate for skin dehydration, favouring physiological process to restore water barrier function of the impaired skin. Empirical use of glycerol added topical formulations onto detergent altered skin was substantiated in the present physicochemical approach.

  1. Is plasma urotensin II concentration an indicator of myocardial damage in patients with acute coronary syndrome?

    PubMed Central

    Babińska, Magdalena; Holecki, Michał; Prochaczek, Fryderyk; Owczarek, Aleksander; Kokocińska, Danuta; Więcek, Andrzej

    2012-01-01

    Introduction Urotensin II (UII) is a vasoactive peptide secreted by endothelial cells. Increased plasma UII concentration was observed in patients with heart failure, liver cirrhosis, diabetic nephropathy and renal insufficiency. In patients with myocardial infarction both increased and decreased plasma UII concentrations were demonstrated. The aim of this study was to analyze whether plasma UII concentration reflects the severity of acute coronary syndrome (ACS). Material and methods One hundred and forty-nine consecutive patients with ACS, without age limit, were enrolled in the study. In all patients plasma concentration of creatinine, creatine kinase isoenzyme MB (CK-MB), troponin C, N-terminal prohormone of brain natriuretic peptide (NT-pro BNP), and UII were assessed, and echocardiography was performed in order to assess the degree of left ventricular hypertrophy, ejection fraction (EF) and mass (LVM). Results In patients with the highest risk (TIMI 5-7) plasma UII concentration was significantly lower than in those with low risk (TIMI 1-2): 2.61±1.47 ng/ml vs. 3.60±2.20 ng/ml. Significantly lower plasma UII concentration was found in patients with increased concentration of troponin C (2.60±1.52 ng/ml vs. 3.41±2.09 ng/ml). There was a significant negative correlation between plasma UII concentration and TIMI score or concentration of troponin C, but not CK-MB. Borderline correlation between plasma UII and ejection fraction (R = 0.157; p=0.063) or NT-proBNP (R = − 0.156; p=0.058) was found. Conclusions Decreased plasma urotensin II concentration in patients with ACS could be associated with more severe injury of myocardium. PMID:22851999

  2. Mechanisms of action of DNA-damaging anticancer drugs in treatment of carcinomas: is acute apoptosis an "off-target" effect?

    PubMed

    Havelka, Aleksandra Mandic; Berndtsson, Maria; Olofsson, Maria Hägg; Shoshan, Maria C; Linder, Stig

    2007-10-01

    DNA damage induces apoptosis of cells of hematological origin. Apoptosis is also widely believed to be the major antiproliferative mechanism of DNA damaging anticancer drugs in other cell types, and a large number of laboratories have studied drug-induced acute apoptosis (within 24 hours) of carcinoma cells. It is, however, often overlooked that induction of apoptosis of carcinoma cells generally requires drug concentrations that are at least one order of magnitude higher than those required for loss of clonogenicity. This is true for different DNA damaging drugs such as cisplatin, doxorubicin and camptothecin. We here discuss apoptosis induction by DNA damaging agents using cisplatin as an example. Recent studies have shown that cisplatin induces caspase activation in enucleated cells (cytoplasts lacking a cell nucleus). Cisplatin-induced apoptosis in both cells and cytoplasts is associated with rapid induction of cellular reactive oxygen species and increases in [Ca(2+)](i). Cisplatin has also been reported to induce clustering of Fas/CD95 in the plasma membrane. Available data suggest that the primary responses to cisplatin-induced DNA damage are induction of long-term growth arrest ("premature cell senescence") and mitotic catastrophe, whereas acute apoptosis may be due to "off-target effects" not necessarily involving DNA damage.

  3. Rap1 Ameliorates Renal Tubular Injury in Diabetic Nephropathy

    PubMed Central

    Xiao, Li; Zhu, Xuejing; Yang, Shikun; Liu, Fuyou; Zhou, Zhiguang; Zhan, Ming; Xie, Ping; Zhang, Dongshan; Li, Jun; Song, Panai; Kanwar, Yashpal S.; Sun, Lin

    2014-01-01

    Rap1b ameliorates high glucose (HG)-induced mitochondrial dysfunction in tubular cells. However, its role and precise mechanism in diabetic nephropathy (DN) in vivo remain unclear. We hypothesize that Rap1 plays a protective role in tubular damage of DN by modulating primarily the mitochondria-derived oxidative stress. The role and precise mechanisms of Rap1b on mitochondrial dysfunction and of tubular cells in DN were examined in rats with streptozotocin (STZ)-induced diabetes that have Rap1b gene transfer using an ultrasound microbubble-mediated technique as well as in renal proximal epithelial tubular cell line (HK-2) exposed to HG ambiance. The results showed that Rap1b expression decreased significantly in tubules of renal biopsies from patients with DN. Overexpression of a constitutively active Rap1b G12V notably ameliorated renal tubular mitochondrial dysfunction, oxidative stress, and apoptosis in the kidneys of STZ-induced rats, which was accompanied with increased expression of transcription factor C/EBP-β and PGC-1α. Furthermore, Rap1b G12V also decreased phosphorylation of Drp-1, a key mitochondrial fission protein, while boosting the expression of genes related to mitochondrial biogenesis and antioxidants in HK-2 cells induced by HG. These effects were imitated by transfection with C/EBP-β or PGC-1α short interfering RNA. In addition, Rap1b could modulate C/EBP-β binding to the endogenous PGC-1α promoter and the interaction between PGC-1α and catalase or mitochondrial superoxide dismutase, indicating that Rap1b ameliorates tubular injury and slows the progression of DN by modulation of mitochondrial dysfunction via C/EBP-β–PGC-1α signaling. PMID:24353183

  4. Tubular collagen scaffolds with radial elasticity for hollow organ regeneration.

    PubMed

    Versteegden, Luuk R; van Kampen, Kenny A; Janke, Heinz P; Tiemessen, Dorien M; Hoogenkamp, Henk R; Hafmans, Theo G; Roozen, Edwin A; Lomme, Roger M; van Goor, Harry; Oosterwijk, Egbert; Feitz, Wout F; van Kuppevelt, Toin H; Daamen, Willeke F

    2017-04-01

    Tubular collagen scaffolds have been used for the repair of damaged hollow organs in regenerative medicine, but they generally lack the ability to reversibly expand in radial direction, a physiological characteristic seen in many native tubular organs. In this study, tubular collagen scaffolds were prepared that display a shape recovery effect and therefore exhibit radial elasticity. Scaffolds were constructed by compression of fibrillar collagen around a star-shaped mandrel, mimicking folds in a lumen, a typical characteristic of empty tubular hollow organs, such as ureter or urethra. Shape recovery effect was introduced by in situ fixation using a star-shaped mandrel, 3D-printed clamps and cytocompatible carbodiimide crosslinking. Prepared scaffolds expanded upon increase of luminal pressure and closed to the star-shaped conformation after removal of pressure. In this study, we applied this method to construct a scaffold mimicking the dynamics of human urethra. Radial expansion and closure of the scaffold could be iteratively performed for at least 1000 cycles, burst pressure being 132±22mmHg. Scaffolds were seeded with human epithelial cells and cultured in a bioreactor under dynamic conditions mimicking urination (pulse flow of 21s every 2h). Cells adhered and formed a closed luminal layer that resisted flow conditions. In conclusion, a new type of a tubular collagen scaffold has been constructed with radial elastic-like characteristics based on the shape of the scaffold, and enabling the scaffold to reversibly expand upon increase in luminal pressure. These scaffolds may be useful for regenerative medicine of tubular organs.

  5. Global sensitivity analysis of a mathematical model of acute inflammation identifies nonlinear dependence of cumulative tissue damage on host interleukin-6 responses.

    PubMed

    Mathew, Shibin; Bartels, John; Banerjee, Ipsita; Vodovotz, Yoram

    2014-10-07

    The precise inflammatory role of the cytokine interleukin (IL)-6 and its utility as a biomarker or therapeutic target have been the source of much debate, presumably due to the complex pro- and anti-inflammatory effects of this cytokine. We previously developed a nonlinear ordinary differential equation (ODE) model to explain the dynamics of endotoxin (lipopolysaccharide; LPS)-induced acute inflammation and associated whole-animal damage/dysfunction (a proxy for the health of the organism), along with the inflammatory mediators tumor necrosis factor (TNF)-α, IL-6, IL-10, and nitric oxide (NO). The model was partially calibrated using data from endotoxemic C57Bl/6 mice. Herein, we investigated the sensitivity of the area under the damage curve (AUCD) to the 51 rate parameters of the ODE model for different levels of simulated LPS challenges using a global sensitivity approach called Random Sampling High Dimensional Model Representation (RS-HDMR). We explored sufficient parametric Monte Carlo samples to generate the variance-based Sobol' global sensitivity indices, and found that inflammatory damage was highly sensitive to the parameters affecting the activity of IL-6 during the different stages of acute inflammation. The AUCIL6 showed a bimodal distribution, with the lower peak representing healthy response and the higher peak representing sustained inflammation. Damage was minimal at low AUCIL6, giving rise to a healthy response. In contrast, intermediate levels of AUCIL6 resulted in high damage, and this was due to the insufficiency of damage recovery driven by anti-inflammatory responses from IL-10 and the activation of positive feedback sustained by IL-6. At high AUCIL6, damage recovery was interestingly restored in some population of simulated animals due to the NO-mediated anti-inflammatory responses. These observations suggest that the host's health status during acute inflammation depends in a nonlinear fashion on the magnitude of the inflammatory stimulus

  6. Long-term hematopoietic stem cell damage in a murine model of the hematopoietic syndrome of the acute radiation syndrome.

    PubMed

    Chua, Hui Lin; Plett, P Artur; Sampson, Carol H; Joshi, Mandar; Tabbey, Rebeka; Katz, Barry P; MacVittie, Thomas J; Orschell, Christie M

    2012-10-01

    Residual bone marrow damage (RBMD) persists for years following exposure to radiation and is believed to be due to decreased self-renewal potential of radiation-damaged hematopoietic stem cells (HSC). Current literature has examined primarily sublethal doses of radiation and time points within a few months of exposure. In this study, the authors examined RBMD in mice surviving lethal doses of total body ionizing irradiation (TBI) in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS). Survivors were analyzed at various time points up to 19 mo post-TBI for hematopoietic function. The competitive bone marrow (BM) repopulating potential of 150 purified c-Kit+ Sca-1+ lineage- CD150+ cells (KSLCD150+) remained severely deficient throughout the study compared to KSLCD150+ cells from non-TBI age-matched controls. The minimal engraftment from these TBI HSCs is predominantly myeloid, with minimal production of lymphocytes both in vitro and in vivo. All classes of blood cells as well as BM cellularity were significantly decreased in TBI mice, especially at later time points as mice aged. Primitive BM hematopoietic cells (KSLCD150+) displayed significantly increased cell cycling in TBI mice at all time points, which may be a physiological attempt to maintain HSC numbers in the post-irradiation state. Taken together, these data suggest that the increased cycling among primitive hematopoietic cells in survivors of lethal radiation may contribute to long-term HSC exhaustion and subsequent RBMD, exacerbated by the added insult of aging at later time points.

  7. 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

  8. Responses of proximal tubular cells to injury in congenital renal disease: fight or flight.

    PubMed

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

    2014-04-01

    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 polycystic kidney and fibrosis (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 knockout 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.

  9. Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke

    PubMed Central

    2011-01-01

    Background Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption. Methods We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years) not treated with tPA within 12 hours (h) of symptoms onset (mean time, 4.7 ± 2.1 h). Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6), Intercellular adhesion molecule-1 (ICAM-1), active Matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (cFn) (determined by ELISA) and glutamate (determined by HPLC) were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity. Results The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), MMP-9 (r = -0.554) and cFn (r = -0.703) (all P < 0.0001). In the multivariate analysis, serum levels of glutamate (OR, 1.04; CI95%, 1.01-1.06, p = 0.001); IL-6 (OR, 1.4; CI95%, 1.1-1.7, p = 0.001); and cFn (OR, 1.3; CI95%, 1.1-1.6, p = 0.002) were independently associated with a decrease of neuroserpin levels <70 ng/mL at 24 h after adjusting for confounding factors. Conclusions These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke. PMID:21569344

  10. 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)

  11. METHOD OF FABRICATING TUBULAR UNITS

    DOEpatents

    Ohlinger, L.A.

    1961-06-20

    A process is described for making a fuel element comprising a tubular jacket and fuel slugs held by the jacket in longitudinally spaced relation to one another. The jacket is lengthened as a result of being drawn down to grip the fuel slugs. As an intentional incident to this operation, the fuel slugs become longitudinally spaced from one another.

  12. Flaxseed Mitigates Acute Oxidative Lung Damage in a Mouse Model of Repeated Radiation and Hyperoxia Exposure Associated with Space Exploration

    PubMed Central

    Pietrofesa, Ralph A.; Solomides, Charalambos C.; Christofidou-Solomidou, Melpo

    2015-01-01

    Background Spaceflight missions may require crewmembers to conduct extravehicular activities (EVA). Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours and be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health. We have developed a mouse model of total body radiation and hyperoxia exposure and identified acute damage of lung tissues. In the current study we evaluated the usefulness of dietary flaxseed (FS) as a countermeasure agent for such double-hit exposures. Methods We evaluated lung tissue changes 2 weeks post-initiation of exposure challenges. Mouse cohorts (n=5/group) were pre-fed diets containing either 0% FS or 10% FS for 3 weeks and exposed to: a) normoxia (Untreated); b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) 3 times per week for 2 consecutive weeks, where 8-hour hyperoxia treatments were spanned by normoxic intervals. Results At 2 weeks post challenge, while control-diet fed mice developed significant lung injury and inflammation across all challenges, FS protected lung tissues by decreasing bronchoalveolar lavage fluid (BALF) neutrophils (p<0.003) and protein levels, oxidative tissue damage, as determined by levels of malondialdehyde (MDA) (p<0.008) and nitrosative stress as determined by nitrite levels. Lung hydroxyproline levels, a measure of lung fibrosis, were significantly elevated in mice fed 0% FS (p<0.01) and exposed to hyperoxia/radiation or the combination treatment, but not in FS-fed mice. FS also decreased levels of a pro-inflammatory, pro-fibrogenic cytokine (TGF-β1) gene expression levels in lung. Conclusion Flaxseed mitigated adverse effects in lung of repeat exposures to radiation/hyperoxia. This data will provide useful information in the design of countermeasures to early

  13. 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.

  14. Lycopene treatment prevents hematological, reproductive and histopathological damage induced by acute zearalenone administration in male Swiss mice.

    PubMed

    Boeira, Silvana Peterini; Filho, Carlos Borges; Del'Fabbro, Lucian; Roman, Silvane Souza; Royes, Luiz Fernando Freire; Fighera, Michele Rechia; Jessé, Cristiano Ricardo; Oliveira, Mauro Schneider; Furian, Ana Flávia

    2014-07-01

    Zearalenone (ZEA) is a mycotoxin commonly found as a contaminant in cereals. ZEA toxicity targets mainly the reproductive system, and oxidative stress plays an etiological role in its toxic effects. Therefore, the present study aimed to investigate the effect of lycopene, a potent carotenoid antioxidant, on markers of oxidative stress in liver, kidney and testes, and on reproductive, hematological and histopathological parameters after ZEA administration. Adult Swiss albino male mice received lycopene (20mg/kg, p.o.) for ten days before a single oral administration of ZEA (40mg/kg, p.o.), and 48h thereafter tissues (liver, kidney, testes and blood) were collected for biochemical, hematological and histological analyses. Lycopene prevented ZEA-induced changes in hematological parameters (increased number of leukocytes, segmented neutrophils, sticks, eosinophils and monocytes and decreased number of red blood cells (RBC), number of lymphocytes and platelets). Moreover, lycopene prevented the reduction in the number and motility of spermatozoa and the testicular tissue damage induced by ZEA. In addition, lycopene prevented the decrease in glutathione-S-transferase activity in kidney and testes and increased glutathione-S-transferase activity per se in the liver, kidneys and testes as well as superoxide dismutase activity in the liver. In summary, lycopene was able to prevent ZEA-induced acute toxic effects in male mice, suggesting that this antioxidant carotenoid may represent a promising prophylactic strategy against ZEA toxicity.

  15. 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.

  16. Better understanding of tubular helical buckling

    SciTech Connect

    Wu, J.

    1996-09-01

    Tubular buckling is a significant problem within the oil industry. Although it has been studied for many years, methods to analyze tubular helical buckling continues to appear in the literature. Several criteria have been derived and presented leading to confusion in understanding and correctly predicting tubular helical buckling. The prediction of tubular helical buckling is complicated by the fact that the tubular is confined within the wellbore. The tubular initially buckles sinusoidally, and then changes into the shape of a helix (helical buckling) as the axial load increases. Different approaches in modeling the helical buckling process and the use of energy methods resulted in those different helical buckling criteria. Helical buckling criteria proposed in the literature, as well as their derivations are discussed in this paper, to help better understand and effectively predict tubular helical buckling in engineering operations.

  17. Damage to pancreatic acinar cells and preservation of islets of Langerhans in a rat model of acute pancreatitis induced by Karwinskia humboldtiana (buckthorn).

    PubMed

    Carcano-Diaz, Katya; Garcia-Garcia, Aracely; Segoviano-Ramirez, Juan Carlos; Rodriguez-Rocha, Humberto; Loera-Arias, Maria de Jesus; Garcia-Juarez, Jaime

    2016-09-01

    Karwinskia humboldtiana (Kh) is a poisonous plant that grows in some regions of the American continent. Consuming large amounts of Kh fruit results in acute intoxication leading to respiratory failure, culminating in death within days. There is evidence of histological damage to the lungs, liver, and kidneys following accidental and experimental Kh intoxication. To date, the microscopic effect of Kh consumption on the pancreas has not been described. We examined the early effects of Kh fruit on pancreatic tissue at different stages of acute intoxication in the Wistar rat. We found progressive damage confined to the exocrine pancreas, starting with a reduction in the number of zymogen granules, loss of acinar architecture, the presence of autophagy-like vesicles, apoptosis and inflammatory infiltrate. The pancreatic pathology culminated in damaged acini characterized by necrosis and edema, with a complete loss of lobular architecture. Interestingly, the morphology of the islets of Langerhans was conserved throughout our evaluations. Taken together, our results indicate the damage induced by a high dose of Kh fruit in the Wistar rat is consistent with an early acute necrotizing pancreatitis that exclusively affects the exocrine pancreas. Therefore, this system might be useful as an animal model to study the treatment of pancreatic diseases. More importantly, as the islets of Langerhans were preserved, the active compounds of Kh fruit could be utilized for the treatment of acinar pancreatic cancer. Further studies might provide insight into the severity of acute Kh intoxication in humans and influence the design of treatments for pancreatic diseases and acinar pancreatic cancer.

  18. 17β-Estradiol protects against acetaminophen-overdose-induced acute oxidative hepatic damage and increases the survival rate in mice.

    PubMed

    Chandrasekaran, Victor Raj Mohan; Periasamy, Srinivasan; Liu, Li-Lian; Liu, Ming-Yie

    2011-01-01

    Acetaminophen overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of 17β-estradiol against acetaminophen-induced acute liver injury and mortality in mice. Male mice were given acetaminophen (p-acetamidophenol; 300 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased the levels of aspartate transaminase, alanine transaminase, myeloperoxidase, lipid peroxidation, and glutathione reductase, but it decreased superoxide dismutase, catalase, and glutathione. In addition, acetaminophen-induced mortality began 4h post-treatment, and all mice died within 9h. 17β-Estradiol (200 μg/kg; i.p.) protected against acetaminophen-induced oxidative hepatic damage by inhibiting neutrophil infiltration and stimulating the antioxidant defense system. However, 17β-estradiol did not affect acetaminophen-induced glutathione depletion or increased glutathione reductase activity. We conclude that 17β-estradiol specifically attenuates acute hepatic damage and decreases mortality in acetaminophen-overdosed male mice.

  19. The role of tubuloglomerular feedback in the pathogenesis of acute kidney injury.

    PubMed

    Singh, Prabhleen; Okusa, Mark D

    2011-01-01

    The mechanisms involved in reduction in glomerular filtration rate (GFR) in prerenal and intrarenal acute kidney injury (AKI) are not mutually exclusive and prerenal mechanisms continue to play a role in the pathogenesis of established intrarenal AKI. In nearly all forms of AKI, glomeruli are morphologically normal; therefore, the investigative efforts have focused on systemic and intrarenal mechanisms that lead to the failure of filtration at the glomerulus. There is observed and/or deductive evidence supporting the role of tubuloglomerular feedback in mediating the reduction in GFR in various forms of AKI. In prerenal AKI, the activation of various neurohormonal renal vasoconstrictors can increase the sensitivity and responsiveness of tubuloglomerular feedback. In different forms of intrarenal AKI, the varying degree of tubular injury is linked to filtration failure directly by mechanisms such as tubular obstruction or tubular backleak of solutes, or indirectly via the activation of tubuloglomerular feedback. Tubular obstruction or backleak of solutes, while readily understood, do not appear to be consistent features in experimental AKI and have a limited role in explaining the degree of impairment of GFR in human AKI. The functional connection between tubular damage and filtration failure mediated by tubuloglomerular feedback via alterations in nephron plasma flow and glomerular capillary hydrostatic pressure is more consistently observed or deduced from experimental data. It also explains the principal abnormality of increased preglomerular resistances, a pathogenic characteristic of both experimental and human AKI.

  20. Oxidative DNA damage after acute exposure to arsenite and monomethylarsonous acid in biomethylation-deficient human cells.

    PubMed

    Orihuela, Ruben; Kojima, Chikara; Tokar, Erik J; Person, Rachel J; Xu, Yuanyuan; Qu, Wei; Waalkes, Michael P

    2013-07-01

    The carcinogen inorganic arsenic (iAs) undergoes biomethylation (BMT) in some cells. The methylated metabolite, monomethylarsonous (MMA(3+)), may cause oxidative DNA damage (ODD). With chronic iAs exposure, BMT-competent cells show ODD while BMT-deficient do not. To further define these events, we studied ODD produced by acute iAs or MMA(3+) in the BMT-deficient human prostate cell line, RWPE-1. ODD, measured by the immuno-spin trapping method, was assessed after exposure to iAs or MMA(3+) alone, with the arsenic BMT inhibitor selenite or after glutathione (GSH) depletion. The expression of oxidative stress-related genes (HO-1, SOD-1, SOD-2, Nrf2 and Keap-1) was also assessed. Exposure to iAs at 24 h (0-20 µM), stimulated ODD only at levels above the LC50 of a 48 h exposure (17 µM). If iAs induced ODD, it also activated oxidative stress-related genes. Selenium did not alter iAs-induced ODD. MMA(3+) at 24 h (0-0.5 µM) caused ODD at levels below the LC50 of a 48 h exposure (1.5 µM), which were greatly increased by GSH depletion but not selenite. MMA(3+) induced ODD at levels not activating oxidant stress response genes. Overall, iAs induced ODD in BMT-deficient cells only at toxic levels. MMA(3+) caused ODD at non-toxic levels, independently of cellular BMT capacity and in a fashion not requiring further BMT.

  1. Sex Differences in Renal Proximal Tubular Cell Homeostasis.

    PubMed

    Seppi, Thomas; Prajczer, Sinikka; Dörler, Maria-Magdalena; Eiter, Oliver; Hekl, Daniel; Nevinny-Stickel, Meinhard; Skvortsova, Iraida; Gstraunthaler, Gerhard; Lukas, Peter; Lechner, Judith

    2016-10-01

    Studies in human patients and animals have revealed sex-specific differences in susceptibility to renal diseases. Because actions of female sex hormones on normal renal tissue might protect against damage, we searched for potential influences of the female hormone cycle on basic renal functions by studying excretion of urinary marker proteins in healthy human probands. We collected second morning spot urine samples of unmedicated naturally ovulating women, postmenopausal women, and men daily and determined urinary excretion of the renal tubular enzymes fructose-1,6-bisphosphatase and glutathione-S-transferase-α Additionally, we quantified urinary excretion of blood plasma proteins α1-microglobulin, albumin, and IgG. Naturally cycling women showed prominent peaks in the temporal pattern of urinary fructose-1,6-bisphosphatase and glutathione-S-transferase-α release exclusively within 7 days after ovulation or onset of menses. In contrast, postmenopausal women and men showed consistently low levels of urinary fructose-1,6-bisphosphatase excretion over comparable periods. We did not detect changes in urinary α1-microglobulin, albumin, or IgG excretion. Results of this study indicate that proximal tubular tissue architecture, representing a nonreproductive organ-derived epithelium, undergoes periodical adaptations phased by the female reproductive hormone cycle. The temporally delimited higher rate of enzymuria in ovulating women might be a sign of recurring increases of tubular cell turnover that potentially provide enhanced repair capacity and thus, higher resistance to renal damage.

  2. 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.

  3. Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome.

    PubMed

    Gongora, Maria Carolina; Lob, Heinrich E; Landmesser, Ulf; Guzik, Tomasz J; Martin, W David; Ozumi, Kiyoski; Wall, Susan M; Wilson, David Scott; Murthy, Niren; Gravanis, Michael; Fukai, Tohru; Harrison, David G

    2008-10-01

    The extracellular superoxide dismutase 3 (SOD3) is highly expressed in both blood vessels and lungs. In different models of pulmonary injury, SOD3 is reduced; however, it is unclear whether this contributes to lung injury. To study the role of acute SOD3 reduction in lung injury, the SOD3 gene was deleted in adult mice by using the Cre-Lox technology. Acute reduction of SOD3 led to a fivefold increase in lung superoxide, marked inflammatory cell infiltration, a threefold increase in the arterial-alveolar gradient, respiratory acidosis, histological changes similar to those observed in adult respiratory distress syndrome, and 85% mortality. Treatment with the SOD mimetic MnTBAP and intranasal administration of SOD-containing polyketal microparticles reduced mortality, prevented the histological alterations, and reduced lung superoxide levels. To understand how mice with the SOD3 embryonic deletion survived without lung injury, gene array analysis was performed. These data demonstrated the up-regulation of 37 genes and down-regulation of nine genes, including those involved in cell signaling, inflammation, and gene transcription in SOD3-/- mice compared with either mice with acute SOD3 reduction or wild-type controls. These studies show that SOD3 is essential for survival in the presence of ambient oxygen and that acute loss of this enzyme can lead to severe lung damage. Strategies either to prevent SOD3 inactivation or to augment its levels might prove useful in the treatment of acute lung injury.

  4. Effects of inorganic iron and myoglobin on in vitro proximal tubular lipid peroxidation and cytotoxicity.

    PubMed

    Zager, R A; Foerder, C A

    1992-03-01

    Recent in vivo studies suggest that heme Fe causes proximal tubular lipid peroxidation and cytotoxicity, thereby contributing to the pathogenesis of myoglobinuric (Mgb) acute renal failure. Because hydroxyl radical (.OH) scavengers [dimethylthiourea (DMTU), benzoate, mannitol] can mitigate this injury, it is postulated that .OH is a mediator of Mgb-induced renal damage. The present study has tested these hypotheses using an isolated rat proximal tubular segment (PTS) system. An equal mixture of Fe2+/Fe3+ (4 mM total), when added to PTS, caused marked cytotoxicity [as defined by lactate dehydrogenase (LDH) release] and lipid peroxidation [assessed by malondialdehyde (MDA) increments]. Fe2+ or Fe3+ alone each induced massive MDA elevations, but only Fe2+ caused cytotoxicity. Although both DMTU and benzoate decreased LDH release during the Fe2+/Fe3+ challenge, mannitol and GSH did not, despite equivalent reductions in .OH (gauged by the salicylate trap method). GSH and catalase (but not DMTU, benzoate, or mannitol) decreased MDA concentrations, suggesting the Fe-driven lipid peroxidation was more H2O2 than .OH dependent. Deferoxamine totally blocked Fe-induced LDH release, even under conditions in which it caused an apparent increase in .OH generation. Mgb paradoxically protected against Fe-mediated PTS injury, an effect largely reproduced by albumin. In conclusion, these data suggest that: (a) Fe can cause PTS lipid peroxidation and cytotoxicity by a non-.OH-dependent mechanism; (b) Fe-mediated cytotoxicity and lipid peroxidation are not necessarily linked; and (c) Mgb paradoxically protects PTS against Fe-mediated injury, suggesting that: (i) Mgb Fe may require liberation from its porphyrin ring before exerting toxicity; and (ii) the protein residue may blunt the resulting injury.

  5. Tweak induces proliferation in renal tubular epithelium: a role in uninephrectomy induced renal hyperplasia

    PubMed Central

    Sanz, Ana B; Sanchez-Niño, Maria Dolores; Izquierdo, Maria Concepcion; Jakubowski, Aniela; Justo, Pilar; Blanco-Colio, Luis M; Ruiz-Ortega, Marta; Egido, Jesús; Ortiz, Alberto

    2009-01-01

    The tumour necrosis factor (TNF) family member TWEAK activates the Fn14 receptor and has pro-apoptotic, proliferative and pro-inflammatory actions that depend on the cell type and the microenvironment. We explored the proliferative actions of TWEAK on cultured tubular cells and in vivo on renal tubules. Additionally, we studied the role of TWEAK in compensatory proliferation following unilateral nephrectomy and in an inflammatory model of acute kidney injury (AKI) induced by a folic acid overdose. TWEAK increased the proliferation, cell number and cyclin D1 expression of cultured tubular cells, in vitro. Exposure to serum increased TWEAK and Fn14 expression and the proliferative response to TWEAK. TWEAK activated the mitogen-activated protein kinases ERK and p38, the phosphatidyl-inositol 3-kinase (PI3K)/Akt pathway and NF-κB. TWEAK-induced proliferation was prevented by inhibitors of these protein kinases and by the NF-κB inhibitor parthenolide. TWEAK-induced tubular cell proliferation as assessed by PCNA and cyclin D1 expression in the kidneys of adult healthy mice in vivo. By contrast, TWEAK knock-out mice displayed lower tubular cell proliferation in the remnant kidney following unilateral nephrectomy, a non-inflammatory model. This is consistent with TWEAK-induced proliferation on cultured tubular cells in the absence of inflammatory cytokines. Consistent with our previously published data, in the presence of inflammatory cytokines TWEAK promoted apoptosis, not proliferation, of cultured tubular cells. In this regard, TWEAK knock-out mice with AKI displayed less tubular apoptosis and proliferation, as well as improved renal function. In conclusion, TWEAK actions in tubular cells are context dependent. In a non-inflammatory milieu TWEAK induces proliferation of tubular epithelium. This may be relevant for compensatory renal hyperplasia following nephrectomy. PMID:19426154

  6. Tubular aggregates: their association with myalgia.

    PubMed Central

    Niakan, E; Harati, Y; Danon, M J

    1985-01-01

    Three thousand consecutive muscle biopsies were reviewed for the presence of tubular aggregates and their association with clinical symptomatology. Tubular aggregates were detected in 19 patients (0.6%). Twelve of these nineteen patients had severe myalgia, and the most abundant tubular aggregates were found in biopsies of patients with myalgia. Seven patients had only myalgia as their clinical symptomatology with normal physical examination. An additional five patients with tubular aggregates and myalgia had concomitant amyotrophic lateral sclerosis (2) or neuropathy (3). The high incidence of myalgia associated with tubular aggregates in our patients and the fact that tubular aggregates originate from sarcoplasmic reticulum suggest a role played by this structure in the pathogenesis of myalgia. Images PMID:2995591

  7. Evaluation of the ability of bone marrow derived cells to engraft the kidney and promote renal tubular regeneration in mice following exposure to cisplatin.

    PubMed

    Bataille, Aurélien; Galichon, Pierre; Wetzstein, Morgane; Legouis, David; Vandermeersch, Sophie; Rondeau, Eric; Hertig, Alexandre

    2016-01-01

    It has been suggested that bone marrow derived stem cells have the ability to engraft the kidney and improve the outcome of severe acute kidney injury (AKI) in mice exposed to high doses of cisplatin, providing hope for cancer patients in whom irreversible renal damage occasionally occurs following the use of this highly effective anti-tumor drug. We tested the therapeutic potential of bone marrow derived cells injected during the acute phase (day 3 after cisplatin administration) of experimentally-induced AKI in C57Bl6/J mice, characterized by massive tubular necrosis, apoptosis, and a low proliferation capacity. We failed to show any benefit of bone marrow derived cells versus a regular homogenate of intact renal cells, or normal saline. Using cell tracers and flow cytometry, we demonstrated that bone marrow derived cells did indeed home to the bone marrow of the recipients but failed to settle in the kidney. Conversely, renal cells homed to injured kidneys. However, neither cell therapy protected the animals against cisplatin-induced death. We therefore question the short-term efficacy of bone marrow derived cells used to repair established injuries of the tubular epithelium.

  8. Renal tubular acidosis type 4 in pregnancy.

    PubMed

    Jakes, Adam Daniel; Baynes, Kevin; Nelson-Piercy, Catherine

    2016-03-17

    We describe the clinical course of renal tubular acidosis (RTA) type 4 in pregnancy, which has not been previously published. Renal tubular acidosis type 4 is a condition associated with increased urinary ammonia secondary to hypoaldosteronism or pseudohypoaldosteronism. Pregnancy may worsen the hyperkalaemia and acidosis of renal tubular acidosis type 4, possibly through an antialdosterone effect. We advise regular monitoring of potassium and pH throughout pregnancy to ensure safe levels are maintained.

  9. 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.

  10. Sex differences in skin carotenoid deposition and acute UVB-induced skin damage in SKH-1 hairless mice after consumption of tangerine tomatoes

    PubMed Central

    Kopec, Rachel E.; Schick, Jonathan; Tober, Kathleen L.; Riedl, Ken M.; Francis, David M.; Young, Gregory S.; Schwartz, Steven J.; Oberyszyn, Tatiana M.

    2015-01-01

    Scope UVB exposure, a major factor in the development of skin cancer, has differential sex effects. Tomato product consumption reduces the intensity of UVB-induced erythema in humans, but the mechanisms are unknown. Methods and results Four week old SKH-1 hairless mice (40 females, 40 males) were divided into two feeding groups (control or with 10% tangerine tomatoes naturally rich in UV-absorbing phytoene and phytofluene) and two UV exposure groups (with or without UV). After 10 weeks of feeding, the UV group was exposed to a single UV dose and sacrificed 48 hours later. Blood and dorsal skin samples were taken for carotenoid analysis. Dorsal skin was harvested to assess sex and UV effects on carotenoid deposition, inflammation (skinfold thickness, myeloperoxidase levels) and DNA damage (cyclobutane pyrimidine dimers, p53). Females had significantly higher levels of both skin and blood carotenoids relative to males. UV exposure significantly reduced skin carotenoid levels in females but not males. Tomato consumption attenuated acute UV-induced increases in CPD in both sexes, and reduced myeloperoxidase activity and % p53 positive epidermal cells in males. Conclusion Tangerine tomatoes mediate acute UV-induced skin damage in SKH-1 mice via reduced DNA damage in both sexes, and through reduced inflammation in males. PMID:26394800

  11. Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury.

    PubMed

    Bosmann, Markus; Grailer, Jamison J; Ruemmler, Robert; Russkamp, Norman F; Zetoune, Firas S; Sarma, J Vidya; Standiford, Theodore J; Ward, Peter A

    2013-12-01

    We investigated how complement activation promotes tissue injury and organ dysfunction during acute inflammation. Three models of acute lung injury (ALI) induced by LPS, IgG immune complexes, or C5a were used in C57BL/6 mice, all models requiring availability of both C5a receptors (C5aR and C5L2) for full development of ALI. Ligation of C5aR and C5L2 with C5a triggered the appearance of histones (H3 and H4) in bronchoalveolar lavage fluid (BALF). BALF from humans with ALI contained H4 histone. Histones were absent in control BALF from healthy volunteers. In mice with ALI, in vivo neutralization of H4 with IgG antibody reduced the intensity of ALI. Neutrophil depletion in mice with ALI markedly reduced H4 presence in BALF and was highly protective. The direct lung damaging effects of extracellular histones were demonstrated by airway administration of histones into mice and rats (Sprague-Dawley), which resulted in ALI that was C5a receptor-independent, and associated with intense inflammation, PMN accumulation, damage/destruction of alveolar epithelial cells, together with release into lung of cytokines/chemokines. High-resolution magnetic resonance imaging demonstrated lung damage, edema and consolidation in histone-injured lungs. These studies confirm the destructive C5a-dependent effects in lung linked to appearance of extracellular histones.

  12. DNA damage response in nephrotoxic and ischemic kidney injury.

    PubMed

    Yan, Mingjuan; Tang, Chengyuan; Ma, Zhengwei; Huang, Shuang; Dong, Zheng

    2016-10-27

    DNA damage activates specific cell signaling cascades for DNA repair, cell cycle arrest, senescence, and/or cell death. Recent studies have demonstrated DNA damage response (DDR) in experimental models of acute kidney injury (AKI). In cisplatin-induced AKI or nephrotoxicity, the DDR pathway of ATR/Chk2/p53 is activated and contributes to renal tubular cell apoptosis. In ischemic AKI, DDR seems more complex and involves at least the ataxia telangiectasia mutated (ATM), a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, and p53; however, while ATM may promote DNA repair, p53 may trigger cell death. Targeting DDR for kidney protection in AKI therefore relies on a thorough elucidation of the DDR pathways in various forms of AKI.

  13. Changes in Proximal and Distal Tubular Reabsorption Produced by Rapid Expansion of Extracellular Fluid*

    PubMed Central

    Hayslett, John P.; Kashgarian, Michael; Epstein, Franklin H.

    1967-01-01

    Acute infusions of isotonic saline in the rat cause an increase in glomerular filtration rate and in the excretion of salt and water. The kidney swells, due to expansion of tubular and interstitial volume. Despite the increase in tubular diameter, transit time through the proximal tubules and loops of Henle is decreased, presumably owing to a greatly accelerated rate of tubular flow. Proximal tubular reabsorption, measured in blocked tubules, is inhibited in a way that cannot be ascribed to changes in tubular diameter. The prolongation of proximal reabsorptive half-time is not affected by the administration of aldosterone. It occurs equally in rats chronically loaded with or deprived of salt, and it is therefore not likely that it is influenced by the renal content of renin. In contrast, reabsorption from the distal convoluted tubule is enhanced by saline infusion. This change is observed in segments of tubules blocked with oil and isolated from their glomeruli and thus appears to occur independently of changes in glomerular filtration or tubular flow. Images PMID:6027087

  14. Genetics Home Reference: tubular aggregate myopathy

    MedlinePlus

    ... Krahn M, Eymard B, Bartoli M, Laporte J. Constitutive activation of the calcium sensor STIM1 causes tubular- ... ORAI1 cause tubular aggregate myopathy with hypocalcemia via constitutive activation of store-operated Ca²⁺ channels. Hum Mol ...

  15. Warfarin related acute kidney injury: A case report

    PubMed Central

    Mendonca, S.; Gupta, D.; Valsan, A.; Tewari, R.

    2017-01-01

    Warfarin is an oral anticoagulant used extensively in clinical practice; However, its side-effect of causing renal damage has been recently detected. The mechanism leading to renal damage is glomerular hemorrhage and red blood cell tubular casts prothrombin time. Recently, it was found that warfarin causes renal damage in patients with chronic kidney disease and is also associated with progression of renal disease. Warfarin causing acute kidney injury in patients with normal renal function is a rare manifestation. It is important to be aware of this condition as its innocuous presence can lead to chronic kidney disease if not corrected in time. Further studies have also found that novel oral anticoagulants such as dabigatran also cause a similar syndrome and hence a new term called anticoagulant-related nephropathy is now in vogue. PMID:28182051

  16. Effects of grape seed polyphenols on oxidative damage in liver tissue of acutely and chronically exercised rats.

    PubMed

    Belviranlı, Muaz; Gökbel, Hakkı; Okudan, Nilsel; Büyükbaş, Sadık

    2013-05-01

    The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

  17. Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury

    PubMed Central

    Zhao, Wen-Yu; Zhang, Lei; Sui, Ming-Xing; Zhu, You-Hua; Zeng, Li

    2016-01-01

    Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD+ dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model. SIRT3 deletion increased the CLP-induced upregulation of the NLRP3 inflammasome and apoptosis-associated speck-like protein, resulting in the activation of oxidative stress, increased production of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and the enhancement of apoptosis, and these effects were reversed by antioxidant NAC. Our results suggest that SIRT3 plays a protective role against mitochondrial damage in the kidney by attenuating ROS production, inhibiting the NRLP3 inflammasome, attenuating oxidative stress, and downregulating IL-1β and IL-18. PMID:27620507

  18. Hyperammonaemia with distal renal tubular acidosis.

    PubMed

    Miller, S G; Schwartz, G J

    1997-11-01

    The case is reported of an infant with hyperammonaemia secondary to severe distal renal tubular acidosis. A clinical association between increased concentrations of ammonia in serum and renal tubular acidosis has not previously been described. In response to acidosis the infant's kidneys presumably increased ammonia synthesis but did not excrete ammonia, resulting in hyperammonaemia. The patient showed poor feeding, frequent vomiting, and failure to thrive, but did not have an inborn error of metabolism. This case report should alert doctors to consider renal tubular acidosis in the differential diagnosis of severely ill infants with metabolic acidosis and hyperammonaemia.

  19. The Effect of Acute Microgravity on Mechanically-Induced Membrane Damage and Membrane-Membrane Fusion Events

    NASA Technical Reports Server (NTRS)

    Clarke, Mark, S. F.; Vanderburg, Charles R.; Feedback, Daniel L.

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". This response is characterized by both membrane rupture and membrane resealing events mediated by membrane-membrane fusion. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  20. The effect of acute microgravity on mechanically-induced membrane damage and membrane-membrane fusion events

    NASA Technical Reports Server (NTRS)

    Clarke, M. S.; Vanderburg, C. R.; Feeback, D. L.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". Both membrane rupture and membrane resealing events mediated by membrane-membrane fusion characterize this response. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  1. 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

  2. The Different Effects of BMI and WC on Organ Damage in Patients from a Cardiac Rehabilitation Program after Acute Coronary Syndrome

    PubMed Central

    Xu, Lin; Zhao, Hui; Qiu, Jian; Zhu, Wei; Lei, Hongqiang; Cai, Zekun; Lin, Wan-Hua; Huang, Wenhua; Zhang, Heye; Zhang, Yuan-Ting

    2015-01-01

    One of the purposes of cardiac rehabilitation (CR) after acute coronary syndrome (ACS) is to monitor and control weight of the patient. Our study is to compare the different obesity indexes, body mass index (BMI), and waist circumference (WC), through one well-designed CR program (CRP) with ACS in Guangzhou city of Guangdong Province, China, in order to identify different effects of BMI and WC on organ damage. In our work, sixty-one patients between October 2013 and January 2014 fulfilled our study. We collected the vital signs by medical records, the clinical variables of body-metabolic status by fasting blood test, and the organ damage variables by submaximal exercise treadmill test (ETT) and ultrasonic cardiogram (UCG) both on our inpatient and four-to-five weeks of outpatient part of CRP after ACS. We mainly used two-tailed Pearson's test and liner regression to evaluate the relationship of BMI/WC and organ damage. Our results confirmed that WC could be more accurate than BMI to evaluate the cardiac function through the changes of left ventricular structure on the CRP after ACS cases. It makes sense of early diagnosis, valid evaluation, and proper adjustment to ACS in CRP of the obesity individuals in the future. PMID:26247035

  3. Acute interstitial nephritis – a reappraisal and update

    PubMed Central

    Raghavan, Rajeev; Eknoyan, Garabed

    2014-01-01

    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

  4. 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.

  5. 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.

  6. RIPK3-Mediated Necroptosis and Apoptosis Contributes to Renal Tubular Cell Progressive Loss and Chronic Kidney Disease Progression in Rats

    PubMed Central

    Zhu, Yongjun; Cui, Hongwang; Xia, Yunfeng; Gan, Hua

    2016-01-01

    Tubulointerstitial fibrosis (TIF) is caused by the progressive loss of renal tubular cells and the consequent replacement of the extracellular matrix. The progressive depletion of renal tubular cells results from apoptosis and necroptosis; however, the relative significance of each of these cell death mechanisms at different stages during the progression of chronic kidney disease (CKD) remains unclear. We sought to explore the mechanisms of renal tubular cell death during the early and intermediate stages of chronic renal damage of subtotal nephrectomied (SNx) rats. The results of tissue histological assays indicated that the numbers of necrotic dying cells and apoptotic cells were significantly higher in kidney tissues derived from a rat model of CKD. In addition, there was a significant increase in necroptosis observed by transmission electron microscopy (TEM) and an increase in the proportion of TUNEL-positive cells in kidney tissues from SNx rats compared with control rats, and necrostatin-1 (Nec-1) could inhibit necroptosis and reduce the proportion of TUNEL-positive cells. More importantly, we observed a significant increase in the incidence of necroptosis compared with apoptosis by TEM in vivo and in vitro and a significant increase in the proportion of TUNEL-positive tubular epithelial cells that did not express caspase-3 compared with those expressing cleaved caspase-3 in vitro. Furthermore, treatment with Nec-1 and zVAD strongly reduced necroptosis- and apoptosis-mediated renal tubular cell death and decreased the levels of blood urea nitrogen and serum creatinine and tubular damage scores of SNx rats. These results suggest that necroptotic cell death plays a more significant role than apoptosis in mediating the loss of renal tubular cells in SNx rats and that effectively blocking both necroptosis and apoptosis improves renal function and tubular damage at early and intermediate stages of CKD. PMID:27281190

  7. Crystal amphetamine smoking-induced acute eosinophilic pneumonia and diffuse alveolar damage: a case report and literature review.

    PubMed

    Lin, Shih-Sen; Chen, Yu-Ching; Chang, Yih-Leong; Yeh, Diana Yu-Wung; Lin, Chen-Chun

    2014-10-31

    Eosinophilic pneumonia (EP) is a disease characterized by prominent infiltration of lung structures by eosinophils. The lung interstitium is infiltrated by eosinophils, and essentially the alveolar spaces are filled with eosinophils and a fibrinous exudate, with conservation of the global architecture of the lung. Diagnosis of EP relies on pathological demonstration of alveolar eosinophilia along with characteristic clinical manifestations of nonproductive cough, dyspnea, chest pain and/or unique imaging features. EP may be categorized according to the origin: EP of undetermined origin may overlap with well-individualized syndromes, while EP with a definite cause are mainly due to infections or drug abuse. Here, we report a case of an amphetamine abuser who developed acute EP and acute respiratory distress syndrome after amphetamine inhalation. Related studies on the pathogenesis of stimulant-related lung injury and treatment strategies are also discussed.

  8. 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...

  9. Elimination of etimicin in rat kidneys and alterations of its cytotoxicity to tubular epithelial cells.

    PubMed

    Li, Z-D; Zhang, X-L; Yi, N; Zhang, F-C

    2015-05-01

    Etimicin (ETM) can accumulate in kidneys and cause tubular epithelial cell cytotoxicity. This article aims to study ETM elimination in kidneys and its nephrotoxicity, apoptosis, and histopathological insults of renal tubular epithelial cells, after repeated administration. A total of 36 rats were randomly divided into ETM-treated group and vehicle control group. Rats in ETM-treated group were treated intraperitoneally (i.p.) with 100 mg/kg/day ETM and rats in control group received physiological saline (i.p.) for 5 consecutive days. Determination of ETM concentrations accumulated in rat kidneys was carried out by high-performance liquid chromatography on the basis of derivatization with o-phthalaldehyde and by ultraviolet detector. Apoptotic renal tubular epithelial cells were identified by a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Histopathological insults in kidneys were evaluated by hematoxylin and eosin staining. On day 1 after cessation of ETM administration, the accumulation concentration was 347.50 ± 193.30 μg/g tissue; on day 15, ETM concentration became 16.71 ± 9.99 μg/g tissue. Elimination half-life of ETM in rat kidney was about 3.05 days. Apoptotic renal tubular epithelial cells induced by etimicin was recovered gradually from 1544 ± 138 n/mm(2) on day 1 to 716 ± 208 n/mm(2) on day 15. Histopathological damage was also gradually recovered from vacuolation of tubular epithelial cells as well as renal tubular edema on days 1, 3, and 7 to nearly normal on day 15. From these results, we concluded that renal tubular epithelial cell cytotoxicity induced by ETM can gradually restore with its decreasing concentration in rat kidneys.

  10. Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury.

    PubMed

    Shi, Yingfeng; Xu, Liuqing; Tang, Jinhua; Fang, Lu; Ma, Shuchen; Ma, Xiaoyan; Nie, Jing; Pi, Xiaoling; Qiu, Andong; Zhuang, Shougang; Liu, Na

    2017-03-01

    Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment.

  11. Tubular Dysfunction Mimicking Dent's Disease in 2 Infants Born with Extremely Low Birth Weight

    PubMed Central

    Awazu, Midori; Arai, Mie; Ohashi, Shoko; Takahashi, Hirotaka; Sekine, Takashi; Ikeda, Kazushige

    2017-01-01

    Two preterm infants, with extremely low birth weight born at gestational weeks 24 and 25, showed generalized proximal tubular dysfunction during their stay in the neonatal intensive care unit, including glucosuria, low molecular weight proteinuria, phosphaturia, uricosuria, enzymuria (elevated urine N-acetyl-β-D-glucosaminidase), panaminoaciduria, and hypercalciuria, associated with renal calcification. Renal tubular acidosis was not present in either patient. DNA mutation analysis for Dent's disease, performed in patient 1, was negative. Although both patients had rickets of prematurity, tubular dysfunction persisted after its resolution. Patient 2, who had severe chronic lung disease, also had elevated serum creatinine, proteinuria, and hypertension, suggesting glomerular damage. In patient 1, low molecular weight proteinuria, enzymuria, panaminoaciduria, hypercalciuria, and renal calcification were still present at the age of 8 years. In patient 2, tubular dysfunction resolved except for β2 microglobulinuria at the age of 5 years. While a reduced nephron number resulting in focal segmental glomerulosclerosis is well-known, generalized proximal tubular dysfunction can also occur in infants born preterm and/or with extremely low birth weight. PMID:28203565

  12. Chronic Neuropsychological Sequelae of Cholinesterase Inhibitors in the Absence of Structural Brain Damage: Two Cases of Acute Poisoning

    PubMed Central

    Roldán-Tapia, Lola; Leyva, Antonia; Laynez, Francisco; Santed, Fernando Sánchez

    2005-01-01

    Here we describe two cases of carbamate poisoning. Patients AMF and PVM were accidentally poisoned by cholinesterase inhibitors. The medical diagnosis in both cases was overcholinergic syndrome, as demonstrated by exposure to cholinesterase inhibitors. The widespread use of cholinesterase inhibitors, especially as pesticides, produces a great number of human poisoning events annually. The main known neurotoxic effect of these substances is cholinesterase inhibition, which causes cholinergic overstimulation. Once AMF and PVM had recovered from acute intoxication, they were subjected to extensive neuropsychological evaluation 3 and 12 months after the poisoning event. These assessments point to a cognitive deficit in attention, memory, perceptual, and motor domains 3 months after intoxication. One year later these sequelae remained, even though the brain magnetic resonance imaging (MRI) and computed tomography (CT) scans were interpreted as being within normal limits. We present these cases as examples of neuropsychological profiles of long-term sequelae related to acute poisoning by cholinesterase inhibitor pesticides and show the usefulness of neuropsychological assessment in detecting central nervous system dysfunction in the absence of biochemical or structural markers. PMID:15929901

  13. The Role of Inspiratory Muscle Training in Sickle Cell Anemia Related Pulmonary Damage due to Recurrent Acute Chest Syndrome Attacks

    PubMed Central

    Camcıoğlu, Burcu; Boşnak-Güçlü, Meral; Karadallı, Müşerrefe Nur; Akı, Şahika Zeynep; Türköz-Sucak, Gülsan

    2015-01-01

    Background. The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA) had been suffering from recurrent acute chest syndrome (ACS). Aim. To examine the effects of inspiratory muscle training (IMT) on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods. Functional exercise capacity was evaluated using six-minute walk test, respiratory muscle strength using mouth pressure device, hand grip strength using hand-held dynamometer, pain using Visual Analogue Scale, fatigue using Fatigue Severity Scale, dyspnea using Modified Medical Research Council Scale, and health related quality of life using European Organization for Research and Treatment of Cancer QOL measurement. Results. A significant improvement has been demonstrated in respiratory muscle strength, functional exercise capacity, pain, fatigue, dyspnea, and quality of life. There was no admission to emergency department due to acute chest syndrome in the following 12 months after commencing regular erythrocytapheresis. Conclusion. This is the first report demonstrating the beneficial effects of inspiratory muscle training on functional exercise capacity, respiratory muscle strength, pain, fatigue, dyspnea, and quality of life in a patient with recurrent ACS. PMID:26060589

  14. Carbon uptake in a marine diatom during acute exposure to ultraviolet B radiation: Relative importance of damage and repair

    SciTech Connect

    Lesser, M. P. ); Cullen, J.J. Dalhousie Univ., Halifax, Nova Scotia ); Neale, P.J. Univ. of California, Berkeley, CA )

    1994-04-01

    Experiments on a marine diatom, Thalassiosira pseudonana (Hustedt) clone 3H, demonstrate that under moderate photon flux densities (75 [mu]mol quanta [center dot] m[sup [minus]2][center dot]s[sup [minus]1]) of visible light inhibition of photosynthesis by supplemental ultraviolet (UV) radiation (UV-B: 280-320 nm) is well described as a hyperbolic function of UV-B irradiance for time scales of 0.5-4 h. Results are consistent with predictions of a recently developed model of photosynthesis under the influence of UV and visible irradiance. Although net destruction of chlorophyll occurs during a 4-h exposure to UV-B, and the effect is a function of exposure, the principal effect of UV-B is a decrease in chlorophyll-specific photosynthetic rate. The dependence of photoinhibition on dosage rate, rather than cumulative dose, and the hyperbolic shape of the relationship are consistent with net photoinhibition being an equilibrium between damage and repair. The ratio of damage to repair is estimated by a mathematical analysis of the inhibition of photosynthesis during exposures to UV-B. A nitrate-limited culture was much more sensitive to UV-B than were the nutrient-replete cultures, but the kinetics of photoinhibition were similar. The analysis suggests that the nutrient-limited culture was much more sensitive than the nutrient-replete cultures because repair or turnover of critical proteins associated with photosynthesis is inhibited. An inhibitor of chloroplast protein synthesis was used to suppress repair processes. Photoinhibition by UV-B was enhanced, and inhibition was a function of cumulative dose, as expected if damage were not countered by repair. The fundamental importance of repair processes should be considered in the design of field experiments and models of UV-B effects in the environment, especially in the context of vertical mixing. Repair processes must also be considered whenever biological weighting functions are developed. 69 refs., 6 figs., 3 tabs.

  15. Responsiveness of Lycopersicon pimpinellifolium to acute UV-C exposure: histo-cytochemistry of the injury and DNA damage.

    PubMed

    Iriti, M; Guarnieri, S; Faoro, F

    2007-01-01

    The in vivo and in vitro effects of UV-C (254 nm) exposure (0.039 watt . m(-2) . s for 2 h) of currant tomato (Lycopersicon pimpinellifolium), indigenous to Peru and Ecuador, were assayed. H(2)O(2) deposits, dead cells and DNA damage were localized, 12/24 h after irradiation, mainly in periveinal parenchyma of the 1st and 2nd order veins of the leaves, and before the appearance of visible symptoms, which occurred 48 h after irradiation. Cell death index was of 43.5 +/- 12% in exposed leaf tissues, 24 h after treatment. In currant tomato protoplasts, the percentage of viable cells dropped 1 h after UV-C irradiation from 97.42 +/- 2.1% to 43.38 +/- 4.2%. Afterwards, the protoplast viability progressively decreased to 40.16 +/- 7.25% at 2 h, to 38.31 +/- 6.9% at 4 h, and to 36.46 +/- 1.84% at 6 h after the exposure. The genotoxic impact of UV-C radiation on protoplasts was assessed with single cell gel electrophoresis (SCGE, or comet assay). UV-C treatment greatly enhanced DNA migration, with 75.37 +/- 3.7% of DNA in the tail versus 7.88 +/- 5.5% in the case of untreated nuclei. Oxidative stress by H(2)O(2) used as a positive control, induced a similar damage on non-irradiated protoplasts, with 71.59 +/- 5.5% of DNA in the tail, whereas oxidative stress imposed on UV-C irradiated protoplasts slightly increased the DNA damage (85.13 +/- 4.1%). According to these results, SCGE of protoplasts could be an alternative to nuclei extraction directly from leaf tissues.

  16. Exposure to sub-acute doses of fipronil and buprofezin in combination or alone induces biochemical, hematological, histopathological and genotoxic damage in common carp (Cyprinus carpio L.).

    PubMed

    Qureshi, Irfan Zia; Bibi, Asia; Shahid, Sana; Ghazanfar, Madiha

    2016-10-01

    Use of pesticides or insecticides can be highly toxic to aquatic life forms due to leaching and agricultural runoff, rains or flood. Fipronil (FP) is a GABA receptor inhibitor, while buprofezin (BPFN) is an insect growth regulator. Presently, we exposed groups of aquaria acclimated carp fish (Cyprinus carpio) for 96h to sub-lethal concentrations of fipronil (400μgL(-1); 9.15×10(-7)molL(-1)) and buprofezin (BPFN, 100mgL(-1); 1.072×10(-6)molL(-1)) singly or in combination. The extent of damage was assessed at biochemical, hematological, molecular biological and histopathological level. Results obtained in treated fish were compared statistically with those of control non-treated fish and also among treatment groups. Significance level was p<0.05. Compared to control, serum total protein and globulin concentrations decreased significantly (p<0.0001) in fish treated with FP; while albumin concentration remained unaltered with all treatments. Glucose concentration decreased significantly (p<0.002) in fish treated with FP. In contrast, combined FP+BPFN treatment and BPFN treatment caused insignificant elevation of glucose concentration. Hematological assessment demonstrated significant decrease in red blood cell and thrombocyte counts, hemoglobin concentration and hematocrit percent; while white blood cell count showed an increase in all treatment groups (p<0.0001). Blood smears from pesticide treated fish revealed aberrant erythrocyte morphologies which included necrosis, micronuclear formation and hyperchromatosis. DNA laddering assay carried out on whole blood demonstrated excessive smear formation in combined FP+BPFN and BPFN treatment groups but no smear formation was noticeable in FP treated fish. Compared to control, whole blood DNA content increased significantly in the combined FP+BPFN and BPFN treatment groups (p<0.001 and p<0.009). With all treatments histopathological changes observed in the gills were: epithelial uplifting and necrosis of lamellae

  17. Buckling and lockup of tubulars in inclined wellbores

    SciTech Connect

    Wu, J.; Juvkam-Wold, H.C.

    1994-12-31

    This paper describes sinusoidal and helical buckling of tubulars in inclined wellbores and the ``lockup`` of tubulars due to buckling. The results show that tubular buckling starts from the tubular bottom in low-inclination wellbores, where axial compressive load is largest due to tubular weight. In high inclination wellbores it may start from the top portion of the tubular, where axial compressive load is largest due to frictional drag. This clarifies the confusion about whether or not tubulars buckle all at once, in the entire inclined wellbore. New sinusoidal and helical buckling load equations are presented to give better tubular buckling prediction in inclined wellbores (0--90 degrees). They show that the lower the wellbore inclination angle, the smaller the axial compressive load to initiate tubular buckling. But a certain non-zero axial compressive load is still needed to buckle the tubulars in vertical wellbores. When tubulars buckle helically, a large wall contact force will be generated. The `slack-off` weight at the surface will not be fully transmitted to the bottom of the tubulars due to the large resultant frictional drag. The ``lockup`` of tubulars, where the bottom load (bit weight) cannot be increased by slacking-off weight at the surface, usually is approached when a large portion of the tubular buckles helically in the wellbore.

  18. Buckling and lockup of tubulars in inclined wellbores

    SciTech Connect

    Wu, J.; Juvkam-Wold, H.C.

    1995-09-01

    This paper studies sinusoidal and helical buckling of tubulars in inclined wellbores and the ``lockup`` of tubulars due to buckling. The results show that tubular buckling starts from the tubular bottom in low-inclination wellbores, where the axial compressive load is largest due to tubular weight. In high-inclination wellbores it may start from the top portion of the tubular, where the axial compressive load is largest due to frictional drag. This clarifies the confusion on whether or not the tubular buckles at once on it entire length in inclined wellbores. New sinusoidal and helical buckling load equations are presented to better predict tubular buckling in inclined wellbores (0--90 deg). The lower the wellbore inclination angle, the smaller the axial compressive load required to initiate tubular buckling. However, a certain nonzero axial compressive load is still needed to buckle the tubulars in vertical wellbores. When tubulars buckle helically, a large wall contact force will be generated, and the ``slack-off`` weight at the surface will not be fully transmitted to the tubular bottom due to large resultant frictional drag. The ``lockup`` of tubulars may even occur, where the tubular bottom load cannot be increased by slacking-off weight at the surface.

  19. Pleiotropic effects of spongean alkaloids on mechanisms of cell death, cell cycle progression and DNA damage response (DDR) of acute myeloid leukemia (AML) cells.

    PubMed

    Stuhldreier, Fabian; Kassel, Stefanie; Schumacher, Lena; Wesselborg, Sebastian; Proksch, Peter; Fritz, Gerhard

    2015-05-28

    We investigated cytotoxic mechanisms evoked by the spongean alkaloids aaptamine (Aa) and aeroplysinin-1 (Ap), applied alone and in combination with daunorubicin, employing acute myeloid leukemia (AML) cells. Aa and Ap reduced the viability of AML cells in a dose dependent manner with IC50 of 10-20 µM. Ap triggered apoptotic cell death more efficiently than Aa. Both alkaloids increased the protein level of S139-phosphorylated H2AX (γH2AX), which however was independent of the induction of DNA damage. Expression of the senescence markers p21 and p16 was increased, while the phosphorylation level of p-Chk-2 was reduced following Aa treatment. As a function of dose, Aa and Ap protected or sensitized AML cells against daunorubicin. Protection by Aa was paralleled by reduced formation of ROS and lower level of DNA damage. Both Aa and Ap attenuated daunorubicin-stimulated activation of the DNA damage response (DDR) as reflected on the levels of γH2AX, p-Kap-1 and p-Chk-1. Specifically Ap restored the decrease in S10 phosphorylation of histone H3 resulting from daunorubicin treatment. The cytoprotective effects of Aa and Ap were independent of daunorubicin import/export. Both Aa and Ap abrogated daunorubicin-induced accumulation of cells in S-phase. Inhibition of DNA synthesis was specific for Ap. The data show that Aa and Ap have both congruent and agent-specific pleiotropic effects that are preferential for anticancer drugs. Since Ap showed a broader spectrum of anticancer activities, this compound is suggested as novel lead compound for forthcoming in vivo studies elucidating the usefulness of spongean alkaloids in AML therapy.

  20. Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf

    PubMed Central

    Jothy, Subramanion L.; Chen, Yeng; Kanwar, Jagat R.; Sasidharan, Sreenivasan

    2013-01-01

    Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of  ∙OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 μg/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats. PMID:23878610

  1. Autophagy in Acute Kidney Injury

    PubMed Central

    Livingston, Man J.; Dong, Zheng

    2014-01-01

    Acute kidney injury is a major kidney disease associated with poor clinical outcomes. The pathogenesis of acute kidney injury is multifactorial and is characterized by tubular cell injury and death. Recent studies have demonstrated autophagy induction in proximal tubular cells during acute kidney injury. The regulatory mechanisms of tubular cell autophagy are poorly understood; however, some recent findings have set up a foundation for further investigation. Although autophagy may promote cell death under certain experimental conditions, pharmacological and autophagy-related gene knockout studies have established a renoprotective role for autophagy in acute kidney injury. The mechanisms by which autophagy protects cells from injury and how, possibly, its pro-survival role switches to pro-death under certain conditions are discussed. Further research is expected to help us understand the regulatory network of tubular cell autophagy, define its precise roles in specific context of acute kidney injury, and identify autophagy-targeting strategies for the prevention and treatment of acute kidney injury. PMID:24485026

  2. Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats

    PubMed Central

    King, Tristan J.; Shandala, Tetyana; Lee, Alice M.; Foster, Bruce K.; Chen, Ke-Ming; Howe, Peter R.; Xian, Cory J.

    2015-01-01

    Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage. PMID:26258775

  3. Anterior ST segment depression in acute inferior myocardial infarction as a marker of greater inferior, apical, and posterolateral damage

    SciTech Connect

    Ruddy, T.D.; Yasuda, T.; Gold, H.K.; Leinbach, R.C.; Newell, J.B.; McKusick, K.A.; Boucher, C.A.; Strauss, H.W.

    1986-12-01

    The clinical significance of anterior precordial ST segment depression during acute inferior myocardial infarction was evaluated in 67 consecutive patients early after onset of symptoms with gated blood pool scans, thallium-201 perfusion images, and 12-lead ECGs. Patients with anterior ST depression (n = 33) had depressed mean values for left ventricular ejection fraction (54 +/- 2% (mean +/- S.E.M.) vs 59 +/- 2%; p = 0.02), cardiac index (3.1 +/- 0.2 vs 3.6 +/- 0.2 L/m2; p = 0.03), and ratio of systolic blood pressure to end-systolic volume (2.0 +/- 0.1 vs 2.5 +/- 0.3 mm Hg/ml; p = 0.04) compared to patients with no anterior ST depression (n = 34). Patients with anterior ST depression had (1) lower mean wall motion values for the inferior, apical, and inferior posterolateral segments (p less than 0.05) and (2) greater reductions in thallium-201 uptake in the inferior and posterolateral regions (p less than 0.05). However, anterior and septal (1) wall motion and (2) thallium-201 uptake were similar in patients with and without ST depression. Thus, anterior precordial ST segment depression in patients with acute inferior wall myocardial infarction represents more than a reciprocal electrical phenomenon. It identifies patients with more severe wall motion impairment and greater hypoperfusion of the inferior and adjacent segments. The poorer global left ventricular function in these patients is a result of more extensive inferior infarction and not of remote septal or anterior injury.

  4. 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.

  5. Downregulation of miR-205 Modulates Cell Susceptibility to Oxidative and Endoplasmic Reticulum Stresses in Renal Tubular Cells

    PubMed Central

    Muratsu-Ikeda, Shiyo; Nangaku, Masaomi; Ikeda, Yoichiro; Tanaka, Tetsuhiro; Wada, Takehiko; Inagi, Reiko

    2012-01-01

    Background Oxidative stress and endoplasmic reticulum (ER) stress play a crucial role in tubular damage in both acute kidney injury (AKI) and chronic kidney disease (CKD). While the pathophysiological contribution of microRNAs (miRNA) to renal damage has also been highlighted, the effect of miRNA on renal damage under oxidative and ER stresses conditions remains elusive. Methods We assessed changes in miRNA expression in the cultured renal tubular cell line HK-2 under hypoxia-reoxygenation-induced oxidative stress or ER stress using miRNA microarray assay and real-time RT-PCR. The pathophysiological effect of miRNA was evaluated by cell survival rate, intracellular reactive oxygen species (ROS) level, and anti-oxidant enzyme expression in miRNA-inhibited HK-2 or miRNA-overexpressed HK-2 under these stress conditions. The target gene of miRNA was identified by 3′-UTR-luciferase assay. Results We identified 8 and 10 miRNAs whose expression was significantly altered by oxidative and ER stresses, respectively. Among these, expression of miR-205 was markedly decreased in both stress conditions. Functional analysis revealed that decreased miR-205 led to an increase in cell susceptibility to oxidative and ER stresses, and that this increase was associated with the induction of intracellular ROS and suppression of anti-oxidant enzymes. While increased miR-205 by itself made no change in cell growth or morphology, cell viability under oxidative or ER stress conditions was partially restored. Further, miR-205 bound to the 3′-UTR of the prolyl hydroxylase 1 (PHD1/EGLN2) gene and suppressed the transcription level of EGLN2, which modulates both intracellular ROS level and ER stress state. Conclusions miR-205 serves a protective role against both oxidative and ER stresses via the suppression of EGLN2 and subsequent decrease in intracellular ROS. miR-205 may represent a novel therapeutic target in AKI and CKD associated with oxidative or ER stress in tubules. PMID:22859986

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Acute kidney failure

    MedlinePlus

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  11. An experimental investigation of fatigue crack growth in drillstring tubulars

    SciTech Connect

    Dale, B.A.

    1986-01-01

    Drill-string failures continue to plague the oil industry, often costing millions of dollars each year. This problem is frequently intensified with the drilling of deep deviated wellbores or ''hard rock'' drilling conditions. The drilling industry attempts to guard against these costly failures by performing periodic nondestructive inspections to remove damaged tubulars from service. This paper describes the results of full-scale fatigue crack growth tests of drill collars under rotating and bending loads. In addition, corrosion fatigue crack growth data are also presented for API drill-pipe steels in air and in three representative water-base drilling fluid environments. Based on this experimental investigation, the test data support the practical application of fatigue crack growth mechanics principles for the development of nondestructive inspection intervals to reduce drill-string failures.

  12. The effect of wellbore curvature on tubular buckling and lockup

    SciTech Connect

    Wu, J.; Juvkam-Wold, H.C.

    1995-09-01

    This paper studies tubular buckling in curved wellbores (such as the build section of horizontal wells) and its effect on tubular ``lockup`` in horizontal or extended-reach wells. New buckling load equations are derived to properly predict tubular sinusoidal and helical buckling in such wellbores. The results show that the buckling loads to initiate sinusoidal and helical buckling to tubulars in curved wellbores are usually much larger than those in straight wellbores. This is because the curved wellbore tends to hold the axially compressed tubular against the outer-curve side of the wellbore. The tubular becomes less easy to buckle until higher axial compressive loads are applied. Less tubular lockup risk is then predicted for tubulars in horizontal or extended-reach wells by using the new buckling load equations. The new buckling loads in curved wellbores agree with those in straight wellbores when wellbore curvature approaches zero. Small-scale laboratory experiments also confirmed these theoretically derived buckling loads.

  13. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells.

    PubMed

    Scuto, Anna; Kirschbaum, Mark; Kowolik, Claudia; Kretzner, Leo; Juhasz, Agnes; Atadja, Peter; Pullarkat, Vinod; Bhatia, Ravi; Forman, Stephen; Yen, Yun; Jove, Richard

    2008-05-15

    We investigated the mechanism of action of LBH589, a novel broad-spectrum HDAC inhibitor belonging to the hydroxamate class, in Philadelphia chromosome-negative (Ph(-)) acute lymphoblastic leukemia (ALL). Two model human Ph(-) ALL cell lines (T-cell MOLT-4 and pre-B-cell Reh) were treated with LBH589 and evaluated for biologic and gene expression responses. Low nanomolar concentrations (IC(50): 5-20 nM) of LBH589 induced cell-cycle arrest, apoptosis, and histone (H3K9 and H4K8) hyperacetylation. LBH589 treatment increased mRNA levels of proapoptosis, growth arrest, and DNA damage repair genes including FANCG, FOXO3A, GADD45A, GADD45B, and GADD45G. The most dramatically expressed gene (up to 45-fold induction) observed after treatment with LBH589 is GADD45G. LBH589 treatment was associated with increased histone acetylation at the GADD45G promoter and phosphorylation of histone H2A.X. Furthermore, treatment with LBH589 was active against cultured primary Ph(-) ALL cells, including those from a relapsed patient, inducing loss of cell viability (up to 70%) and induction of GADD45G mRNA expression (up to 35-fold). Thus, LBH589 possesses potent growth inhibitory activity against including Ph(-) ALL cells associated with up-regulation of genes critical for DNA damage response and growth arrest. These findings provide a rationale for exploring the clinical activity of LBH589 in the treatment of patients with Ph(-) ALL.

  14. Boron--epoxy tubular structure members

    NASA Technical Reports Server (NTRS)

    Shakespeare, W. B. J.; Nelson, P. T.; Lindkvist, E. C.

    1973-01-01

    Composite materials fabricate thin-walled tubular members which have same load-carrying capabilities as aluminum, titanium, or other metals, but are lighter. Interface between stepped end fitting and tube lends itself to attachments by primary as well as secondary bonding. Interlaminar shear and hoop stress buildup in attachment at end fitting is avoided.

  15. Comparative physiology of renal tubular transport mechanisms.

    PubMed Central

    Long, S.; Giebisch, G.

    1979-01-01

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

  16. 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.

  17. 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.

  18. 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

  19. Combined hot-spot stress procedures for tubular joints

    SciTech Connect

    Buitrayo, J.; Kahlich, J.L.; Zettlemoyer, N.

    1984-05-01

    An alternative procedure for predicting the combined hot-spot stress (CHSS) at tubular K and Y joints under combined branch loading is presented. The procedure makes use of influence factor (IF) equations developed, as a function of the joint geometry and branch loading, for various potential hot-spot locations on the branch and chord sides of the weld. The CHSS is obtained by lineraly superimposing, at a point, the effects of the axial force and bending moments acting on each branch. The resulting CHSS, therefore, reflects location, orientation and sign of each branch load contribution. Comparisons of predicted CHSS obtained via the new and other procedures to stresses from finite element analyses were made on a large sample of joints. Result show that (1) the new procedure is substantially more reliable than the other procedures studied, (2) none of the procedures consistently predicts conservative CHSS values, and (3) the overriding factor influencing the accuracy of the CHSS calculations appears to be the accuracy of the parametric equations. Although a better stress predictor can be expected to yield more reliable fatigue damage estimates, damage calculations will exhibit broad scatter due to the power function relating damage to stress. Unfortunately, further improvements in the accuracy of CHSS based on parametric equations are not likely to be easily achieved, given the large number of variables and locations that need to be considered.

  20. Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients

    PubMed Central

    Büscher, Rainer; Grosse-Onnebrink, Jörg; Hoyer, Peter F.; Mellies, Uwe

    2017-01-01

    Introduction. Antibiotic treatment regimens against Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients often include aminoglycoside antibiotics that may cause chronic renal failure after repeated courses. Aminoaciduria is an early marker of acute aminoglycoside-induced renal tubular dysfunction. We hypothesized that urinary amino acid reabsorption is decreased after repeated once-daily tobramycin therapies. Methods. In this prospective cross-sectional study creatinine clearance was estimated by the Schwartz and the Cockcroft-Gault formula. Tubular amino acid reabsorption was determined by ion exchange chromatography in 46 patients with CF who received multiple tobramycin courses (6.3 ± 10.1 (1–57)) in a once-daily dosing regimen and 10 who did not. Results. Estimated creatinine clearance employing the Cockcroft-Gault was mildly reduced in 17/46 (37%) of the patients who received tobramycin and 5/10 (50%) of the patients who did not but in none using the Schwartz formula. No association with lifetime tobramycin courses was found. Tubular amino acid reabsorption was not influenced by the amount of once-daily tobramycin courses. Conclusion. Clinically not significant reduction of eCCL occurred in a minority of CF patients. However, chronic tubular dysfunction was not present in patients with CF repeatedly treated with tobramycin in the once-daily dosing scheme. PMID:28133546

  1. Mitogenic action of lysophosphatidic acid in proximal tubular epithelial cells obtained from voided human urine.

    PubMed

    Kumagai, N; Inoue, C N; Kondo, Y; Iinuma, K

    2000-12-01

    Focal tubular cell multiplication at sites on an injured nephron is a critical event in the recovery phase following acute tubular necrosis. During this process, numerous viable tubular cells exfoliate and are shed into the urine. Lysophosphatidic acid (LPA) is generated in the plasma membrane of injured cells and acts as an intercellular mediator of various biological processes, including inflammation, proliferation and repair. In the present study, exfoliated proximal tubule (PT) cells were isolated from human urine and the mitogenic effects of LPA were investigated as a model of repair and proliferation following renal injury. LPA stimulated a 23. 5% increase in DNA synthesis, a 29.4% increase in cell number and an 86.6% decrease in cAMP content. All of these responses were pertussis toxin sensitive, indicating the involvement of G(i)-type G-proteins in LPA signalling. Conversely, the LPA-induced DNA synthesis and the decrease in intracellular cAMP content were insensitive to wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), suggesting a mitogenic response via PI3K-independent mechanisms. Furthermore, we detected specific mRNA transcripts for the recently cloned human LPA-receptors, endothelial differentiation gene (Edg)-2 and Edg-4 (Edg-2>Edg-4) by reverse transcription-PCR in PT cells. Our data suggest that LPA may behave as a local growth factor in PT cells following tubular injury.

  2. Tissue Kim-1 and urinary clusterin as early indicators of cisplatin-induced acute kidney injury in rats.

    PubMed

    Vinken, Petra; Starckx, Sofie; Barale-Thomas, Erio; Looszova, Adriana; Sonee, Manisha; Goeminne, Nick; Versmissen, Loes; Buyens, Kristel; Lampo, Ann

    2012-10-01

    The kidney is one of the main targets of drug toxicity, and early detection of renal damage is critical in preclinical drug development. A model of cisplatin-induced nephrotoxicity in male Sprague Dawley rats treated for 1, 3, 5, 7, or 14 days at 1 mg/kg/day was used to monitor the spatial and temporal expression of various indicators of kidney toxicity during the progression of acute kidney injury (AKI). As early as 1 day after cisplatin treatment, positive kidney injury molecule-1 (Kim-1) immunostaining, observed in the outer medulla of the kidney, and changes in urinary clusterin indicated the onset of proximal tubular injury in the absence of functional effects. After 3 days of treatment, Kim-1 protein levels in urine increased more than 20-fold concomitant with a positive clusterin immunostaining and an increase in urinary osteopontin. Tubular basophilia was also noted, while serum creatinine and blood urea nitrogen levels were elevated only after 5 days, together with tubular degeneration. In conclusion, tissue Kim-1 and urinary clusterin were the most sensitive biomarkers for detection of cisplatin-induced kidney damage. Thereafter, urinary Kim-1 and osteopontin, as well as clusterin immunostaining accurately correlated with the histopathological findings. When AKI is suspected in preclinical rat studies, Kim-1, clusterin, and osteopontin should be part of urinalysis and/or IHC can be performed.

  3. 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...

  4. Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation

    SciTech Connect

    Matsui, Takanori; Yamagishi, Sho-ichi; Takeuchi, Masayoshi; Ueda, Seiji; Fukami, Kei; Okuda, Seiya

    2010-07-23

    Research highlights: {yields} Nifedipine inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma}. {yields} GW9662 treatment alone increased RAGE mRNA levels in tubular cells. {yields} Nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-{kappa}B activation and increases in intercellular adhesion molecule-1 and transforming growth factor-{beta} gene expression in tubular cells, all of which were blocked by GW9662. -- Abstract: There is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) interaction evokes oxidative stress generation and subsequently elicits inflammatory and fibrogenic reactions, thereby contributing to the development and progression of diabetic nephropathy. We have previously found that nifedipine, a calcium-channel blocker (CCB), inhibits the AGE-induced mesangial cell damage in vitro. However, effects of nifedipine on proximal tubular cell injury remain unknown. We examined here whether and how nifedipine blocked the AGE-induced tubular cell damage. Nifedipine, but not amlodipine, a control CCB, inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}). GW9662 treatment alone was found to increase RAGE mRNA levels in tubular cells. Further, nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-{kappa}B activation and increases in intercellular adhesion molecule-1 and transforming growth factor-beta gene expression in tubular cells, all of which were blocked by GW9662. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-oxidative and anti-inflammatory agent against AGEs in tubular cells by suppressing RAGE expression

  5. Optical analysis of solar energy tubular absorbers.

    PubMed

    Saltiel, C; Sokolov, M

    1982-11-15

    The energy absorbed by a solar energy tubular receiver element for a single incident ray is derived. Two types of receiver elements were analyzed: (1) an inner tube with an absorbing coating surrounded by a semitransparent cover tube, and (2) a semitransparent inner tube filled with an absorbing fluid surrounded by a semitransparent cover tube. The formation of ray cascades in the semitransparent tubes is considered. A numerical simulation to investigate the influence of the angle of incidence, sizing, thickness, and coefficient of extinction of the tubes was performed. A comparison was made between receiver elements with and without cover tubes. Ray tracing analyses in which rays were followed within the tubular receiver element as well as throughout the rest of the collector were performed for parabolic and circular trough concentrating collectors.

  6. 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.

  7. 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.

  8. 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.

  9. Study of hydrodynamic characteristics in tubular photobioreactors.

    PubMed

    Zhang, Qinghua; Wu, Xia; Xue, Shengzhang; Liang, Kehong; Cong, Wei

    2013-02-01

    In this work, the hydrodynamic characteristics in tubular photobioreactors with a series of helical static mixers built-in were numerically investigated using computational fluid dynamics (CFD). The influences of height and screw pitch of the helical static mixer and fluid inlet velocity on the cell trajectories, swirl numbers and energy consumption were examined. In order to verify the actual results for cultivation of microalgae, cultivation experiments of freshwater Chlorella sp. were carried out in photobioreactor with and without helical static mixer built-in at the same time. It was shown that with built-in helical static mixer, the mixing of fluid could be intensified, and the light/dark cycle could also be achieved which is of benefit for the growth of microalgae. The biomass productivity of Chlorella sp. in tubular photobioreactor with helical static mixer built-in was 37.26 % higher than that in the photobioreactor without helical static mixer.

  10. Tubular solid oxide fuel cell developments

    NASA Astrophysics Data System (ADS)

    Bratton, R. J.; Singh, P.

    An overview of the tubular solid oxide fuel cell (SOFC) development at Westinghouse is presented in this paper. The basic operating principles of SOFC's, evolution in tubular cell design and performance improvement, selection criteria for cell component materials, and cell processing techniques are discussed. The commercial goal is to develop a cell that can operate for 5 to 10 years. Results of cell test operated for more than 50,000 hours are presented. Since 1986, significant progress has been made in the evolution of cells with higher power, lower cost and improved thermal cyclic capability. Also in this period, successively larger multi-kilowatt electrical generators systems have been built and successfully operated for more than 7000 hours.

  11. 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)

  12. 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.

  13. Mechanisms in hyperkalemic renal tubular acidosis.

    PubMed

    Karet, Fiona E

    2009-02-01

    The form of renal tubular acidosis associated with hyperkalemia is usually attributable to real or apparent hypoaldosteronism. It is therefore a common feature in diabetes and a number of other conditions associated with underproduction of renin or aldosterone. In addition, the close relationship between potassium levels and ammonia production dictates that hyperkalemia per se can lead to acidosis. Here I describe the modern relationship between molecular function of the distal portion of the nephron, pathways of ammoniagenesis, and hyperkalemia.

  14. Distal renal tubular acidosis with hereditary spherocytosis.

    PubMed

    Sinha, Rajiv; Agarwal, Indira; Bawazir, Waleed M; Bruce, Lesley J

    2013-07-01

    Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with co-existence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.

  15. Stress concentration factors for dented tubular members

    SciTech Connect

    Buitrago, J.; Hsu, T.M.

    1996-12-31

    This paper presents results of a finite element (FE) study conducted on /tubular members with dents of various geometries, including dents with circular and elliptical cross-sectional shapes. The modeling and analysis procedures are discussed, and stress concentration factors (SCFs) are generated for axial and bending loads in the member. Equations that give SCFs as function of the member size and dent geometry are developed for both load conditions. Then, simplified equations are proposed for structural assessment purposes.

  16. 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.

  17. Disruption of Renal Tubular Mitochondrial Quality Control by Myo-Inositol Oxygenase in Diabetic Kidney Disease

    PubMed Central

    Zhan, Ming; Usman, Irtaza M.; Sun, Lin

    2015-01-01

    Diabetic kidney disease (DKD) is associated with oxidative stress and mitochondrial injury. Myo-inositol oxygenase (MIOX), a tubular-specific enzyme, modulates redox imbalance and apoptosis in tubular cells in diabetes, but these mechanisms remain unclear. We investigated the role of MIOX in perturbation of mitochondrial quality control, including mitochondrial dynamics and autophagy/mitophagy, under high-glucose (HG) ambience or a diabetic state. HK-2 or LLC-PK1 cells subjected to HG exhibited an upregulation of MIOX accompanied by mitochondrial fragmentation and depolarization, inhibition of autophagy/mitophagy, and altered expression of mitochondrial dynamic and mitophagic proteins. Furthermore, dysfunctional mitochondria accumulated in the cytoplasm, which coincided with increased reactive oxygen species generation, Bax activation, cytochrome C release, and apoptosis. Overexpression of MIOX in LLC-PK1 cells enhanced the effects of HG, whereas MIOX siRNA or d-glucarate, an inhibitor of MIOX, partially reversed these perturbations. Moreover, decreasing the expression of MIOX under HG ambience increased PTEN-induced putative kinase 1 expression and the dependent mitofusin-2–Parkin interaction. In tubules of diabetic mice, increased MIOX expression and mitochondrial fragmentation and defective autophagy were observed. Dietary supplementation of d-glucarate in diabetic mice decreased MIOX expression, attenuated tubular damage, and improved renal functions. Notably, d-glucarate administration also partially attenuated mitochondrial fragmentation, oxidative stress, and apoptosis and restored autophagy/mitophagy in the tubular cells of these mice. These results suggest a novel mechanism linking MIOX to impaired mitochondrial quality control during tubular injury in the pathogenesis of DKD and suggest d-glucarate as a potential therapeutic agent for the amelioration of DKD. PMID:25270067

  18. Behavior of horizontally curved steel tubular-flange bridge girders

    NASA Astrophysics Data System (ADS)

    Fan, Zhuo

    A new type of curved steel bridge girder, called a curved tubular-flange girder, with rectangular tubes as flanges, is proposed and studied in this dissertation. A curved steel tubular-flange girder has much larger torsional stiffness than a curved I-girder and less potential for cross section distortion than a curved box-girder. Therefore, it has potential advantages compared to curved I-girders and box-girders. A theoretical analysis method for systems of curved tubular-flange girders braced by cross frames is presented. A stress analysis method for tubular-flange girders is also provided. The behavior of curved tubular-flange girder systems is studied using the theoretical analysis method and compared to the behavior of the corresponding curved I-girder systems. A parametric study is performed using the theoretical analysis method to investigate the effects of geometric parameters on the behavior of curved tubular-flange girder systems. The studied parameters include tubular-flange width, tubular-flange depth, cross section depth, girder curvature, and the number of cross frames. Finite element analyses are conducted to verify the theoretical analysis method, to study the behavior of a curved tubular-flange girder system under dead load, and to study the behavior of a curved tubular-flange girder system with a composite concrete deck under dead and live load. The study shows that a curved tubular-flange girder system develops much less warping normal stress and cross section rotation than a corresponding curved I-girder system. The difference is especially significant for a single curved girder under its own weight, suggesting that curved tubular-flange girders would be much easier to transport and erect than curved I-girders. As girder curvature increases, the rate of increase in the stresses and displacements for a single I-girder is much greater than for a single curved tubular-flange girder. Smaller cross frame forces develop in a tubular-flange girder

  19. 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.

  20. Renal tubular acidosis: an immunopathological study on four patients

    PubMed Central

    Pasternack, A.; Linder, E.

    1970-01-01

    Renal biopsies and sera of four patients with distal renal tubular acidosis were examined. The findings consisted of immunoglobulin containing mononuclear cellular infiltrates around the distal tubules, bound immunoglobulin and complement in tubules. The sera of the patients contained antibodies reacting with various tissue antigens, among them renal tubular antigens. The results suggest that autoimmunity was involved in the pathogenesis of the renal tubular acidosis in these patients. ImagesFig. 1Fig. 2 PMID:5202740

  1. 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).

  2. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression.

    PubMed

    Ishibashi, Y; Matsui, T; Takeuchi, M; Yamagishi, S

    2012-11-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in tubulointerstitial damage in diabetic nephropathy. Recently, metformin has been shown to ameliorate tubular injury both in cell culture and diabetic animal model. However, effects of metformin on AGEs-induced tubular cell apoptosis and damage remain unknown. We examined here whether and how metformin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was evaluated by DNA fragmentation and annexin V expression level. AGEs upregulated RAGE mRNA levels and subsequently increased ROS generation and intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and transforming growth factor-β gene expression in human renal proximal tubular cells, all of which were significantly blocked by the treatment of 0.01 and 0.1 mM metformin. Compound C, an inhibitor of AMP-activated protein kinase significantly blocked the effects of metformin on RAGE gene expression and ROS generation in AGEs-exposed tubular cells. Furthermore, metformin dose-dependently inhibited the AGEs-induced apoptotic cell death of tubular cells; 1 mM metformin completely suppressed the pro-apoptotic effects of AGEs in 2 different assay systems. Our present study suggests that metformin could inhibit the AGEs-induced apoptosis and inflammatory and fibrotic reactions in tubular cells probably by reducing ROS generation via suppression of RAGE expression through AMP-activated protein kinase activation. Metformin may protect against tubular cell injury in diabetic nephropathy by blocking the AGEs-RAGE-ROS axis.

  3. Renal tubular acidosis in chronic liver disease

    PubMed Central

    Golding, Peter L.

    1975-01-01

    Renal tubular acidosis of the gradient or classic type, thought to be due to a disorder of the distal tubule, has been found to occur in 32% of 117 patients with chronic liver disease. Whilst the cause of this disorder is probably multifactorial, immunological mechanisms are considered to play a major role. The presence of this disorder might well be a cause, rather than the result of, the various electrolyte abnormalities seen in patients with chronic liver disease. ImagesFig. 1Fig. 6 PMID:1234340

  4. 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.

  5. Connection pad design for underwater tubular structures

    SciTech Connect

    Tsai, C.L.; Feng, Z.; Grantham, J.A. . Dept. of Welding Engineering); Soisson, L. )

    1990-01-01

    This paper reports on research to optimize the connection pad assembly design for different types of loading conditions, which means minimizing the stresses in the wet welds and maximizing the energy absorption of the connection pad. The tubular geometry of the connection pad does not allow stress field analysis by the traditional strength-of-materials method. The authors discuss how, using the finite element method to analyze the stress contributions and the energy absorbed by the pad, the optimum pad dimensions could be determined for different types of loads.

  6. Intraductal tubular neoplasms of the bile ducts.

    PubMed

    Katabi, Nora; Torres, Javiera; Klimstra, David S

    2012-11-01

    Although most tumors of the bile ducts are predominantly invasive, some have an exophytic pattern within the bile ducts; these intraductal papillary neoplasms usually have well-formed papillae at the microscopic level. In this study, however, we describe a novel type of intraductal neoplasm of the bile ducts with a predominantly tubular growth pattern and other distinctive features. Ten cases of biliary intraductal neoplasms with a predominantly tubular architecture were identified in the files of the Pathology Department at Memorial Sloan-Kettering Cancer Center from 1983 to 2006. For each of these cases we studied the clinical presentation, histologic and immunohistochemical features (9 cases only), and the clinical follow-up of the patients. Three male and 7 female patients (38 to 78 y) presented with obstructive jaundice or abdominal pain. Eight of the patients underwent a partial hepatectomy; 2 underwent a laparoscopic bile duct excision, followed by a pancreatoduodenectomy in one of them. The tumors range in size from 0.6 to 8.0 cm. The intraductal portions of the tumors (8 intrahepatic, 1 extrahepatic hilar, 1 common bile duct) were densely cellular and composed of back-to-back tubular glands and solid sheets with minimal papillary architecture. The cells were cuboidal to columnar with mild to moderate cytologic atypia. Foci of necrosis were present in the intraductal component in 6 cases. An extraductal invasive carcinoma component was present in 7 cases, composing <25% of the tumor in 4 cases, and >75% in 1 case. It was observed by immunohistochemical analysis that the tumor cells expressed CK19, CA19-9, MUC1, and MUC6 in most cases and that SMAD4 expression was retained. MUC2, MUC5AC, HepPar1, synaptophysin, chromogranin, p53, and CA125 were negative in all cases and most were negative for CEA-M and B72.3. Four patients were free of tumor recurrence after 7 to 85 months (average, 27 mo). Four patients with an invasive carcinoma component suffered

  7. 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.

  8. Spleen tyrosine kinase contributes to acute renal allograft rejection in the rat

    PubMed Central

    Ramessur Chandran, Sharmila; Tesch, Greg H; Han, Yingjie; Woodman, Naomi; Mulley, William R; Kanellis, John; Blease, Kate; Ma, Frank Y; Nikolic-Paterson, David J

    2015-01-01

    Kidney allografts induce strong T-cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (Syk) is expressed by most leucocytes, except mature T cells, and is involved in intracellular signalling following activation of the Fcγ-receptor, B-cell receptor and some integrins. A role for Syk signalling has been established in antibody-dependent native kidney disease, but little is known of Syk in acute renal allograft rejection. Sprague–Dawley rats underwent bilateral nephrectomy and received an orthotopic Wistar renal allograft. Recipient rats were treated with a Syk inhibitor (CC0482417, 30 mg/kg/bid), or vehicle, from 1 h before surgery until being killed 5 days later. Vehicle-treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (T cells, macrophages, neutrophils and NK cells) and deposition of IgM, IgG and C3. Immunostaining identified Syk expression by many infiltrating leucocytes. CC0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. CC0482417 failed to prevent T-cell infiltration and activation within the allograft. However, CC0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for Syk in acute renal allograft rejection. Syk inhibition may be a useful addition to T-cell-based immunotherapy in renal transplantation. PMID:25529862

  9. Tubular solid oxide fuel cell prospect

    SciTech Connect

    Veyo, S.E.

    1996-05-01

    Driven by technological achievement and rational projection of commercial product cost, expectations for tubular SOFC commercialization are improving. Tubular SOFCs have surpassed 7 yrs operation and have recently demonstrated remarkable toughness in thermal cycling. Customer-owned systems with 25 kW stacks utilizing air electrode supported (AES) cells continue to operate directly on natural gas without degradation after multiple thermal cycles and over 4000 hrs operation. AES cell operation at elevated pressure corroborates theoretical estimates of performance gain without evidence of deleterious effect. Commercial class AES cell of 22 mm dia and 1500 mm length, is now in production for application to 100 kW, 50% efficient (ac/LHV), atmospheric pressure systems. This same cell applied to pressurized systems in combination with conventional turbo machinery (gas turbines) can yield an efficiency approaching 70% for power plants as small as 5 MW. Total installed system cost for commercial 5 MW SOFC/CT units for distributed power generation and on-site cogeneration should approach $1000/kW. A major challenge is formation of funded projects to demonstrate at the turn of the century prototype MW class SOFC/CT combined cycle power plants and to complete the development of commercial fuel cell manufacturing processes.

  10. Tubular photobioreactor design for algal cultures.

    PubMed

    Molina, E; Fernández, J; Acién, F G; Chisti, Y

    2001-12-28

    Principles of fluid mechanics, gas-liquid mass transfer, and irradiance controlled algal growth are integrated into a method for designing tubular photobioreactors in which the culture is circulated by an airlift pump. A 0.2 m(3) photobioreactor designed using the proposed approach was proved in continuous outdoor culture of the microalga Phaeodactylum tricornutum. The culture performance was assessed under various conditions of irradiance, dilution rates and liquid velocities through the tubular solar collector. A biomass productivity of 1.90 g l(-1) d(-1) (or 32 g m(-2) d(-1)) could be obtained at a dilution rate of 0.04 h(-1). Photoinhibition was observed during hours of peak irradiance; the photosynthetic activity of the cells recovered a few hours later. Linear liquid velocities of 0.50 and 0.35 m s(-1) in the solar collector gave similar biomass productivities, but the culture collapsed at lower velocities. The effect of dissolved oxygen concentration on productivity was quantified in indoor conditions; dissolved oxygen levels higher or lower than air saturation values reduced productivity. Under outdoor conditions, for given levels of oxygen supersaturation, the productivity decline was greater outdoors than indoors, suggesting that under intense outdoor illumination photooxidation contributed to loss of productivity in comparison with productivity loss due to oxygen inhibition alone. Dissolved oxygen values at the outlet of solar collector tube were up to 400% of air saturation.

  11. Heme oxygenase-1 induction contributes to renoprotection by G-CSF during rhabdomyolysis-associated acute kidney injury.

    PubMed

    Wei, Qingqing; Hill, William D; Su, Yunchao; Huang, Shuang; Dong, Zheng

    2011-07-01

    Granulocyte colony-stimulating factor (G-CSF) is renoprotective during acute kidney injury (AKI) induced by ischemia and cisplatin nephrotoxicity; however, the underlying mechanism is not entirely clear. Rhabdomyolysis is another important clinical cause of AKI, due to the release of nephrotoxins (e.g., heme) from disrupted muscles. The current study has determined the effects of G-CSF on rhabdomyolysis-associated AKI using in vivo and in vitro models. In C57BL/6 mice, intramuscular injection of glycerol induced AKI, which was partially prevented by G-CSF pretreatment. Consistently, glycerol-induced renal tissue damage was ameliorated by G-CSF. In addition, animal survival following the glycerol injection was improved from ∼30 to ∼70% by G-CSF. In cultured renal tubular cells, hemin-induced apoptosis was also suppressed by G-CSF. Interestingly, G-CSF induced heme oxygenase-1 (HO-1, a critical enzyme for heme/hemin degradation and detoxification) in both cultured tubular cells and mouse kidneys. Blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) could largely diminish the protective effects of G-CSF. Together, these results demonstrated the renoprotective effects of G-CSF in rhabdomyolysis-associated AKI. Notably, G-CSF may directly protect against tubular cell injury under the disease condition by inducing HO-1.

  12. Etiopathology of chronic tubular, glomerular and renovascular nephropathies: clinical implications.

    PubMed

    López-Novoa, José M; Rodríguez-Peña, Ana B; Ortiz, Alberto; Martínez-Salgado, Carlos; López Hernández, Francisco J

    2011-01-20

    Chronic kidney disease (CKD) comprises a group of pathologies in which the renal excretory function is chronically compromised. Most, but not all, forms of CKD are progressive and irreversible, pathological syndromes that start silently (i.e. no functional alterations are evident), continue through renal dysfunction and ends up in renal failure. At this point, kidney transplant or dialysis (renal replacement therapy, RRT) becomes necessary to prevent death derived from the inability of the kidneys to cleanse the blood and achieve hydroelectrolytic balance. Worldwide, nearly 1.5 million people need RRT, and the incidence of CKD has increased significantly over the last decades. Diabetes and hypertension are among the leading causes of end stage renal disease, although autoimmunity, renal atherosclerosis, certain infections, drugs and toxins, obstruction of the urinary tract, genetic alterations, and other insults may initiate the disease by damaging the glomerular, tubular, vascular or interstitial compartments of the kidneys. In all cases, CKD eventually compromises all these structures and gives rise to a similar phenotype regardless of etiology. This review describes with an integrative approach the pathophysiological process of tubulointerstitial, glomerular and renovascular diseases, and makes emphasis on the key cellular and molecular events involved. It further analyses the key mechanisms leading to a merging phenotype and pathophysiological scenario as etiologically distinct diseases progress. Finally clinical implications and future experimental and therapeutic perspectives are discussed.

  13. WNT/β-Catenin Signaling Is Required for Integration of CD24+ Renal Progenitor Cells into Glycerol-Damaged Adult Renal Tubules

    PubMed Central

    Zhang, Zhao; Iglesias, Diana M.; Corsini, Rachel; Chu, LeeLee; Goodyer, Paul

    2015-01-01

    During development, nephron progenitor cells (NPC) are induced to differentiate by WNT9b signals from the ureteric bud. Although nephrogenesis ends in the perinatal period, acute kidney injury (AKI) elicits repopulation of damaged nephrons. Interestingly, embryonic NPC infused into adult mice with AKI are incorporated into regenerating tubules. Since WNT/β-catenin signaling is crucial for primary nephrogenesis, we reasoned that it might also be needed for the endogenous repair mechanism and for integration of exogenous NPC. When we examined glycerol-induced AKI in adult mice bearing a β-catenin/TCF reporter transgene, endogenous tubular cells reexpressed the NPC marker, CD24, and showed widespread β-catenin/TCF signaling. We isolated CD24+ cells from E15 kidneys of mice with the canonical WNT signaling reporter. 40% of cells responded to WNT3a in vitro and when infused into glycerol-injured adult, the cells exhibited β-catenin/TCF reporter activity when integrated into damaged tubules. When embryonic CD24+ cells were treated with a β-catenin/TCF pathway inhibitor (IWR-1) prior to infusion into glycerol-injured mice, tubular integration of cells was sharply reduced. Thus, the endogenous canonical β-catenin/TCF pathway is reactivated during recovery from AKI and is required for integration of exogenous embryonic renal progenitor cells into damaged tubules. These events appear to recapitulate the WNT-dependent inductive process which drives primary nephrogenesis. PMID:26089915

  14. The effect of wellbore curvature on tubular buckling and lockup

    SciTech Connect

    Wu, J.; Juvkam-Wold, H.C.

    1994-12-31

    This paper describes sinusoidal and helical buckling of tubulars in curved wellbores (such as the build section of horizontal wells) and the effect on `lockup` of tubulars when drilling horizontal or extended-reach wells. New buckling load equations are derived to properly predict sinusoidal and helical buckling of tubulars in such wellbores. The results show that the buckling loads to ultimate sinusoidal and helical buckling of tubulars in curved wellbores are usually much larger than those in straight wellbores. This is because the curved wellbore tends to hold the axially compressed tubular against the outer-curve side of the wellbore. It is difficult to buckle a tubular into a sinusoidal or helical shape in curved wellbores, unless a very high axial compressive load is applied. The risk of tubular lockup when chilling horizontal or extended-reach wells is therefore reduced, because there is likely to be very little, if any, tubular buckling in the curved wellbore. The buckling loads derived in this paper also agree with those in straight wellbores when wellbore curvature approaches zero. Small scale laboratory experiments confirmed the theoretically derived buckling loads.

  15. The tubular "cookie cutter" bullet: a unique projectile.

    PubMed

    Nolte, K B

    1990-11-01

    Recently marketed PMC (Pan Metal Corporation) Ultramag tubular hollow point ammunition is uniquely constructed with a two-part projectile composed of a tubular copper bullet and a Teflon wad. A fatal gunshot wound with this ammunition is described. A unique radiographic pattern and the results of test firing are also presented.

  16. Cadmium and lead in blood in relation to low bone mineral density and tubular proteinuria.

    PubMed Central

    Alfvén, Tobias; Järup, Lars; Elinder, Carl-Gustaf

    2002-01-01

    Long-term exposure to cadmium may cause kidney and bone damage. Urinary cadmium is commonly used as the dose estimate for the body burden of cadmium. However, elevated levels of cadmium in the urine may reflect not only high levels of cadmium dose but also renal dysfunction. In this study we used blood cadmium as the dose estimate. In addition, we analyzed blood lead. We examined 479 men and 542 women, ages 16-81 years, who were environmentally or occupationally exposed to cadmium and lead. We used urinary protein alpha 1-microglobulin as a marker for tubular proteinuria and measured forearm bone mineral density using dual-energy X-ray absorptiometry. The relationship between blood cadmium and tubular proteinuria was strong, even when we excluded occupationally exposed participants. The subgroup with the highest blood cadmium levels had a 4-fold risk of tubular proteinuria compared to the subgroup with the lowest blood cadmium levels. In the older age group (age > 60), the risk of low bone mineral density (z-score < -1) for the subgroup with the highest blood cadmium levels was almost 3-fold compared to the group with lowest blood cadmium levels. We found no similar associations for lead. The observed effects may be caused by higher cadmium exposure in the past. This study strengthens previous evidence that cadmium exposure may affect both bone mineral density and kidney function. PMID:12117647

  17. Micropatterning control of tubular commitment in human adult renal stem cells.

    PubMed

    Sciancalepore, Anna G; Portone, Alberto; Moffa, Maria; Persano, Luana; De Luca, Maria; Paiano, Aurora; Sallustio, Fabio; Schena, Francesco P; Bucci, Cecilia; Pisignano, Dario

    2016-07-01

    The treatment of renal injury by autologous, patient-specific adult stem cells is still an unmet need. Unsolved issues remain the spatial integration of stem cells into damaged areas of the organ, the commitment in the required cell type and the development of improved bioengineered devices. In this respect, biomaterials and architectures have to be specialized to control stem cell differentiation. Here, we perform an extensive study on micropatterned extracellular matrix proteins, which constitute a simple and non-invasive approach to drive the differentiation of adult renal progenitor/stem cells (ARPCs) from human donors. ARPCs are interfaced with fibronectin (FN) micropatterns, in the absence of exogenous chemicals or cellular reprogramming. We obtain the differentiation towards tubular cells of ARPCs cultured in basal medium conditions, the tubular commitment thus being specifically induced by micropatterned substrates. We characterize the stability of the tubular differentiation as well as the induction of a polarized phenotype in micropatterned ARPCs. Thus, the developed cues, driving the functional commitment of ARPCs, offer a route to recreate the microenvironment of the stem cell niche in vitro, that may serve, in perspective, for the development of ARPC-based bioengineered devices.

  18. Amino acid infusion blocks renal tubular uptake of an indium-labelled somatostatin analogue.

    PubMed Central

    Hammond, P. J.; Wade, A. F.; Gwilliam, M. E.; Peters, A. M.; Myers, M. J.; Gilbey, S. G.; Bloom, S. R.; Calam, J.

    1993-01-01

    The Indium-labelled somatostatin analogue pentetreotide has been successfully developed for imaging of somatostatin receptor positive tumours. However there is significant renal tubular uptake of the radiolabelled peptide, which can obscure upper abdominal tumours and would preclude its use for targeted radiotherapy. The aim of this study was to determine whether amino acid infusion, which has been shown to block renal tubular peptide reabsorption, diminishes renal parenchymal uptake of this radiolabelled analogue. Eight patients being scanned with the 111In-labelled somatostatin analogue, pentetreotide, for localisation of gastroenteropancreatic tumours received an infusion of synthetic amino acids. The ratio of isotope uptake in kidney to that in spleen was assessed, and compared to the ratio for matched control patients, to determine if amino acid infusion reduced renal parenchymal uptake of the radiopharmaceutical. The amount of isotope in the urine was determined to ensure that any effect of the amino acid infusion was unrelated to changes in clearance. Infusion of amino acids significantly reduced renal parenchymal uptake of isotope at 4 h. There was a non-significant increase in urinary clearance of isotope over the 4 h, consistent with reduced reuptake and a lack of effect on glomerular filtration rate. This technique, by preventing renal damage, may allow the use of this somatostatin analogue for local radiotherapy, and could be of wider value in blocking tubular re-uptake of potentially nephrotoxic agents, such as radiolabelled Fab fragments. Images Figure 1 PMID:8099808

  19. 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

  20. Protective Effects of Luteolin on Lipopolysaccharide-Induced Acute Renal Injury in Mice

    PubMed Central

    Xin, Shao-bin; Yan, Hao; Ma, Jing; Sun, Qiang; Shen, Li

    2016-01-01

    Background Sepsis can cause serious acute kidney injury in bacterium-infected patients, especially in intensive care patients. Luteolin, a bioactive flavonoid, has renal protection and anti-inflammatory effects. This study aimed to investigate the effect and underlying mechanism of luteolin in attenuating lipopolysaccharide (LPS)-induced renal injury. Material/Methods ICR mice were treated with LPS (25 mg/kg) with or without luteolin pre-treatment (40 mg/kg for three days). The renal function, histological changes, degree of oxidative stress, and tubular apoptosis in these mice were examined. The effects of luteolin on LPS-induced expression of renal tumor necrosis factor-α (TNF-α), NF-κB, MCP-1, ICAM-1, and cleaved caspase-3 were evaluated. Results LPS resulted in rapid renal damage of mice, increased level of blood urea nitrogen (BUN), and serum creatinine (Scr), tubular necrosis, and increased oxidative stress, whereas luteolin pre-treatment could attenuate this renal damage and improve the renal functions significantly. Treatment with LPS increased TNF-α, NF-κB, IL-1β, cleaved caspase-3, MCP-1, and ICAM-1 expression, while these disturbed expressions were reversed by luteolin pre-treatment. Conclusions These results indicate that luteolin ameliorates LPS-mediated nephrotoxicity via improving renal oxidant status, decreasing NF-κB activation and inflammatory and apoptosis factors, and then disturbing the expression of apoptosis-related proteins. PMID:28029146

  1. Protective effects of icariin on cisplatin-induced acute renal injury in mice

    PubMed Central

    Ma, Pei; Zhang, Sen; Su, Xinlin; Qiu, Guixing; Wu, Zhihong

    2015-01-01

    Cisplatin chemotherapy often causes acute kidney injury in cancer patients. Icariin is a bioactive flavonoid, which has renal protection and anti-inflammation effects. This study investigated the mechanism underlying the attenuation of cisplatin-induced renal injury by icariin. BALB/c mice were treated with cisplatin (15 mg/kg) with or without treatment with icariin (30 or 60 mg/kg for 5 days). Renal function, histological changes, degree of oxidative stress and tubular apoptosis were examined. The effects of icariin on cisplatin-induced expression of renal TNF-α, NF-κB, cleaved caspase-3 and Bcl-2 family proteins were evaluated. Treatment of mice with cisplatin resulted in renal damage, showing an increase in blood urea nitrogen and creatinine levels, tubular damage, oxidative stress and apoptosis. These renal changes could be significantly improved by icariin treatment, especially in high dose of icariin group. Examination of molecules involving inflammation and apoptosis of the kidney revealed that treatment of icariin reduced expression of TNF-α, NF-κB, cleaved caspase-3, and Bax, increased the expression of BCL-2. These results indicate that icariin ameliorates the cisplatin-mediated nephrotoxicity via improving renal oxidant status, consequent NF-κB activation and inflammation cascade and apoptosis, and the following disturbed expression of apoptosis related proteins. PMID:26692955

  2. Cyclic capacity of tubular beam-columns with local buckling: Numerical and experimental studies

    SciTech Connect

    Skallerud, B.; Amdahl, J.; Johansen, A.; Eide, O.I.

    1996-12-31

    The present investigation addresses the cyclic capacity of tubular members subjected to both local and global buckling during cyclic loading. Diameter to thickness ratios of 45 and 60 are studied. The performance of FE models, both a beam model and shell model, is compared to test results in terms of load versus displacement behavior and energy accumulation. Some problems regarding the prediction of local strain histories in the local buckle zone are pointed out. Damage accumulation models in terms of energy per cycle are discussed, aiming at possible member detachment criteria.

  3. The intensive care medicine agenda on acute kidney injury.

    PubMed

    Pickkers, Peter; Ostermann, Marlies; Joannidis, Michael; Zarbock, Alexander; Hoste, Eric; Bellomo, Rinaldo; Prowle, John; Darmon, Michael; Bonventre, Joseph V; Forni, Lui; Bagshaw, Sean M; Schetz, Miet

    2017-01-30

    Acute kidney injury (AKI) is a common complication in the critically ill. Current standard of care mainly relies on identification of patients at risk, haemodynamic optimization, avoidance of nephrotoxicity and the use of renal replacement therapy (RRT) in established AKI. The detection of early biomarkers of renal tissue damage is a recent development that allows amending the late and insensitive diagnosis with current AKI criteria. Increasing evidence suggests that the consequences of an episode of AKI extend long beyond the acute hospitalization. Citrate has been established as the anticoagulant of choice for continuous RRT. Conflicting results have been published on the optimal timing of RRT and on the renoprotective effect of remote ischaemic preconditioning. Recent research has contradicted that acute tubular necrosis is the common pathology in AKI, that septic AKI is due to global kidney hypoperfusion, that aggressive fluid therapy benefits the kidney, that vasopressor therapy harms the kidney and that high doses of RRT improve outcome. Remaining uncertainties include the impact of aetiology and clinical context on pathophysiology, therapy and prognosis, the clinical benefit of biomarker-driven interventions, the optimal mode of RRT to improve short- and long-term patient and kidney outcomes, the contribution of AKI to failure of other organs and the optimal approach for assessing and promoting renal recovery. Based on the established gaps in current knowledge the trials that must have priority in the coming 10 years are proposed together with the definition of appropriate clinical endpoints.

  4. Flexible tubular replicas of abdominal aortic aneurysms.

    PubMed

    Berry, E; Marsden, A; Dalgarno, K W; Kessel, D; Scott, D J A

    2002-01-01

    The aim of this study was to manufacture life-size, flexible, tubular replicas of human abdominal aortic aneurysms and the associated vasculature, suitable for use in a training simulator for endovascular procedures. Selective laser sintering was used to create a geometrically correct master model for each of ten anatomical variations. The masters were used to generate flexible latex replicas. The use of the replicas in the training simulator was demonstrated. In total ten silicone rubber models were produced. When connected into the training simulator and perfused at arterial pressure it was possible to deploy an endovascular stent under fluoroscopic control and to perform angiography. The study has shown that conventional rapid prototyping technology can be used to manufacture flexible, radiolucent replicas which provide a realistic training environment for endovascular procedures.

  5. Pain Medicines and Kidney Damage

    MedlinePlus

    ... Work Kidney Disease A-Z Pain Medicine and Kidney Damage An analgesic is any medicine intended to ... of chronic kidney disease called analgesic nephropathy. Acute Kidney Failure Some patient case reports have attributed incidents ...

  6. Resveratrol attenuates acute kidney injury by inhibiting death receptor-mediated apoptotic pathways in a cisplatin-induced rat model

    PubMed Central

    Hao, Qiufa; Xiao, Xiaoyan; Zhen, Junhui; Feng, Jinbo; Song, Chun; Jiang, Bei; Hu, Zhao

    2016-01-01

    Acute kidney injury is a clinical syndrome characterized by a loss of renal function and acute tubular necrosis. Resveratrol exerts a wide range of pharmacological effects based on its anti-inflammatory, antioxidant and cytoprotective properties. The present study aimed to evaluate whether resveratrol attenuates acute kidney injury in a cisplatin-induced rat model and to investigate the potential mechanisms involved. Rats were randomly divided into four treatment groups: Control, cisplatin, resveratrol, and cisplatin plus resveratrol. Rats exposed to cisplatin displayed acute kidney injury, identified by analysis of renal function and histopathological observation. Resveratrol significantly ameliorated the increased serum creatinine, blood urea nitrogen, renal index and histopathological damage induced by cisplatin. Furthermore, compared with untreated control animals, cisplatin lead to significantly increased expression of Fas ligand, tumor necrosis factor-α (TNF-α), caspase-8 and Bcl-2 associated protein X apoptosis regulator (Bax), and decreased expression of anti-apoptosis regulators, BH3 interacting domain death agonist (BID) and B cell lymphoma 2 apoptosis regulator (Bcl-2). Administration of resveratrol significantly reversed the cisplatin-induced alteration in these apoptosis-associated proteins. In conclusion, these findings suggest that resveratrol attenuates cisplatin-induced acute kidney injury through inactivation of the death receptor-mediated apoptotic pathway, and may provide a new therapeutic strategy to ameliorate the process of acute kidney injury. PMID:27600998

  7. Tubular reabsorption in normal renal function.

    PubMed

    O'Connor, W J

    1984-01-01

    The purpose here is to examine in relation to normal renal function three factors which might affect tubular reabsorption: (1) The reabsorption of SO4, PO4, K, Cl, HCO3 and water are all linked to the reabsorption of Na. This would amount to the reabsorption by the tubules of a net reabsorbate of a composition similar to Locke's fluid. Fixed linkage of the reabsorption of a substance to the reabsorption of Na would be a very effective way of maintaining its plasma concentration within a narrow range. The substance would be retained unless its plasma concentration exceeds a threshold value and then small increase in plasma concentration determines its excretion. (2) The rate of reabsorption of Na and substances linked to it is increased when the volume of the intraluminal fluid is increased. This would explain why there is only a small increase in the excretion of Na and other electrolytes when glomerular filtration rate is increased after a meal of meat. (3) Plasma protein concentration affects tubular reabsorption. This would explain why fall in plasma protein is a main agent determining Na excretion in normal animals. Trying to see 'how far the observed facts can be brought into accord with a theory' reveals the difficulty of applying critical tests. On the one hand, the theories are not stated quantitatively in reference to the small changes of normal life; rather the evidence is from experiments with large changes. On the other hand, the small changes within the range of normal function, while themselves statistically significant, are too small for effective investigation of circumstances which may modify them. In the examples discussed here, we cannot say more than that the theories could explain the facts and their participation cannot be excluded.

  8. Detection and evaluation of renal biomarkers in a swine model of acute myocardial infarction and reperfusion.

    PubMed

    Duan, Su-Yan; Xing, Chang-Ying; Zhang, Bo; Chen, Yan

    2015-01-01

    The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS.

  9. 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

  10. Pravastatin inhibits advanced glycation end products (AGEs)-induced proximal tubular cell apoptosis and injury by reducing receptor for AGEs (RAGE) level.

    PubMed

    Ishibashi, Yuji; Yamagishi, Sho-ichi; Matsui, Takanori; Ohta, Keisuke; Tanoue, Ryuichiro; Takeuchi, Masayoshi; Ueda, Seiji; Nakamura, Kei-ichiro; Okuda, Seiya

    2012-08-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) axis play a role in diabetic nephropathy. Statins have been shown to ameliorate renal function and reduce proteinuria in patients with chronic kidney disease. However, the effects of statin on AGEs-induced tubular cell damage remain unknown. We examined here whether and how pravastatin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was analyzed in an enzyme-linked immunosorbent assay. Asymmetric dimethylarginine (ADMA) expression was evaluated by immunostaining. Pravastatin dose-dependently inhibited the AGEs-induced up-regulation of RAGE mRNA level, ROS generation and apoptosis in human renal proximal tubular cells. Further, AGEs decreased mRNA level of dimethylarginine dimethylaminohydrolase-2, an enzyme that mainly degrades asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase and subsequently increased ADMA generation in tubular cells, both of which were also prevented by pravastatin. Geranylgeranyl pyrophosphate (GGPP) treatment blocked all of the effects of pravastatin on tubular cells. We found that rosuvastatin also significantly blocked the AGEs-induced increase in RAGE mRNA level and ROS generation, both of which were prevented by GGPP. Our present study suggests that pravastatin could inhibit the AGEs-induced apoptosis and ADMA generation in tubular cells by suppressing RAGE expression probably via inhibition of GGPP synthesis. Pravastatin may exert beneficial effects on tubular damage in diabetic nephropathy by blocking the AGEs-RAGE axis.

  11. Blockade of KCa3.1 potassium channels protects against cisplatin-induced acute kidney injury.

    PubMed

    Chen, Cheng-Lung; Liao, Jiunn-Wang; Hu, Oliver Yoa-Pu; Pao, Li-Heng

    2016-09-01

    Tubular cell apoptosis significantly contributes to cisplatin-induced acute kidney injury (AKI) pathogenesis. Although KCa3.1, a calcium-activated potassium channel, participates in apoptosis, its involvement in cisplatin-induced AKI is unknown. Here, we found that cisplatin treatment triggered an early induction of KCa3.1 expression associated with HK-2 cell apoptosis, the development of renal tubular damage, and apoptosis in mice. Treatment with the highly selective KCa3.1 blocker TRAM-34 suppressed cisplatin-induced HK-2 cell apoptosis. We further assessed whether KCa3.1 mediated cisplatin-induced AKI in genetic knockout and pharmacological blockade mouse models. KCa3.1 deficiency reduced renal function loss, renal tubular damage, and the induction of the apoptotic marker caspase-3 in the kidneys of cisplatin-treated KCa3.1 (-/-) mice. Pharmacological blockade of KCa3.1 by TRAM-34 similarly attenuated cisplatin-induced AKI in mice. Furthermore, we dissected the mechanisms underlying cisplatin-induced apoptosis reduction via KCa3.1 blockade. We found that KCa3.1 blockade attenuated cytochrome c release and the increase in the intrinsic apoptotic mediators Bax, Bak, and caspase-9 after cisplatin treatment. KCa3.1 blocking inhibited the cisplatin-induced activation of the endoplasmic reticulum (ER) stress mediator caspase-12, which is independent of calcium-dependent protease m-calpain activation. Taken together, KCa3.1 blockade protects against cisplatin-induced AKI through the attenuation of apoptosis by interference with intrinsic apoptotic and ER stress-related mediators, providing a potential target for the prevention of cisplatin-induced AKI.

  12. Nobiletin ameliorates cisplatin-induced acute kidney injury due to its anti-oxidant, anti-inflammatory and anti-apoptotic effects.

    PubMed

    Malik, Salma; Bhatia, Jagriti; Suchal, Kapil; Gamad, Nanda; Dinda, Amit Kumar; Gupta, Yogender Kumar; Arya, Dharamvir Singh

    2015-01-01

    Cisplatin is an effective anti-cancer drug which causes remarkable toxicity to kidney by generating reactive oxygen species and by stimulating inflammatory and apoptotic pathway. Citrus flavonoid, like nobiletin has been reported to possess anti-oxidant, anti-inflammatory and anti-apoptotic properties. Hence, the present study was aimed to evaluate these properties of nobiletin, a polymethoxy flavone in cisplatin-induced acute renal injury. Adult male albino Wistar rats were divided into 6 groups. Nobiletin was administered at the dose of 1.25, 2.5 and 5mg/kg for a period of 10 days. On 7th day, a single injection of cisplatin (8 mg/kg) was injected to rats. Cisplatin administration resulted in renal dysfunction as evident by increase in serum creatinine and BUN levels. Oxidative stress in cisplatin group was reflected by increase in MDA level, and depletion of anti-oxidants such as glutathione, superoxide dismutase and catalase in renal tissue. Furthermore, cisplatin increased the expressions of Bax, caspase-3 and DNA damage along with decreased expression of Bcl-2 in the renal tissue. Histological analysis also revealed acute tubular necrosis. However, pretreatment with nobiletin preserved renal function and restored anti-oxidant status. Nobiletin supplementation inhibited activation of apoptotic pathways and DNA damage. It also attenuated tubular injury histologically. Collectively, the result of this study suggests the nephroprotective potential of nobiletin which may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

  13. Inherited complement regulatory protein deficiency predisposes to human disease in acute injury and chronic inflammatory statesthe examples of vascular damage in atypical hemolytic uremic syndrome and debris accumulation in age-related macular degeneration.

    PubMed

    Richards, Anna; Kavanagh, David; Atkinson, John P

    2007-01-01

    In this chapter, we examine the role of complement regulatory activity in atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). These diseases are representative of two distinct types of complement-mediated injury, one being acute and self-limited, the other reflecting accumulation of chronic damage. Neither condition was previously thought to have a pathologic relationship to the immune system. However, alterations in complement regulatory protein genes have now been identified as major predisposing factors for the development of both diseases. In aHUS, heterozygous mutations leading to haploinsufficiency and function-altering polymorphisms in complement regulators have been identified, while in AMD, polymorphic haplotypes in complement genes are associated with development of disease. The basic premise is that a loss of function in a plasma or membrane inhibitor of the alternative complement pathway allows for excessive activation of complement on the endothelium of the kidney in aHUS and on retinal debris in AMD. These associations have much to teach us about the host's innate immune response to acute injury and to chronic debris deposition. We all experience cellular injury and, if we live long enough, will deposit debris in blood vessel walls (atherosclerosis leading to heart attacks and strokes), the brain (amyloid proteins leading to Alzheimer's disease), and retina (lipofuscin pigments leading to AMD). These are three common causes of morbidity and mortality in the developed world. The clinical, genetic, and immunopathologic understandings derived from the two examples of aHUS and AMD may illustrate what to anticipate in related conditions. They highlight how a powerful recognition and effector system, the alternative complement pathway, reacts to altered self. A response to acute injury or chronic debris accumulation must be appropriately balanced. In either case, too much activation or too little regulation promotes

  14. Erythropoietin reduces cumulative nephrotoxicity from cisplatin and enhances renal tubular cell proliferation.

    PubMed

    Zafirov, Dimce; Petrusevska, G; Sikole, Aleksandar; Trojacanec, J; Labacevski, N; Kostova, E; Jakovski, K; Atanasovska, E; Petrov, S

    2008-12-01

    Cisplatin, a heavy metal complex, is one of the most active drugs used in the treatment of several human malignancies. However, high-dose therapy with cisplatin is limited by its cumulative nephrotoxicity. The main objectives of this study were to determine the role of recombinant human erythropoietin (Epoetin alfa) in the prevention of nephrotoxicity induced experimentally in Wistar rats by long-term administration of cisplatin (2 mg/kg/b.w./week) over eight weeks, and an evaluation of its effect on renal tubular cell proliferation. The animals were randomly assigned into three groups, each including 25 rats. Group 1 (CP) received only cisplatin (2 mg/kg/b.w./week), group 2 (CP+EPO) received cisplatin (2 mg/kg/b.w./week) and epoetin alfa (150 IE/kg/b.w./three times a week), and group 3 (control group) received only saline. During the study, the following tests for the assessment of the renal function and renal damages were performed: determination of concentration of serum creatinine and BUN and determination of total protein quantity in 24-hour urine samples. At the end of the study, the abdomen was opened and both kidneys of the rats were removed and sent for histological and morphometric analysis. Ki-67 was used as a tool to determine a proliferative index. The results obtained have shown that epoetin alfa significantly reduced the functional renal failures and renal damages, and increased toleration of high doses of cisplatin. At the same time, our results with regard to tubular proliferative index have confirmed that one of the possible mechanisms by which erythropoietin accomplishes its renoprotective effect is stimulation of tubular cell proliferation and regeneration.

  15. Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP

    PubMed Central

    Mukherjee, Rajarshi; Mareninova, Olga A; Odinokova, Irina V; Huang, Wei; Murphy, John; Chvanov, Michael; Javed, Muhammad A; Wen, Li; Booth, David M; Cane, Matthew C; Awais, Muhammad; Gavillet, Bruno; Pruss, Rebecca M; Schaller, Sophie; Molkentin, Jeffery D; Tepikin, Alexei V; Petersen, Ole H; Pandol, Stephen J; Gukovsky, Ilya; Criddle, David N; Gukovskaya, Anna S

    2016-01-01

    Objective Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. Design We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. Results MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. Conclusions This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease. PMID:26071131

  16. The role of the pericardium in the valveless, tubular heart of the tunicate Ciona savignyi.

    PubMed

    Waldrop, Lindsay D; Miller, Laura A

    2015-09-01

    Tunicates, small invertebrates within the phylum Chordata, possess a robust tubular heart which pumps blood through their open circulatory systems without the use of valves. This heart consists of two major components: the tubular myocardium, a flexible layer of myocardial cells that actively contracts to drive fluid down the length of the tube; and the pericardium, a stiff, outer layer of cells that surrounds the myocardium and creates a fluid-filled space between the myocardium and the pericardium. We investigated the role of the pericardium through in vivo manipulations on tunicate hearts and computational simulations of the myocardium and pericardium using the immersed boundary method. Experimental manipulations reveal that damage to the pericardium results in aneurysm-like bulging of the myocardium and major reductions in the net blood flow and percentage closure of the heart's lumen during contraction. In addition, varying the pericardium-to-myocardium (PM) diameter ratio by increasing damage severity was positively correlated with peak dye flow in the heart. Computational simulations mirror the results of varying the PM ratio experimentally. Reducing the stiffness of the myocardium in the simulations reduced mean blood flow only for simulations without a pericardium. These results indicate that the pericardium has the ability to functionally increase the stiffness of the myocardium and limit myocardial aneurysms. The pericardium's function is likely to enhance flow through the highly resistive circulatory system by acting as a support structure in the absence of connective tissue within the myocardium.

  17. Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both CDK4/6 and OCT2 functions.

    PubMed

    Pabla, Navjotsingh; Gibson, Alice A; Buege, Mike; Ong, Su Sien; Li, Lie; Hu, Shuiying; Du, Guoqing; Sprowl, Jason A; Vasilyeva, Aksana; Janke, Laura J; Schlatter, Eberhard; Chen, Taosheng; Ciarimboli, Giuliano; Sparreboom, Alex

    2015-04-21

    Acute kidney injury (AKI) is a potentially fatal syndrome characterized by a rapid decline in kidney function caused by ischemic or toxic injury to renal tubular cells. The widely used chemotherapy drug cisplatin accumulates preferentially in the renal tubular cells and is a frequent cause of drug-induced AKI. During the development of AKI the quiescent tubular cells reenter the cell cycle. Strategies that block cell-cycle progression ameliorate kidney injury, possibly by averting cell division in the presence of extensive DNA damage. However, the early signaling events that lead to cell-cycle activation during AKI are not known. In the current study, using mouse models of cisplatin nephrotoxicity, we show that the G1/S-regulating cyclin-dependent kinase 4/6 (CDK4/6) pathway is activated in parallel with renal cell-cycle entry but before the development of AKI. Targeted inhibition of CDK4/6 pathway by small-molecule inhibitors palbociclib (PD-0332991) and ribociclib (LEE011) resulted in inhibition of cell-cycle progression, amelioration of kidney injury, and improved overall survival. Of additional significance, these compounds were found to be potent inhibitors of organic cation transporter 2 (OCT2), which contributes to the cellular accumulation of cisplatin and subsequent kidney injury. The unique cell-cycle and OCT2-targeting activities of palbociclib and LEE011, combined with their potential for clinical translation, support their further exploration as therapeutic candidates for prevention of AKI.

  18. Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models

    PubMed Central

    2016-01-01

    Contrast-induced acute kidney injury (CI-AKI) can occur in 3–25% of patients receiving radiocontrast material (RCM) despite appropriate preventive measures. Often patients with an atherosclerotic vasculature have to receive large doses of RCM. Thus, animal studies to uncover the exact pathomechanism of CI-AKI are needed. Sensitive and specific histologic end-points are lacking; thus in the present review we summarize the histologic appearance of different rodent models of CI-AKI. Single injection of RCM causes overt renal damage only in rabbits. Rats and mice need an additional insult to the kidney to establish a clinically manifest CI-AKI. In this review we demonstrate that the concentrating ability of the kidney may be responsible for species differences in sensitivity to CI-AKI. The most commonly held theory about the pathomechanism of CI-AKI is tubular cell injury due to medullary hypoxia. Thus, the most common additional insult in rats and mice is some kind of ischemia. The histologic appearance is tubular epithelial cell (TEC) damage; however severe TEC damage is only seen if RCM is combined by additional ischemia. TEC vacuolization is the first sign of CI-AKI, as it is a consequence of RCM pinocytosis and lysosomal fusion; however it is not sensitive as it does not correlate with renal function and is not specific as other forms of TEC damage also cause vacuolization. In conclusion, histopathology alone is insufficient and functional parameters and molecular biomarkers are needed to closely monitor CI-AKI in rodent experiments. PMID:27975052

  19. Characterisation of human tubular cell monolayers as a model of proximal tubular xenobiotic handling

    SciTech Connect

    Brown, Colin D.A. Sayer, Rachel; Windass, Amy S.; Haslam, Iain S.; Broe, Marc E. de; D'Haese, Patrick C.; Verhulst, Anja

    2008-12-15

    The aim of this study was to determine whether primary human tubular cell monolayers could provide a powerful tool with which to investigate the renal proximal tubular handling of xenobiotics. Human proximal and distal tubule/collecting duct cells were grown as monolayers on permeable filter supports. After 10 days in culture, proximal tubule cells remained differentiated and expressed a wide palette of transporters at the mRNA level including NaPi-IIa, SGLT1, SGLT2, OCT2, OCTN2, OAT1, OAT3, OAT4, MDR1, MRP2 and BCRP. At the protein level, the expression of a subset of transporters including NaPi-IIa, OAT1 and OAT3 was demonstrated using immunohistochemistry. Analysis of the expression of the ATP binding cassette efflux pumps MDR1, MRP2 and BCRP confirmed their apical membrane localisation. At the functional level, tubule cell monolayers retain the necessary machinery to mediate the net secretion of the prototypic substrates; PAH and creatinine. PAH secretion across the monolayer consisted of the uptake of PAH across the basolateral membrane by OAT1 and OAT3 and the apical exit of PAH by a probenecid and MK571-sensitive route consistent with actions of MRP2 or MRP4. Creatinine secretion was by OCT2-mediated uptake at the basolateral membrane and via MDR1 at the apical membrane. Functional expression of MDR1 and BCRP at the apical membrane was also demonstrated using a Hoechst 33342 dye. Similarly, measurement of calcein efflux demonstrated the functional expression of MRP2 at the apical membrane of cell monolayers. In conclusion, human tubular cell monolayers provide a powerful tool to investigate renal xenobiotic handling.

  20. 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)

  1. 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}

  2. 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.

  3. 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.

  4. 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.

  5. Energy production with a tubular propeller turbine

    NASA Astrophysics Data System (ADS)

    Samora, I.; Hasmatuchi, V.; Münch-Alligné, C.; Franca, M. J.; Schleiss, A. J.; Ramos, H. M.

    2016-11-01

    Micro-hydropower is a way of improving the energetic efficiency of existent water systems. In the particular case of drinking water systems, several studies have showed that pressure reducing valves can be by-passed with turbines in order to recover the dissipated hydraulic energy to produce electricity. As conventional turbines are not always cost-effective for power under 20 kW, a new energy converter is studied. A five blade tubular propeller (5BTP), assessed through laboratorial tests on a reduced model with a diameter of 85 mm diameter and a maximal output power of 300 W, is addressed in this work. Having showed promising potential for further development, since global efficiencies of around 60% were observed, the turbine has been further used to estimate the potential for energy production in a real case study. A sub-grid of the drinking water system of the city of Lausanne, Switzerland, has been used to obtain an annual energy production through hourly simulations with several turbines.

  6. 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.

  7. Status of tubular SOFC field unit demonstrations

    NASA Astrophysics Data System (ADS)

    George, Raymond A.

    Siemens Westinghouse is in the final stage of its tubular solid oxide fuel cell (SOFC) development program, and the program emphasis has shifted from basic technology development to cost reduction, scale-up and demonstration of pre-commercial power systems at customer sites. This paper describes our field unit demonstration program including the EDB/ELSAM 100-kW e combined heat and power (CHP) system, the Southern California Edison (SCE) 220-kW e pressurized SOFC/gas turbine (PSOFC/GT) power system, and the planned demonstrations of commercial prototype power systems. In the Spring of 1999, the EDB/ELSAM 100-kW e SOFC-CHP system produced 109 kW e net AC to the utility grid at 46% electrical efficiency and 65 kW t to the hot water district heating system, verifying the analytical predictions. The SCE 220-kW e PSOFC/GT power system will undergo factory startup in the Fall of 1999.

  8. 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.

  9. 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

  10. 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.

  11. Transient Distal Renal Tubular Acidosis in Organophosphate Poisoning

    PubMed Central

    Narayan, Ram; Abdulla, Mansoor C.; Alungal, Jemshad

    2017-01-01

    Renal complications due to organophosphate poisoning are very rare. We are presenting a unique case of transient distal renal tubular acidosis due to organophosphate poisoning, which to the best of our knowledge is the first of its kind. An elderly female after deliberate self-harm with ingestion of chlorpyrifos had multiple ventricular arrhythmias due to hypokalemia secondary to distal renal tubular acidosis which improved completely after treatment.

  12. A cut-off tubular geometry of loop space

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Partha

    Motivated by the computation of loop space quantum mechanics as indicated in [14], here we seek a better understanding of the tubular geometry of loop space ℒℳ corresponding to a Riemannian manifold ℳ around the submanifold of vanishing loops. Our approach is to first compute the tubular metric of (ℳ2N+1) C around the diagonal submanifold, where (ℳN) C is the Cartesian product of N copies of ℳ with a cyclic ordering. This gives an infinite sequence of tubular metrics such that the one relevant to ℒℳ can be obtained by taking the limit N →∞. Such metrics are computed by adopting an indirect method where the general tubular expansion theorem of [21] is crucially used. We discuss how the complete reparametrization isometry of loop space arises in the large-N limit and verify that the corresponding Killing equation is satisfied to all orders in tubular expansion. These tubular metrics can alternatively be interpreted as some natural Riemannian metrics on certain bundles of tangent spaces of ℳ which, for ℳ×ℳ, is the tangent bundle Tℳ.

  13. 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.

  14. Apoptosis of the Thick Ascending Limb Results in Acute Kidney Injury

    PubMed Central

    Srichai, Manakan B.; Hao, Chuanming; Davis, Linda; Golovin, Anastasia; Zhao, Min; Moeckel, Gilbert; Dunn, Steve; Bulus, Nada; Harris, Raymond C.; Zent, Roy; Breyer, Matthew D.

    2008-01-01

    Ischemia- or toxin-induced acute kidney injury is generally thought to affect the cells of the proximal tubule, but it has been difficult to define the involvement of other tubular segments because of the widespread damage caused by ischemia/reperfusion or toxin-induced injury in experimental models. For evaluation of whether thick ascending limb (TAL)-specific epithelial injury results in acute kidney injury, a novel transgenic mouse model that expresses the herpes simplex virus 1 thymidine kinase gene under the direction of the TAL-specific Tamm-Horsfall protein promoter was generated. After administration of gancyclovir, these mice demonstrated apoptosis only in TAL cells, with little evidence of neutrophil infiltration. Compared with control mice, blood urea nitrogen and creatinine levels were at least five-fold higher in the transgenic mice, which also developed oliguria and impaired urinary concentrating ability. These findings suggest that acute injury targeted only to the TAL is sufficient to cause severe acute kidney injury in mice with features similar to those observed in humans. PMID:18495962

  15. Apoptosis of the thick ascending limb results in acute kidney injury.

    PubMed

    Srichai, Manakan B; Hao, Chuanming; Davis, Linda; Golovin, Anastasia; Zhao, Min; Moeckel, Gilbert; Dunn, Steve; Bulus, Nada; Harris, Raymond C; Zent, Roy; Breyer, Matthew D

    2008-08-01

    Ischemia- or toxin-induced acute kidney injury is generally thought to affect the cells of the proximal tubule, but it has been difficult to define the involvement of other tubular segments because of the widespread damage caused by ischemia/reperfusion or toxin-induced injury in experimental models. For evaluation of whether thick ascending limb (TAL)-specific epithelial injury results in acute kidney injury, a novel transgenic mouse model that expresses the herpes simplex virus 1 thymidine kinase gene under the direction of the TAL-specific Tamm-Horsfall protein promoter was generated. After administration of gancyclovir, these mice demonstrated apoptosis only in TAL cells, with little evidence of neutrophil infiltration. Compared with control mice, blood urea nitrogen and creatinine levels were at least five-fold higher in the transgenic mice, which also developed oliguria and impaired urinary concentrating ability. These findings suggest that acute injury targeted only to the TAL is sufficient to cause severe acute kidney injury in mice with features similar to those observed in humans.

  16. [Biomarkers of acute kidney injury: a « trending topic » in cirrhosis].

    PubMed

    Barreto, Rogelio; Guevara, Mónica

    2013-01-01

    Acute kidney injury (AKI) is an ominous event in the natural history of cirrhosis. The differential diagnosis of this entity is hampered by the absence of specific biomarkers of tubular damage in cirrhosis. The clinical usefulness of such biomarkers is determined by their effectiveness in the diagnosis of AKI and their ability to provide critical information to ameliorate clinical outcomes and survival. The lack of biomarkers has hindered the development of interventions aimed to improve the prognosis of kidney impairment in cirrhosis. Currently, biomarkers are an area of intense research in nephrology. Emerging genomic and proteomic technologies have revealed novel plasma and urinary biomarkers of AKI. The present article discusses the most promising candidate biomarkers with potential application in cirrhosis, such as NGAL, KIM-1, cystatin-C, IL-18, L-FABP, N-acetyl glucosaminidase and netrin-1, are discussed below.

  17. Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2015-01-01

    Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure.

  18. Effects of Arctium lappa on Cadmium-Induced Damage to the Testis and Epididymis of Adult Wistar Rats.

    PubMed

    Predes, Fabricia de Souza; Diamante, M A S; Foglio, M A; Dolder, H

    2016-10-01

    The protective role of Arctium lappa (AL) on the testes of rats acutely exposed to cadmium (Cd) was tested. The rats were randomly divided into a control group (C-group) and three major experimental groups, which were further subdivided into minor groups (n = 6) according to the experimental period (7 or 56 days). The C-group was subdivided into C-7 and C-56 [receiving a single saline solution, intraperitoneal (i.p.), on the first day]; the AL-group, AL-7, and AL-56, received AL extract (300 mg/kg/daily); the Cd group, Cd-7 and Cd-56, received a single i.p. dose of CdCl2 (1.2 mg/kg body weight (BW)) on the first day; the CdAL group, CdAL-7 and CdAL-56, received the same Cd dose, followed by AL extract. Water or AL extract was administered daily by gavage. After either 7 or 56 days, the testis and accessory glands were removed after whole-body perfusion. Exposure to Cd and CdAL decreased the weight of the testis and epididymis, the gonadosomatic index, seminiferous tubular (ST) diameter, and ST volumetric proportion, and increased the volumetric proportion of interstitium after 56 days. In the epididymis caput, the tubular volumetric proportion decreased along with an increase of interstitial volumetric proportion and epithelium height after 56 days. The alterations observed were less severe only after 7 days. A progressive testicular damage resulted mainly in tubules lined only by Sertoli cells. The sperm number and cell debris decreased in the epididymis. We demonstrated that the testicular damage induced by single acute i.p. exposure to Cd occurred despite the daily oral intake of AL extract.

  19. Cardiac surgery-associated acute kidney injury

    PubMed Central

    Ortega-Loubon, Christian; Fernández-Molina, Manuel; Carrascal-Hinojal, Yolanda; Fulquet-Carreras, Enrique

    2016-01-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-recognized complication resulting with the higher morbid-mortality after cardiac surgery. In its most severe form, it increases the odds ratio of operative mortality 3–8-fold, length of stay in the Intensive Care Unit and hospital, and costs of care. Early diagnosis is critical for an optimal treatment of this complication. Just as the identification and correction of preoperative risk factors, the use of prophylactic measures during and after surgery to optimize renal function is essential to improve postoperative morbidity and mortality of these patients. Cardiopulmonary bypass produces an increased in tubular damage markers. Their measurement may be the most sensitive means of early detection of AKI because serum creatinine changes occur 48 h to 7 days after the original insult. Tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 are most promising as an early diagnostic tool. However, the ideal noninvasive, specific, sensitive, reproducible biomarker for the detection of AKI within 24 h is still not found. This article provides a review of the different perspectives of the CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment. We searched the electronic databases, MEDLINE, PubMed, EMBASE using search terms relevant including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment, in order to provide an exhaustive review of the different perspectives of the CSA-AKI. PMID:27716701

  20. Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia.

    PubMed

    Lafuente, Hector; Pazos, Maria R; Alvarez, Antonia; Mohammed, Nagat; Santos, Martín; Arizti, Maialen; Alvarez, Francisco J; Martinez-Orgado, Jose A

    2016-01-01

    Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult.

  1. Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia

    PubMed Central

    Lafuente, Hector; Pazos, Maria R.; Alvarez, Antonia; Mohammed, Nagat; Santos, Martín; Arizti, Maialen; Alvarez, Francisco J.; Martinez-Orgado, Jose A.

    2016-01-01

    Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult. PMID:27462203

  2. Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation.

    PubMed

    Ishibashi, Y; Matsui, T; Yamagishi, S

    2016-03-01

    Ninety percent of glucose filtered by the glomerulus is reabsorbed by a sodium-glucose cotransporter 2 (SGLT2), which is mainly expressed on S1 and S2 segment of renal proximal tubules. Since SGLT-2-mediated glucose reabsorption is increased under diabetic conditions, selective inhibition of SGLT2 is a potential therapeutic target for the treatment of diabetes. We have recently shown that an inhibitor of SGLT2 has anti-inflammatory and antifibrotic effects on experimental diabetic nephropathy partly by suppressing advanced glycation end products formation and oxidative stress generation in the kidney. However, the direct effects of SGLT2 inhibitor on tubular cell damage remain unclear. In this study, we investigated the effects of tofogliflozin, a highly selective inhibitor of SGLT2 on oxidative stress generation, inflammatory and proapoptotic reactions in cultured human proximal tubular cells exposed to high glucose. Tofogliflozin dose-dependently suppressed glucose entry into tubular cells. High glucose exposure (30 mM) for 4 and 24 h significantly increased oxidative stress generation in tubular cells, which were suppressed by the treatment of tofogliflozin or an antioxidant N-acetylcysteine (NAC). Monocyte chemoattractant protein-1 (MCP-1) gene expression and apoptotic cell death were induced by 4 h- and 8 day-exposure to high glucose, respectively, both of which were also blocked by tofogliflozin or NAC. The present study suggests that SGLT2-mediated glucose entry into tubular cells could stimulate oxidative stress and evoke inflammatory and proapoptotic reactions in this cell type. Blockade of glucose reabsorption in tubular cells by SGLT2 inhibitor might exert beneficial effects on tubulointerstitial damage in diabetic nephropathy.

  3. Signaling through the interleukin-18 receptor α attenuates inflammation in cisplatin-induced acute kidney injury.

    PubMed

    Nozaki, Yuji; Kinoshita, Koji; Yano, Tomohiro; Asato, Kayo; Shiga, Toshihiko; Hino, Shoichi; Niki, Kaoru; Nagare, Yasuaki; Kishimoto, Kazuya; Shimazu, Hideki; Funauchi, Masanori; Matsumura, Itaru

    2012-10-01

    Interleukin (IL)-18 is produced by leukocytes and renal parenchymal cells (tubular epithelial cells, podocytes, and mesangial cells). The IL-18 receptor (IL-18R) is expressed on these cells in cisplatin-induced acute kidney injury, but the role of IL-18R is unknown. To help define this, we compared IL-18Rα knockout with wild-type mice in cisplatin-induced acute kidney injury and found deteriorated kidney function, tubular damage, increased accumulation of leukocytes (CD4(+) and CD8(+) T-cells, macrophages, and neutrophils), upregulation of early kidney injury biomarkers (serum TNF, urinary IL-18, and KIM-1 levels), and increased expression of pro-inflammatory molecules downstream of IL-18. In vitro, leukocytes from the spleen and kidneys of the knockout mice produced greater amounts of pro-inflammatory cytokines upon stimulation with concanavalin A compared to that in wild-type mice. Levels of the suppressor of cytokine signaling 1 and 3 (negative regulators of cytokine signaling) were reduced in the spleen and kidneys of IL-18Rα-deficient compared to wild-type mice. Adoptive transfer of wild-type splenocytes by IL-18Rα-deficient mice led to decreased cisplatin nephrotoxicity compared to control IL-18Rα-deficient mice. In contrast, anti-IL-18Rα and anti-IL-18Rβ antibody treatment tended to increase cisplatin nephrotoxicity in wild-type mice. Thus, signaling through IL-18Rα activates both inflammation-suppressing and pro-injury pathways in cisplatin-induced acute kidney injury.

  4. Deferasirox-induced iron depletion promotes BclxL downregulation and death of proximal tubular cells.

    PubMed

    Martin-Sanchez, Diego; Gallegos-Villalobos, Angel; Fontecha-Barriuso, Miguel; Carrasco, Susana; Sanchez-Niño, Maria Dolores; Lopez-Hernandez, Francisco J; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belén

    2017-01-31

    Iron deficiency has been associated with kidney injury. Deferasirox is an oral iron chelator used to treat blood transfusion-related iron overload. Nephrotoxicity is the most serious and common adverse effect of deferasirox and may present as an acute or chronic kidney disease. However, scarce data are available on the molecular mechanisms of nephrotoxicity. We explored the therapeutic modulation of deferasirox-induced proximal tubular cell death in culture. Deferasirox induced dose-dependent tubular cell death and AnexxinV/7AAD staining showed features of apoptosis and necrosis. However, despite inhibiting caspase-3 activation, the pan-caspase inhibitor zVAD-fmk failed to prevent deferasirox-induced cell death. Moreover, zVAD increased deferasirox-induced cell death, a feature sometimes found in necroptosis. Electron microscopy identified mitochondrial injury and features of necrosis. However, neither necrostatin-1 nor RIP3 knockdown prevented deferasirox-induced cell death. Deferasirox caused BclxL depletion and BclxL overexpression was protective. Preventing iron depletion protected from BclxL downregulation and deferasirox cytotoxicity. In conclusion, deferasirox promoted iron depletion-dependent cell death characterized by BclxL downregulation. BclxL overexpression was protective, suggesting a role for BclxL downregulation in iron depletion-induced cell death. This information may be used to develop novel nephroprotective strategies. Furthermore, it supports the concept that monitoring kidney tissue iron depletion may decrease the risk of deferasirox nephrotoxicity.

  5. Deferasirox-induced iron depletion promotes BclxL downregulation and death of proximal tubular cells

    PubMed Central

    Martin-Sanchez, Diego; Gallegos-Villalobos, Angel; Fontecha-Barriuso, Miguel; Carrasco, Susana; Sanchez-Niño, Maria Dolores; Lopez-Hernandez, Francisco J; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belén

    2017-01-01

    Iron deficiency has been associated with kidney injury. Deferasirox is an oral iron chelator used to treat blood transfusion-related iron overload. Nephrotoxicity is the most serious and common adverse effect of deferasirox and may present as an acute or chronic kidney disease. However, scarce data are available on the molecular mechanisms of nephrotoxicity. We explored the therapeutic modulation of deferasirox-induced proximal tubular cell death in culture. Deferasirox induced dose-dependent tubular cell death and AnexxinV/7AAD staining showed features of apoptosis and necrosis. However, despite inhibiting caspase-3 activation, the pan-caspase inhibitor zVAD-fmk failed to prevent deferasirox-induced cell death. Moreover, zVAD increased deferasirox-induced cell death, a feature sometimes found in necroptosis. Electron microscopy identified mitochondrial injury and features of necrosis. However, neither necrostatin-1 nor RIP3 knockdown prevented deferasirox-induced cell death. Deferasirox caused BclxL depletion and BclxL overexpression was protective. Preventing iron depletion protected from BclxL downregulation and deferasirox cytotoxicity. In conclusion, deferasirox promoted iron depletion-dependent cell death characterized by BclxL downregulation. BclxL overexpression was protective, suggesting a role for BclxL downregulation in iron depletion-induced cell death. This information may be used to develop novel nephroprotective strategies. Furthermore, it supports the concept that monitoring kidney tissue iron depletion may decrease the risk of deferasirox nephrotoxicity. PMID:28139717

  6. Neural not tubular dopamine increases glomerular filtration rate in perfused rat kidneys.

    PubMed

    Baines, A D; Drangova, R

    1986-04-01

    We examined the effect of endogenous neural and tubular dopamine production on renal function in isolated perfused kidneys. Nerves and proximal tubules in perfused kidneys produce dopamine from endogenous substrates. Surgical denervation 5-14 days before perfusion removed neural dopamine production and decreased dopamine excretion 32% (P less than 0.05), inulin clearance 7% (P less than 0.05), and sodium excretion 57% (P less than 0.01). Carbidopa, which abolished neural and tubular dopamine production, produced similar functional effects. Haloperidol, Sch 23390, and (+)butaclamol, but not (-)butaclamol, added during perfusion increased renovascular resistance 4-5% (P less than 0.001) and decreased inulin clearance 20% (P less than 0.001). Sch 23390 reduced fractional sodium excretion (P less than 0.01), but haloperidol and butaclamol did not. Chronic denervation or carbidopa blocked the reduction of inulin clearance by haloperidol, but alpha- and beta-adrenergic antagonists did not. Fractional sodium excretion increased after adding haloperidol to denervated or adrenergic blocked kidneys. Denervation blocked the effect of Sch 23390 on inulin clearance but not on sodium excretion. Haloperidol inhibited dopamine excretion. Thus dopamine released from acutely severed nerves in perfused kidneys increases glomerular filtration rate (GFR). Dopamine produced by tubules of chronically denervated kidneys did not influence GFR but stimulated sodium excretion by an Sch 23390-sensitive mechanism.

  7. Generation of kidney tubular organoids from human pluripotent stem cells

    PubMed Central

    Yamaguchi, Shintaro; Morizane, Ryuji; Homma, Koichiro; Monkawa, Toshiaki; Suzuki, Sayuri; Fujii, Shizuka; Koda, Muneaki; Hiratsuka, Ken; Yamashita, Maho; Yoshida, Tadashi; Wakino, Shu; Hayashi, Koichi; Sasaki, Junichi; Hori, Shingo; Itoh, Hiroshi

    2016-01-01

    Recent advances in stem cell research have resulted in methods to generate kidney organoids from human pluripotent stem cells (hPSCs), which contain cells of multiple lineages including nephron epithelial cells. Methods to purify specific types of cells from differentiated hPSCs, however, have not been established well. For bioengineering, cell transplantation, and disease modeling, it would be useful to establish those methods to obtain pure populations of specific types of kidney cells. Here, we report a simple two-step differentiation protocol to generate kidney tubular organoids from hPSCs with direct purification of KSP (kidney specific protein)-positive cells using anti-KSP antibody. We first differentiated hPSCs into mesoderm cells using a glycogen synthase kinase-3β inhibitor for 3 days, then cultured cells in renal epithelial growth medium to induce KSP+ cells. We purified KSP+ cells using flow cytometry with anti-KSP antibody, which exhibited characteristics of all segments of kidney tubular cells and cultured KSP+ cells in 3D Matrigel, which formed tubular organoids in vitro. The formation of tubular organoids by KSP+ cells induced the acquisition of functional kidney tubules. KSP+ cells also allowed for the generation of chimeric kidney cultures in which human cells self-assembled into 3D tubular structures in combination with mouse embryonic kidney cells. PMID:27982115

  8. Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats.

    PubMed

    Leite, Aline de Lima; Santiago, Joel Ferreira; Levy, Flavia Mauad; Maria, Andrea Gutierrez; Fernandes, Mileni da Silva; Salvadori, Daisy Maria Favero; Ribeiro, Daniel Araki; Buzalaf, Marilia Afonso Rabelo

    2007-05-01

    Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure.

  9. Kidney Injury Molecule-1 Protects against Gα12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury

    PubMed Central

    Ismail, Ola Z.; Zhang, Xizhong; Wei, Junjun; Haig, Aaron; Denker, Bradley M.; Suri, Rita S.; Sener, Alp; Gunaratnam, Lakshman

    2016-01-01

    Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein α12 (Gα12) subunit by reactive oxygen species is a major cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated during acute kidney injury, but the physiologic significance of this up-regulation is unclear. Here, we report for the first time that Kim-1 inhibits Gα12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Gα12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Gα12. Compared with Kim-1+/+ mice, Kim-1−/− mice exhibited greater Gα12 and downstream Src activation both in primary tubular epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after unilateral renal artery clamping. Finally, we show that Kim-1–deficient mice had more severe kidney dysfunction and tissue damage after bilateral renal artery clamping, compared with wild-type mice. Our results suggest that KIM-1 is an endogenous protective mechanism against renal ischemia-reperfusion injury through inhibition of Gα12. PMID:25759266

  10. The yin and yang of autophagy in acute kidney injury.

    PubMed

    Melk, Anette; Baisantry, Arpita; Schmitt, Roland

    2016-01-01

    Antagonizing the strongly activated pathway of autophagy in renal ischemic injury has been associated with poor outcome. In our recent study we used mice with a selective deletion of Atg5 in the S3 proximal tubule segment, which is most susceptible to ischemic damage. In line with the notion that autophagy is a prosurvival mechanism our studies revealed an early accelerated cell death of heavily damaged tubular cells in the S3 segment of these mice. Interestingly, this expedited loss of cells was associated with better long-term outcome as reflected by less inflammation, improved tubular repair, and function and reduced accumulation of senescent cells. While these data confirm the role of tubular autophagy as a prosurvival mechanism in ischemic kidney injury, they also show that autophagy may enable severely damaged cells to persist and exert deleterious effects. Such ambivalent effects might be of relevance if modulating autophagy is considered as a therapeutic option.

  11. The yin and yang of autophagy in acute kidney injury

    PubMed Central

    Melk, Anette; Baisantry, Arpita; Schmitt, Roland

    2016-01-01

    ABSTRACT Antagonizing the strongly activated pathway of autophagy in renal ischemic injury has been associated with poor outcome. In our recent study we used mice with a selective deletion of Atg5 in the S3 proximal tubule segment, which is most susceptible to ischemic damage. In line with the notion that autophagy is a prosurvival mechanism our studies revealed an early accelerated cell death of heavily damaged tubular cells in the S3 segment of these mice. Interestingly, this expedited loss of cells was associated with better long-term outcome as reflected by less inflammation, improved tubular repair, and function and reduced accumulation of senescent cells. While these data confirm the role of tubular autophagy as a prosurvival mechanism in ischemic kidney injury, they also show that autophagy may enable severely damaged cells to persist and exert deleterious effects. Such ambivalent effects might be of relevance if modulating autophagy is considered as a therapeutic option. PMID:26761120

  12. p66Shc: A novel biomarker of tubular oxidative injury in patients with diabetic nephropathy

    PubMed Central

    Xu, Xiaoxuan; Zhu, Xuejing; Ma, Mingming; Han, Yachun; Hu, Chun; Yuan, Shuguang; Yang, Yuan; Xiao, Li; Liu, Fuyou; Kanwar, Yashpal S.; Sun, Lin

    2016-01-01

    Increased p66Shc expression has been associated with diabetic nephropathy (DN). However, whether p66Shc can serve as a potential biomarker for tubular oxidative injury in DN is unknown. We measured the expression of p66Shc in peripheral blood monocytes (PBMs) and renal biopsy tissues from DN patients and then analysed the relationship between p66Shc expression and the clinical characteristics of patients with DN. Patients were divided into 4 groups (class IIa, class IIb, class III and the control group). qPCR, Western blotting and immunohistochemistry were performed. The results showed that both p66Shc and p-p66Shc expression significantly increased in PBMs and kidney tissues of DN patients. Moreover, Spearman’s correlation and multiple regression analyses were carried out. A positive relationship between the p66Shc expression and oxidative stress was found. p66Shc and oxidative stress were significant predictors of the degree of tubular damage. In addition, p66Shc expression was positively correlated with the concentrations of β-NAG, UACR and 8-OHdG, low-density lipoprotein and blood glucose levels, and duration of diabetes in patients with DN from class IIa to class III. These data indicated that increased expression of p66Shc may serve as a therapeutic target and a novel biomarker of DN. PMID:27377870

  13. Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface

    PubMed Central

    Tian, Hong-Chang; Liu, Jing-Quan; Kang, Xiao-Yang; Tang, Long-Jun; Wang, Ming-Hao; Ji, Bo-Wen; Yang, Bin; Wang, Xiao-Lin; Chen, Xiang; Yang, Chun-Sheng

    2016-01-01

    Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification. PMID:27229174

  14. Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface

    NASA Astrophysics Data System (ADS)

    Tian, Hong-Chang; Liu, Jing-Quan; Kang, Xiao-Yang; Tang, Long-Jun; Wang, Ming-Hao; Ji, Bo-Wen; Yang, Bin; Wang, Xiao-Lin; Chen, Xiang; Yang, Chun-Sheng

    2016-05-01

    Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification.

  15. 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}.

  16. Open-closed switching of synthetic tubular pores

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

  17. 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

  18. 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.

  19. 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.

  20. Extremely strong tubular stacking of aromatic oligoamide macrocycles

    DOE PAGES

    Kline, Mark A.; Wei, Xiaoxi; Horner, Ian J.; ...

    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

  1. Numerical study of cavitation flows inside a tubular pumping station

    NASA Astrophysics Data System (ADS)

    Tang, X. L.; Huang, W.; Wang, F. J.; Yang, W.; Wu, Y. L.

    2012-11-01

    Based on RNG k-epsilon turbulence model and the full cavitation model, the cavitation flows inside a low-head tubular-pump model were predicted by using the FLUENT software. For a operating case of given flow rate, cavitation happens near the inlet on the suction surfaces of the impeller blades at the initial cavitating stage, and the cavitating area spreads to the impeller passage and hub as NPSH (net positive suction head) decreases, which will affect energy transformation. For various operating cases of cavitation flows at the given flow rates, the predicted velocity and pressure distributions as well as the vapor volumetric fraction are systematically analyzed. Finally, the cavitation performance curve of the tubular-pump model is obtained by means of the further post-processing. All the comparisons and analysis can be further employed to optimize the hydraulic and structural design of the tubular pump and to guide its safe operation.

  2. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    SciTech Connect

    Cárdenas-González, Mariana C.; Del Razo, Luz M.; Barrera-Chimal, Jonatan; Jacobo-Estrada, Tania; López-Bayghen, Esther; and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  3. Effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats

    PubMed Central

    PENG, TAO; WANG, JIE; ZHEN, JUNHUI; HU, ZHAO; YANG, XIANGDONG

    2014-01-01

    The aim of this study was to investigate the effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats. Thirty male Sprague-Dawley rats were included in the present study. Eight of the 30 rats were randomly selected and served as the normal control group (N group), while the remaining 22 rats, injected with streptozotocin (STZ), comprised the diabetic rat model. Rats with diabetes were randomly divided into the diabetic (DM group) and benazepril (B group) groups. The total course was conducted over 12 weeks. Blood glucose, body weight, kidney/body weight, 24-h urinary protein, serum creatinine and blood urea nitrogen were measured at the start and end of the study. We observed the tubulointerstitial pathological changes, and applied immunohistochemistry and western blotting to detect the expression of α-smooth muscle actin (α-SMA) in renal tissue. The levels of blood glucose, kidney/body weight, 24-h urinary protein, serum creatinine, blood urea nitrogen and tubulointerstitial damage index (TII) in the DM group were significantly higher than that in the N group (p<0.01). Except for blood glucose and kidney/body weight, the remaining indices were lower in the B group compared with those in the DM group (p<0.01). Immunohistochemical staining results revealed the expression of α-SMA in renal tubular epithelial cells to be significantly higher in the DM and B groups compared with the control (N) group (p<0.01). Western blot analysis revealed that the expression of α-SMA in diabetic renal tissue increased 3.27-fold compared with that of the N group, while the expression of α-SMA in the B group decreased 45% compared with that in the DM group. In conclusion, benazepril significantly reduced the expression of α-SMA in renal tubular epithelial cells obtained from diabetic rats, inhibited the transdifferentiation of renal tubular epithelial cells and played an important role in kidney protection. PMID:24944793

  4. Gain of cellular adaptation due to prolonged p53 impairment leads to functional switchover from p53 to p73 during DNA damage in acute myeloid leukemia cells.

    PubMed

    Chakraborty, Juni; Banerjee, Shuvomoy; Ray, Pallab; Hossain, Dewan Md Sakib; Bhattacharyya, Sankar; Adhikary, Arghya; Chattopadhyay, Sreya; Das, Tanya; Sa, Gaurisankar

    2010-10-22

    Tumor suppressor p53 plays the central role in regulating apoptosis in response to genotoxic stress. From an evolutionary perspective, the activity of p53 has to be backed up by other protein(s) in case of any functional impairment of this protein, to trigger DNA damage-induced apoptosis in cancer cells. We adopted multiple experimental approaches to demonstrate that in p53-impaired cancer cells, DNA damage caused accumulation of p53 paralogue p73 via Chk-1 that strongly impacted Bax expression and p53-independent apoptosis. On the contrary, when p53 function was restored by ectopic expression, Chk-2 induced p53 accumulation that in turn overshadowed p73 activity, suggesting an antagonistic interaction between p53 family members. To understand such interaction better, p53-expressing cells were impaired differentially for p53 activity. In wild-type p53-expressing cancer cells that were silenced for p53 for several generations, p73 was activated, whereas no such trend was observed when p53 was transiently silenced. Prolonged p53 interference, even in functional p53 settings, therefore, leads to the "gain of cellular adaptation" in a way that alters the cellular microenvironment in favor of p73 activation by altering p73-regulatory proteins, e.g. Chk1 activation and dominant negative p73 down-regulation. These findings not only unveil a hitherto unexplained mechanism underlying the functional switchover from p53 to p73, but also validate p73 as a promising and potential target for cancer therapy in the absence of functional p53.

  5. Strength of Welded Joints in Tubular Members for Aircraft

    DTIC Science & Technology

    1930-02-06

    STRENGTH OF WELDED JOINTS IN TUBULAR MEMBERS FOR AIRCRAFT By H. L. WHITTEMORE and W. C. BRUEGGEMAN Bureau of Standards ——— - ..— .-.— .— .— —___ 107346->1...331 331 332 341 341 342 343 343 343 347 347 347 367 .— .— — ● REPORT ~0, 348 STRENGTH OF WELDED JOINTS IN TUBULAR MELMBERS FOR AIRCRAFT By H. L...airoraft welds has been publi~hed)lit ig beh%redthat euch tests made by a disinterested governmental laboratory should be of considerablemdueto the

  6. In vivo and in vitro 31P magnetic resonance spectroscopic studies of the hepatic response of healthy rats and rats with acute hepatic damage to fructose loading.

    PubMed

    Lu, W; Locke, S J; Brauer, M

    1994-05-01

    The hepatic response to a fructose challenge for control rats, and rats subjected to an acute sublethal dose of carbon tetrachloride (CCl4) or bromobenzene (BB), was compared using dynamic in vivo 31P MRS. Fructose loading conditions were used in which control rats showed only a modest increase in hepatic phosphomonoester (PME), and a small decrease in ATP, Pi, and intracellular pH after fructose administration. Both CCl4 and BB-treated rats showed a much greater fructose-induced accumulation of PME than did controls. Trolox C, a free radical scavenger, prevented most of this PME increase. BB-treated rats, given sufficient time to recover from the hepatotoxic insult, responded to the fructose load similarly to controls. Liver aldolase activities of control, toxicant-treated rats, and toxicant plus Trolox C-treated rats correlated inversely with PME accumulation after fructose loading (correlation coefficient: -0.834, P < 0.05). Perchloric acid extracts of rat livers studied by in vitro 31P MRS confirmed that the PME accumulation after fructose loading is mainly due to an increase in fructose 1-phosphate. These studies are consistent with the aldolase-catalyzed cleavage of fructose 1-phosphate being rate-limiting in hepatic fructose metabolism, and that the CCl4 and BB treatment modify and inactivate the aldolase enzyme.

  7. An experimental investigation of fatigue-crack growth in drillstring tubulars

    SciTech Connect

    Dale, B.A.

    1988-12-01

    Drillstring failures continue to plague the oil industry, often costing millions of dollars each year. This problem is frequently intensified with the drilling of deep, deviated wellbores or ''hard rock'' drilling conditions. The drilling industry attempts to guard against these costly failures by performing periodic nondestructive inspections to remove damaged tubulars from service. This paper describes the results of full-scale fatigue-crack-growth tests of drill collars under rotating and bending loads. In addition, corrosion fatigue-crack-growth data are also presented for API drillpipe steels in air and in three representative water-based drilling-fluid environments. Based on this experimental investigation, the test data support the practical application of fatigue-crack-growth mechanics principles for the development of nondestructive inspection intervals to reduce drillstring failures.

  8. 75 FR 3248 - Certain Oil Country Tubular Goods From China

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... COMMISSION Certain Oil Country Tubular Goods From China Determination On the basis of the record \\1... industry in the United States is threatened with material injury by reason of imports from China of certain... Commerce ] (Commerce) to be subsidized by the Government of China. 2 3 \\1\\ The record is defined in...

  9. Nonlinear Analysis of Bonded Composite Tubular Lap Joints

    NASA Technical Reports Server (NTRS)

    Oterkus, E.; Madenci, E.; Smeltzer, S. S., III; Ambur, D. R.

    2005-01-01

    The present study describes a semi-analytical solution method for predicting the geometrically nonlinear response of a bonded composite tubular single-lap joint subjected to general loading conditions. The transverse shear and normal stresses in the adhesive as well as membrane stress resultants and bending moments in the adherends are determined using this method. The method utilizes the principle of virtual work in conjunction with nonlinear thin-shell theory to model the adherends and a cylindrical shear lag model to represent the kinematics of the thin adhesive layer between the adherends. The kinematic boundary conditions are imposed by employing the Lagrange multiplier method. In the solution procedure, the displacement components for the tubular joint are approximated in terms of non-periodic and periodic B-Spline functions in the longitudinal and circumferential directions, respectively. The approach presented herein represents a rapid-solution alternative to the finite element method. The solution method was validated by comparison against a previously considered tubular single-lap joint. The steep variation of both peeling and shearing stresses near the adhesive edges was successfully captured. The applicability of the present method was also demonstrated by considering tubular bonded lap-joints subjected to pure bending and torsion.

  10. Osteomalacia associated with increased renal tubular resorption of phosphate (hypohyperparathyroidism)

    PubMed Central

    Kanis, J. A.; Walton, R. J.

    1976-01-01

    A 12-year-old girl, who presented with joint pains, was found to have hypocalcaemia, hyperphosphataemia due to increased renal tubular reabsorption, increased serum alkaline phosphatase activity, and osteomalacia. These features, which resemble those found in so-called hypohyperparathyroidism, were all rapidly reversed by small doses of cholecalciferol. PMID:183195

  11. Renal pathophysiologic role of cortical tubular inclusion bodies.

    PubMed

    Radi, Zaher A; Stewart, Zachary S; Grzemski, Felicity A; Bobrowski, Walter F

    2013-01-01

    Renal tubular inclusion bodies are rarely associated with drug administration. The authors describe the finding of renal cortical tubular intranuclear and intracytoplasmic inclusion bodies associated with the oral administration of a norepinephrine/serotonin reuptake inhibitor (NSRI) test article in Sprague-Dawley (SD) rats. Rats were given an NSRI daily for 4 weeks, and kidney histopathologic, ultrastructural pathology, and immunohistochemical examinations were performed. Round eosinophilic intranuclear inclusion bodies were observed histologically in the tubular epithelial cells of the renal cortex in male and female SD rats given the NSRI compound. No evidence of degeneration or necrosis was noted in the inclusion-containing renal cells. By ultrastructural pathology, inclusion bodies consisted of finely granular, amorphous, and uniformly stained nonmembrane-bound material. By immunohistochemistry, inclusion bodies stained positive for d-amino acid oxidase (DAO) protein. In addition, similar inclusion bodies were noted in the cytoplasmic tubular epithelial compartment by ultrastructural and immunohistochemical examination.  This is the first description of these renal inclusion bodies after an NSRI test article administration in SD rats. Such drug-induced renal inclusion bodies are rat-specific, do not represent an expression of nephrotoxicity, represent altered metabolism of d-amino acids, and are not relevant to human safety risk assessment.

  12. Tubular Surface Segmentation for Extracting Anatomical Structures From Medical Imagery

    PubMed Central

    Sundaramoorthi, Ganesh; Tannenbaum, Allen

    2011-01-01

    This work provides a model for tubular structures, and devises an algorithm to automatically extract tubular anatomical structures from medical imagery. Our model fits many anatomical structures in medical imagery, in particular, various fiber bundles in the brain (imaged through diffusion-weighted magnetic resonance (DW-MRI)) such as the cingulum bundle, and blood vessel trees in computed tomography angiograms (CTAs). Extraction of the cingulum bundle is of interest because of possible ties to schizophrenia, and extracting blood vessels is helpful in the diagnosis of cardiovascular diseases. The tubular model we propose has advantages over many existing approaches in literature: fewer degrees-of-freedom over a general deformable surface hence energies defined on such tubes are less sensitive to undesirable local minima, and the tube (in 3-D) can be naturally represented by a 4-D curve (a radius function and centerline), which leads to computationally less costly algorithms and has the advantage that the centerline of the tube is obtained without additional effort. Our model also generalizes to tubular trees, and the extraction algorithm that we design automatically detects and evolves branches of the tree. We demonstrate the performance of our algorithm on 20 datasets of DW-MRI data and 32 datasets of CTA, and quantify the results of our algorithm when expert segmentations are available. PMID:21118754

  13. Molecular tectonics: tubular crystals with controllable channel size and orientation.

    PubMed

    Lin, Mei-Jin; Jouaiti, Abdelaziz; Pocic, David; Kyritsakas, Nathalie; Planeix, Jean-Marc; Hosseini, Mir Wais

    2010-01-07

    The combination of flexible neutral organic tectons based on two pyridines interconnected by a thioether or thioester type spacer with an inorganic ZnSiF(6) pillar leads to the formation of 2-D coordination networks and the packing of the latter generates crystals offering controllable tubular channels with imposed orientation along the pillar axis.

  14. Hollow tubular porous covalent organic framework (COF) nanostructures.

    PubMed

    Pachfule, Pradip; Kandmabeth, Sharath; Mallick, Arijit; Banerjee, Rahul

    2015-07-25

    Hollow and tubular TpPa-COF structures have been synthesized by template-assisted replication of nanometer sized ZnO-nanorods. The hollow structures composed of microporous TpPa shells have high periodicity, moderate porosity, chemical stability and capsule shaped morphology as revealed by X-ray diffraction, porosity measurements, and SEM and TEM analyses.

  15. Cystinosis (ctns) zebrafish mutant shows pronephric glomerular and tubular dysfunction

    PubMed Central

    Elmonem, Mohamed A.; Khalil, Ramzi; Khodaparast, Ladan; Khodaparast, Laleh; Arcolino, Fanny O.; Morgan, Joseph; Pastore, Anna; Tylzanowski, Przemko; Ny, Annelii; Lowe, Martin; de Witte, Peter A.; Baelde, Hans J.; van den Heuvel, Lambertus P.; Levtchenko, Elena

    2017-01-01

    The human ubiquitous protein cystinosin is responsible for transporting the disulphide amino acid cystine from the lysosomal compartment into the cytosol. In humans, Pathogenic mutations of CTNS lead to defective cystinosin function, intralysosomal cystine accumulation and the development of cystinosis. Kidneys are initially affected with generalized proximal tubular dysfunction (renal Fanconi syndrome), then the disease rapidly affects glomeruli and progresses towards end stage renal failure and multiple organ dysfunction. Animal models of cystinosis are limited, with only a Ctns knockout mouse reported, showing cystine accumulation and late signs of tubular dysfunction but lacking the glomerular phenotype. We established and characterized a mutant zebrafish model with a homozygous nonsense mutation (c.706 C > T; p.Q236X) in exon 8 of ctns. Cystinotic mutant larvae showed cystine accumulation, delayed development, and signs of pronephric glomerular and tubular dysfunction mimicking the early phenotype of human cystinotic patients. Furthermore, cystinotic larvae showed a significantly increased rate of apoptosis that could be ameliorated with cysteamine, the human cystine depleting therapy. Our data demonstrate that, ctns gene is essential for zebrafish pronephric podocyte and proximal tubular function and that the ctns-mutant can be used for studying the disease pathogenic mechanisms and for testing novel therapies for cystinosis. PMID:28198397

  16. Tubular surface segmentation for extracting anatomical structures from medical imagery.

    PubMed

    Mohan, Vandana; Sundaramoorthi, Ganesh; Tannenbaum, Allen

    2010-12-01

    This work provides a model for tubular structures, and devises an algorithm to automatically extract tubular anatomical structures from medical imagery. Our model fits many anatomical structures in medical imagery, in particular, various fiber bundles in the brain (imaged through diffusion-weighted magnetic resonance (DW-MRI)) such as the cingulum bundle, and blood vessel trees in computed tomography angiograms (CTAs). Extraction of the cingulum bundle is of interest because of possible ties to schizophrenia, and extracting blood vessels is helpful in the diagnosis of cardiovascular diseases. The tubular model we propose has advantages over many existing approaches in literature: fewer degrees-of-freedom over a general deformable surface hence energies defined on such tubes are less sensitive to undesirable local minima, and the tube (in 3-D) can be naturally represented by a 4-D curve (a radius function and centerline), which leads to computationally less costly algorithms and has the advantage that the centerline of the tube is obtained without additional effort. Our model also generalizes to tubular trees, and the extraction algorithm that we design automatically detects and evolves branches of the tree. We demonstrate the performance of our algorithm on 20 datasets of DW-MRI data and 32 datasets of CTA, and quantify the results of our algorithm when expert segmentations are available.

  17. Double breasting spongioplasty in tubularized/tubularized incise plate urethroplasty: A new technique

    PubMed Central

    Bhat, Amilal; Bhat, Mahakshit; Kumar, Rajeev; Bhat, Akshita

    2017-01-01

    Introduction: The main disadvantage of currently described techniques of spongioplasty is superimposition of 3 suture lines (neourethra, spongioplasty, and skin closure) which is likely to increase the chances of a fistula. We describe and evaluate the results of a double breasting spongioplasty in urethroplasty. Methods: A prospective study of 60 primary hypospadias was undertaken by double breasting spongioplasty from August 2012 to March 2014. Mobilization of the urethral plate and the spongiosum is done by creating a plane just proximal to the meatus. Double breasting spongioplasty is done after tubularization of urethral plate. First layer of spongiosum is sutured toward lateral side of the neourethra covering the suture line. A second double breasting layer is sutured over the first layer with its suture line toward the opposite side covering the suture line of the first layer; thus avoiding overlapping of suture lines of all the three layers. Results: Age of the patients varied from 10 months to 16 years with a mean and median of 3.73 and 3.50 years, respectively. Hypospadias was distal, mid, and proximal in 38, 10, and 12 cases, respectively. Chordee was noticed in 35 cases and torque in 28 cases. Overall complication rate was 5% and fistula rate was 1.66%. Conclusions: Double breasting spongioplasty avoids superimposition of suture line and adds two layers of spongiosum over neourethra, thus decreases the chances of urethral fistula and gives cylindrical shape to neourethra. PMID:28197032

  18. Mouse model of human RPE65 P25L hypomorph resembles wild type under normal light rearing but is fully resistant to acute light damage

    PubMed Central

    Li, Yan; Yu, Shirley; Duncan, Todd; Li, Yichao; Liu, Pinghu; Gene, Erelda; Cortes-Pena, Yoel; Qian, Haohua; Dong, Lijin; Redmond, T. Michael

    2015-01-01

    Human RPE65 mutations cause a spectrum of blinding retinal dystrophies from severe early-onset disease to milder manifestations. The RPE65 P25L missense mutation, though having <10% of wild-type (WT) activity, causes relatively mild retinal degeneration. To better understand these mild forms of RPE65-related retinal degeneration, and their effect on cone photoreceptor survival, we generated an Rpe65/P25L knock-in (KI/KI) mouse model. We found that, when subject to the low-light regime (∼100 lux) of regular mouse housing, homozygous Rpe65/P25L KI/KI mice are morphologically and functionally very similar to WT siblings. While mutant protein expression is decreased by over 80%, KI/KI mice retinae retain comparable 11-cis-retinal levels with WT. Consistently, the scotopic and photopic electroretinographic (ERG) responses to single-flash stimuli also show no difference between KI/KI and WT mice. However, the recovery of a-wave response following moderate visual pigment bleach is delayed in KI/KI mice. Importantly, KI/KI mice show significantly increased resistance to high-intensity (20 000 lux for 30 min) light-induced retinal damage (LIRD) as compared with WT, indicating impaired rhodopsin regeneration in KI/KI. Taken together, the Rpe65/P25L mutant produces sufficient chromophore under normal conditions to keep opsins replete and thus manifests a minimal phenotype. Only when exposed to intensive light is this hypomorphic mutation manifested physiologically, as its reduced expression and catalytic activity protects against the successive cycles of opsin regeneration underlying LIRD. These data also help define minimal requirements of chromophore for photoreceptor survival in vivo and may be useful in assessing a beneficial therapeutic dose for RPE65 gene therapy in humans. PMID:25972377

  19. Geochemical characterization of tubular alteration features in subseafloor basalt glass

    NASA Astrophysics Data System (ADS)

    Knowles, Emily; Staudigel, Hubert; Templeton, Alexis

    2013-07-01

    There are numerous indications that subseafloor basalts may currently host a huge quantity of active microbial cells and contain biosignatures of ancient life in the form of physical and chemical basalt glass alteration. Unfortunately, technological challenges prevent us from observing the formation and mineralization of these alteration features in situ, or reproducing tubular basalt alteration processes in the laboratory. Therefore, comprehensive analysis of the physical and chemical traces retained in mineralized tubules is currently the best approach for deciphering a record of glass alteration. We have used a number of high-resolution spectroscopic and microscopic methods to probe the geochemical and mineralogical characteristics of tubular alteration features in basalt glasses obtained from a suite of subseafloor drill cores that covers a range of different collection locations and ages. By combining three different synchrotron-based X-ray measurements - X-ray fluorescence microprobe mapping, XANES spectroscopy, and μ-XRD - with focused ion beam milling and transmission electron microscopy, we have spatially resolved the major and trace element distributions, as well as the oxidation state of Fe, determined the coordination chemistry of Fe, Mn and Ti at the micron-scale, and constrained the secondary minerals within these features. The tubular alteration features are characterized by strong losses of Fe2+, Mn2+, and Ca2+ compared to fresh glass, oxidation of the residual Fe, and the accumulation of Ti and Cu. The predominant phases infilling the alteration regions are Fe3+-bearing silicates dominated by 2:1 clays, with secondary Fe- and Ti-oxides, and a partially oxidized Mn-silicate phase. These geochemical patterns observed within the tubular alteration features are comparable across a diverse suite of samples formed over the past 5-100 Ma, which shows that the microscale mineralization processes are common and consistent throughout the ocean basins and

  20. sup 99m Tc renal tubular function agents: Current status

    SciTech Connect

    Eshima, D.; Fritzberg, A.R.; Taylor, A. Jr. )

    1990-01-01

    Orthoiodohippuric (OIH) acid labeled with 131I is a widely used renal radiopharmaceutical agent and has been the standard radiopharmaceutical agent for the measurement of effective renal plasma flow (EPRF). Limitations to the routine clinical use of 131I OIH are related to the suboptimal imaging properties of the 131I radionuclide and its relatively high radiation dose. 123I has been substituted for 131I; however, its high cost and short shelf-life have limited its widespread use. Recent work has centered on the development of a new 99mTc renal tubular function agent, which would use the optimal radionuclidic properties and availability of 99mTc and combine the clinical information provided by OIH. The search for a suitable 99mTc renal tubular function agent has focused on the diamide dithiolate (N2S2), the paraaminohippuric iminodiacetic acid (PAHIDA), and the triamide mercaptide (N3S) donor ligand systems. To date, the most promising 99mTc tubular function agent is the N3S complex: 99mTc mercaptoacetyltriglycine (99mTc MAG3). Studies in animal models in diuresis, dehydration, acid or base imbalance, ischemia, and renal artery stenosis demonstrate that 99mTc MAG3 behaves similarly to 131I OIH. A simple kit formulation is available that yields the 99mTc MAG3 complex in high radiochemical purity. Studies in normal subjects and patients indicate that 99mTc MAG3 is an excellent 99mTc renal tubular agent, but its plasma clearance is only 50% to 60% that of OIH. In an effort to develop an improved 99mTc renal tubular function agent, changes have been made in the core N3S donor ligand system, but to date no agent has been synthesized that is clinically superior to 99mTc MAG3. 61 references.

  1. Lateral diffusion on tubular membranes: quantification of measurements bias.

    PubMed

    Renner, Marianne; Domanov, Yegor; Sandrin, Fanny; Izeddin, Ignacio; Bassereau, Patricia; Triller, Antoine

    2011-01-01

    Single Particle Tracking (SPT) is a powerful technique for the analysis of the lateral diffusion of the lipid and protein components of biological membranes. In neurons, SPT allows the study of the real-time dynamics of receptors for neurotransmitters that diffuse continuously in and out synapses. In the simplest case where the membrane is flat and is parallel to the focal plane of the microscope the analysis of diffusion from SPT data is relatively straightforward. However, in most biological samples the membranes are curved, which complicates analysis and may lead to erroneous conclusions as for the mode of lateral diffusion. Here we considered the case of lateral diffusion in tubular membranes, such as axons, dendrites or the neck of dendritic spines. Monte Carlo simulations allowed us to evaluate the error in diffusion coefficient (D) calculation if the curvature is not taken into account. The underestimation is determined by the diameter of the tubular surface, the frequency of image acquisition and the degree of mobility itself. We found that projected trajectories give estimates that are 25 to 50% lower than the real D in case of 2D-SPT over the tubular surface. The use of 3D-SPT improved the measurements if the frequency of image acquisition was fast enough in relation to the mobility of the molecules and the diameter of the tube. Nevertheless, the calculation of D from the components of displacements in the axis of the tubular structure gave accurate estimate of D, free of geometrical artefacts. We show the application of this approach to analyze the diffusion of a lipid on model tubular membranes and of a membrane-bound GFP on neurites from cultured rat hippocampal neurons.

  2. Lateral Diffusion on Tubular Membranes: Quantification of Measurements Bias

    PubMed Central

    Sandrin, Fanny; Izeddin, Ignacio; Bassereau, Patricia; Triller, Antoine

    2011-01-01

    Single Particle Tracking (SPT) is a powerful technique for the analysis of the lateral diffusion of the lipid and protein components of biological membranes. In neurons, SPT allows the study of the real-time dynamics of receptors for neurotransmitters that diffuse continuously in and out synapses. In the simplest case where the membrane is flat and is parallel to the focal plane of the microscope the analysis of diffusion from SPT data is relatively straightforward. However, in most biological samples the membranes are curved, which complicates analysis and may lead to erroneous conclusions as for the mode of lateral diffusion. Here we considered the case of lateral diffusion in tubular membranes, such as axons, dendrites or the neck of dendritic spines. Monte Carlo simulations allowed us to evaluate the error in diffusion coefficient (D) calculation if the curvature is not taken into account. The underestimation is determined by the diameter of the tubular surface, the frequency of image acquisition and the degree of mobility itself. We found that projected trajectories give estimates that are 25 to 50% lower than the real D in case of 2D-SPT over the tubular surface. The use of 3D-SPT improved the measurements if the frequency of image acquisition was fast enough in relation to the mobility of the molecules and the diameter of the tube. Nevertheless, the calculation of D from the components of displacements in the axis of the tubular structure gave accurate estimate of D, free of geometrical artefacts. We show the application of this approach to analyze the diffusion of a lipid on model tubular membranes and of a membrane-bound GFP on neurites from cultured rat hippocampal neurons. PMID:21980531

  3. Protocatechuic Aldehyde Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Nox-Mediated Oxidative Stress and Renal Inflammation.

    PubMed

    Gao, Li; Wu, Wei-Feng; Dong, Lei; Ren, Gui-Ling; Li, Hai-Di; Yang, Qin; Li, Xiao-Feng; Xu, Tao; Li, Zeng; Wu, Bao-Ming; Ma, Tao-Tao; Huang, Cheng; Huang, Yan; Zhang, Lei; Lv, Xiongwen; Li, Jun; Meng, Xiao-Ming

    2016-01-01

    Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress, and programmed cell death of renal tubular epithelial cells, all of which lead to high mortality rates in patients. In this study, we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza (Lamiaceae). Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA blocks cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients receiving cisplatin treatment.

  4. Protocatechuic Aldehyde Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Nox-Mediated Oxidative Stress and Renal Inflammation

    PubMed Central

    Gao, Li; Wu, Wei-Feng; Dong, Lei; Ren, Gui-Ling; Li, Hai-Di; Yang, Qin; Li, Xiao-Feng; Xu, Tao; Li, Zeng; Wu, Bao-Ming; Ma, Tao-Tao; Huang, Cheng; Huang, Yan; Zhang, Lei; Lv, Xiongwen; Li, Jun; Meng, Xiao-Ming

    2016-01-01

    Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress, and programmed cell death of renal tubular epithelial cells, all of which lead to high mortality rates in patients. In this study, we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza (Lamiaceae). Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA blocks cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients receiving cisplatin treatment. PMID:27999546

  5. SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model

    PubMed Central

    Xu, Siqi; Wei, Siwei; Dai, Xingui

    2016-01-01

    Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI. PMID:28003866

  6. Synchronized renal tubular cell death involves ferroptosis.

    PubMed

    Linkermann, Andreas; 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

    2014-11-25

    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.

  7. Basic fibroblast growth factor reduces functional and structural damage in chronic kidney disease.

    PubMed

    Villanueva, Sandra; Contreras, Felipe; Tapia, Andrés; Carreño, Juan E; Vergara, Cesar; Ewertz, Ernesto; Cespedes, Carlos; Irarrazabal, Carlos; Sandoval, Mauricio; Velarde, Victoria; Vio, Carlos P

    2014-02-15

    Chronic kidney disease (CKD) is characterized by loss of renal function. The pathological processes involved in the progression of this condition are already known, but the molecular mechanisms have not been completely explained. Recent reports have shown the intrinsic capacity of the kidney to undergo repair after acute injury through the reexpression of repairing proteins (Villanueva S, Cespedes C, Vio CP. Am J Physiol Regul Integr Comp Physiol 290: R861-R870, 2006). Stimulation with basic fibroblast growth factor (bFGF) could accelerate this process. However, it is not known whether bFGF can induce this phenomenon in kidney cells affected by CKD. Our aim was to study the evolution of renal damage in animals with CKD treated with bFGF and to relate the amount of repairing proteins with renal damage progression. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy (NPX) and treated with bFGF (30 μg/kg, NPX+bFGF); a control NPX group was treated with saline (NPX+S). Animals were euthanized 35 days after bFGF administration. Functional effects were assessed based on serum creatinine levels; morphological damage was assessed by the presence of macrophages (ED-1), interstitial α-smooth muscle actin (α-SMA), and interstitial collagen through Sirius red staining. The angiogenic factors VEGF and Tie-2 and the epithelial/tubular factors Ncam, bFGF, Pax-2, bone morphogenic protein-7, Noggin, Lim-1, Wnt-4, and Smads were analyzed. Renal stem cells were evaluated by Oct-4. We observed a significant reduction in serum creatinine levels, ED-1, α-SMA, and Sirius red as well as an important induction of Oct-4, angiogenic factors, and repairing proteins in NPX+bFGF animals compared with NPX+S animals. These results open new perspectives toward reducing damage progression in CKD.

  8. Albumin-bound fatty acids but not albumin itself alter redox balance in tubular epithelial cells and induce a peroxide-mediated redox-sensitive apoptosis.

    PubMed

    Ruggiero, Christine; Elks, Carrie M; Kruger, Claudia; Cleland, Ellen; Addison, Kaity; Noland, Robert C; Stadler, Krisztian

    2014-04-15

    Albuminuria is associated with metabolic syndrome and diabetes. It correlates with the progression of chronic kidney disease, particularly with tubular atrophy. The fatty acid load on albumin significantly increases in obesity, presenting a proinflammatory environment to the proximal tubules. However, little is known about changes in the redox milieu during fatty acid overload and how redox-sensitive mechanisms mediate cell death. Here, we show that albumin with fatty acid impurities or conjugated with palmitate but not albumin itself compromised mitochondrial and cell viability, membrane potential and respiration. Fatty acid overload led to a redox imbalance which deactivated the antioxidant protein peroxiredoxin 2 and caused a peroxide-mediated apoptosis through the redox-sensitive pJNK/caspase-3 pathway. Transfection of tubular cells with peroxiredoxin 2 was protective and mitigated apoptosis. Mitochondrial fatty acid entry and ceramide synthesis modulators suggested that mitochondrial β oxidation but not ceramide synthesis may modulate lipotoxic effects on tubular cell survival. These results suggest that albumin overloaded with fatty acids but not albumin itself changes the redox environment in the tubules, inducing a peroxide-mediated redox-sensitive apoptosis. Thus, mitigating circulating fatty acid levels may be an important factor in both preserving redox balance and preventing tubular cell damage in proteinuric diseases.

  9. Senescence marker protein-30/gluconolactonase deficiency exacerbates diabetic nephropathy through tubular injury in a mouse model of type 1 diabetes

    PubMed Central

    Okada, Hiroshi; Senmaru, Takafumi; Fukui, Michiaki; Kondo, Yoshitaka; Ishigami, Akihito; Maruyama, Naoki; Obayashi, Hiroshi; Yamazaki, Masahiro; Nakamura, Naoto; Hasegawa, Goji

    2015-01-01

    Aims/Introduction Senescence marker protein-30 (SMP30) is abundantly expressed in renal proximal tubule cells, but its expression decreases with age. Previous studies have shown that reduced SMP30 expression could contribute to aging-associated deterioration of cellular function and tissue injury. In the present study, we investigated the effects of SMP30 deficiency on the pathogenesis of diabetic nephropathy. Materials and Methods Diabetes was induced using streptozotocin in male SMP30 knockout mice (KO) and wild-type mice at 7 weeks-of-age. Vitamin C was added to the drinking water to prevent vitamin C deficiency in KO mice. The mice were killed 12 weeks after the induction of diabetes. Results Urinary biomarkers for proximal tubule damage were significantly increased in non-diabetic KO mice compared with wild-type mice. Furthermore, diabetes-induced tubular damage was significantly exacerbated by SMP30 deletion. Morphological analysis showed a link between cortical tubulointerstitial fibrosis area and the degree of tubular damage. However, SMP30 deletion did not affect mesangial expansion. Tubular injury was associated with accumulation of hypoxia-inducible factor-1α and increased hypoxia-inducible factor-1α targeted gene expression. SMP30 deletion initiated oxidative stress; however, it did not exacerbate the oxidative stress seen in diabetic mice. In contrast, tubular inflammation was associated with SMP30 deletion only in diabetic mice. Conclusions Based on this evidence, we concluded that SMP30 deficiency exacerbates proximal tubule injury in diabetic mice. Decreased SMP30 could contribute to the increased incidence of various chronic kidney diseases, including diabetic nephropathy, with age. PMID:25621131

  10. Acute psychotic disorder and hypoglycemia.

    PubMed

    Singh, S K; Agrawal, J K; Srivastava, A S; Bhardwaj, V K; Bose, B S

    1994-04-01

    A variable array of neuroglycopenic symptoms are frequently encountered in the hypoglycemic stage, but acute psychotic disorders are quite rare. A fifty five year old female presented with an acute psychosis following oral sulfonylurea induced hypoglycemia without preceding features of adrenomedullary stimulation. This case report suggests that an acute and transient psychotic disorder may be an important neuroglycopenic feature and its early recognition protects the patient from severe hypoglycemic brain damage in a state of hypoglycemia unawareness.

  11. Kinetics of carbendazim degradation in a horizontal tubular biofilm reactor.

    PubMed

    Alvarado-Gutiérrez, María Luisa; Ruiz-Ordaz, Nora; Galíndez-Mayer, Juvencio; Santoyo-Tepole, Fortunata; Curiel-Quesada, Everardo; García-Mena, Jaime; Ahuatzi-Chacón, Deifilia

    2016-12-22

    The fungicide carbendazim is an ecotoxic agent affecting aquatic biota. Due to its suspected hormone-disrupting effects, it is considered a "priority hazard substance" by the Water Framework Directive of the European Commission, and its degradation is of major concern. In this work, a horizontal tubular biofilm reactor (HTBR) operating in plug-flow regime was used to study the kinetics of carbendazim removal by an acclimated microbial consortium. The reactor was operated in steady state continuous culture at eight different carbendazim loading rates. The concentrations of the fungicide were determined at several distances of the HTBR. At the loading rates tested, the highest instantaneous removal rates were observed in the first section of the tubular biofilm reactor. No evidence of inhibition of the catabolic activity of the microbial community was found. Strains of the genera Flectobacillus, Klebsiella, Stenotrophomonas, and Flavobacterium were identified in the biofilm; the last three degrade carbendazim in axenic culture.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Numerical simulation of premixed H2-air cellular tubular flames

    NASA Astrophysics Data System (ADS)

    Hall, Carl Alan; Wendell Pitz, Robert

    2016-03-01

    The detailed flame structure of laminar premixed cellular flames in the tubular domain is simulated in 2D using a fully-implicit primitive variable finite difference formulation that includes multicomponent transport and detailed chemical kinetics. Numerical results for H2/air flames are presented and compared against spatially resolved experimental measurements of temperature and chemical species including atomic H and OH. The experimental results compare well for flame structure and cell number, despite the numerical model under-predicting the peak temperature by 200 K. Numerical experiments were performed to assess the ability for cellular tubular flames to impact experimental and numerical investigations of practical flames. The cellular flame structure is found to provide a highly sensitive geometry that is useful for validating diffusive transport modelling approximations. This capability is exemplified through the development of a simple and accurate approximation for thermal diffusion (i.e. the Soret effect) that is suitable for practical combustion codes.

  17. 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.

  18. Blood-Induced Joint Damage

    PubMed Central

    Roosendaal, Goris; Jansen, Nathalie W.D.; Lafeber, Floris P.J.G.; Mastbergen, Simon C.

    2013-01-01

    Objective. Four days of blood exposure leads to irreversible cartilage damage in vitro. In contrast, intermittent intra-articular blood injections twice a week during 4 weeks (mimicking micro-bleeds) in a canine model resulted in transient damage only. In this study, it was evaluated whether acute joint bleeds are more harmful than micro-bleeds in a canine model of knee arthropathy. Design. Seven dogs received 4 sequential daily intra-articular blood injections twice in 2 weeks (mimicking 2 acute 4-day joint bleeds). Seven other dogs received the same blood load but in a total of 8 injections intermittently over the 4-week period with at least 1 day in between (mimicking micro-bleeds over the same timespan). Contralateral knees served as controls. Ten weeks after the last injection cartilage matrix turnover and synovial inflammation were evaluated. Results. Only after the acute joint bleeds the release of newly formed and total (resident) cartilage matrix glycosaminoglycans were increased (P = 0.04 and P = 0.01, respectively). Furthermore, in animals with the acute joint bleeds cartilage glycosaminoglycan content was decreased (P = 0.01) and not in animals with micro-bleeds. Mild synovial inflammation was observed in both groups (both P < 0.0001) but was not different between groups. Conclusions. In contrast to micro-bleeds, 2 acute joint bleeds lead to prolonged cartilage damage independent of the level of synovial inflammation. This model suggests that micro-bleeds are less devastating than acute joint bleeds with respect to joint damage, which might be of relevance to treatment of joint bleeds in clinical practice. PMID:26069675

  19. Acute laminitis.

    PubMed

    Baxter, G M

    1994-12-01

    Laminitis is an inflammation of the sensitive laminae along the dorsal aspect of the digit and is considered to be a secondary complication of several predisposing or primary factors. Affected horses are usually very lame, have increased digital pulses, are painful to hoof testers along the toe of the foot, and have evidence of downward rotation or distal displacement of the distal phalanx present on radiographs. Treatments for acute laminitis include anti-inflammatory drugs, anti-endotoxin therapy, vasodilators, antithrombotic therapy, corrective trimming and shoeing, and surgical procedures. Treatment regimens are very controversial and the true efficacy of these treatments is unknown. The quality of laminae damage that occurs with laminitis, however, probably has greater influence on the success of treatment and outcome of the horse than the treatment regimen itself.

  20. Role of CDK5/cyclin complexes in ischemia-induced death and survival of renal tubular cells.

    PubMed

    Guevara, Tatiana; Sancho, Mónica; Pérez-Payá, Enrique; Orzáez, Mar

    2014-01-01

    Ischemia reperfusion processes induce damage in renal tubules and compromise the viability of kidney transplants. Understanding the molecular events responsible for tubule damage and recovery would help to develop new strategies for organ preservation. CDK5 has been traditionally considered a neuronal kinase with dual roles in cell death and survival. Here, we demonstrate that CDK5 and their regulators p35/p25 and cyclin I are also expressed in renal tubular cells. We show that treatment with CDK inhibitors promotes the formation of pro-survival CDK5/cyclin I complexes and enhances cell survival upon an ischemia reperfusion pro-apoptotic insult. These findings support the benefit of treating with CDK inhibitors for renal preservation, assisting renal tubule protection.

  1. Urinary granzyme A mRNA is a biomarker to diagnose subclinical and acute cellular rejection in kidney transplant recipients.

    PubMed

    van Ham, S Marieke; Heutinck, Kirstin M; Jorritsma, Tineke; Bemelman, Fréderike J; Strik, Merel C M; Vos, Wim; Muris, Jettie J F; Florquin, Sandrine; Ten Berge, Ineke J M; Rowshani, Ajda T

    2010-11-01

    The distinction between T-cell-mediated rejection (TCMR) and other causes of kidney transplant dysfunction such as tubular necrosis requires biopsy. Subclinical rejection (SCR), an established risk factor for chronic allograft dysfunction, can only be diagnosed by protocol biopsy. A specific non-invasive biomarker to monitor immunological graft status would facilitate diagnosis and treatment of common transplantation-related complications. To identify possible markers, we measured urinary mRNA levels of several cytolytic proteins by quantitative PCR. Our cohort of 70 renal transplant recipients had biopsy proven type I and type II TCMR, acute tubular necrosis, SCR, calcineurin inhibitor-toxicity, cytomegalovirus infection, and stable graft function with normal histology. Granzyme A (GzmA) mRNA was significantly higher in subclinical and acute cellular rejection compared to patients with stable grafts or those with tubular necrosis with 80% sensitivity and up to 100% specificity. Granzyme B and perforin mRNA levels could significantly discriminate acute rejection from stable or tubular necrosis, but were not significantly elevated during SCR. Importantly, only GzmA mRNA remained below detection limits from grafts that were stable and most with tubular necrosis. Hence, the presented data indicate that urinary GzmA mRNA levels may entail a diagnostic non-invasive biomarker to distinguish patients with subclinical and acute cellular rejection from those with tubular necrosis or stable grafts.

  2. 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.

  3. The hybrid ring tubular external fixator: a biomechanical study.

    PubMed

    Stein, H; Mosheiff, R; Baumgart, F; Frigg, R; Perren, S M; Cordey, J

    1997-06-01

    OBJECTIVE: To measure and compare the mechanical properties in bending of the four-ring, and three-ring/one-tube hybrid external fixation frames. DESIGN. IN VITRO: measurements of the mechanical behaviour of ring and ring-tubular external fixation frames. In the latter, one ring of the full circular frame was replaced by one tube and Schanz screws. BACKGROUND: The mechanical properties of the classical Ilizarov four-ring external fixation frames has been compared to those of other external fixation frames by various authors. However, in clinical practice the hybrid fixation frame is being used with increasing frequency. Therefore the mechanical properties of the latter are of immediate interest and clinical value. METHODS: On explanted sheep tibiae with single and double osteotomies, frame stiffness in the four-point bending mode was measured at different K-wire tensions, comparing the values obtained from four-ring frames, to those of three-ring-tubular hybrid frames. These measurements were made under conditions of (a) bone distraction (BD), and (b) segment transport (ST), both at the initial and final stages of this procedure. RESULTS: In circular frames, frame stiffness in bending for increasing K-wire tension showed a Gaussian distribution both in distraction and post-ST with an optimum at 1000 N. In ring tubular hybrid frames, however, frame stiffness showed a more linear relationship to K-wire tension. CONCLUSIONS: In the four-ring Ilizarov external fixation frame, the exchange of one ring with one tube and one Schanz screw both reduced frame stiffness in bending and converted to linear its relationship to K-wire tension. RELEVANCE: Under clinical conditions, the use of a similar ring tubular hybrid external fixator allows the adjustment of frame stiffness in a simple and practical way. This is not the case with the original ring fixation frame.

  4. 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

  5. Solar energy utilisation and evacuated tubular solar collectors

    NASA Astrophysics Data System (ADS)

    Parand, Foroutan

    Four types of evacuated tubular solar collectors have been constructed and their performance evaluated. The characteristics of the collectors are then compared and their design strengths assessed. One of the designs, a flat absorber with a single glass cover using glass to metal seals was found to have the best performance among the four designs which included a dewar vessel type collector, a heat pipe collector and a black liquid collector with an optical efficiency of 87.7 pct. and an overall heat loss coefficient of 12.3 Wm(exp -2)/C. The performance of the dewar vessel type and black liquid collectors was found to be comparable to the glass to metal seal collector. A detailed analysis of the optical and thermal processes in evacuated tubular collectors was made. On the basis of this analysis a computer simulation model using a finite difference technique has been developed to predict the performance of evacuated tubular collectors. The computer simulation results are then compared with the test results. For the majority of the tests the discrepancy between the simulation and the test results was within the error band of the test results (maximum 12 pct.). For the published test results the maximum discrepancy for operating temperature below 100 C was found to be 6 pct. The computer simulation model was compared with other published models and its advantages and disadvantages discussed. In some analytical and semi-analytical simulation models the energy absorbed by the glass cover and the heat loss from joints and supports has to be ignored. The present model has none of these deficiencies and more complex designs can be simulated. The developed computer simulation program might be used as an aid in the design of evacuated tubular collectors. Using the computer simulation, a parametric study of the three commmercially available collectors was made. The results are discussed and the areas of improvement are identified.

  6. 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.

  7. 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.

  8. 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.

  9. Structural study of non-premixed tubular hydrocarbon flames

    SciTech Connect

    Hu, Shengteng; Pitz, Robert W.

    2009-01-15

    Tubular non-premixed flames are formed by a uniquely designed opposed tubular burner. Structural measurements of hydrocarbon flames are conducted using the laser-induced Raman scattering technique. Temperature and major species concentrations are recorded for flames produced by 30% CH{sub 4}/N{sub 2} and 15% C{sub 3}H{sub 8}/N{sub 2} burning against air. Numerical simulations of these flames with detailed chemistry show good agreement between the measured and simulated results. By comparing the numerical results of the tubular curved flames to those of the opposed-jet planar flames, it is shown that flame curvature towards the fuel stream strongly effects the temperature ({+-}80 K) of flames with low fuel Lewis number (15% H{sub 2}/N{sub 2}, Le{sub f} = 0.41). The effect of curvature on flames with high (15% C{sub 3}H{sub 8}/N{sub 2}, Le{sub f} = 1.51) and near-unity (30% CH{sub 4}/N{sub 2}, Le{sub f}{approx_equal}1) fuel Lewis numbers is much less. (author)

  10. Tubular cationized pullulan hydrogels as local reservoirs for plasmid DNA.

    PubMed

    San Juan, Aurélie; Ducrocq, Grégory; Hlawaty, Hanna; Bataille, Isabelle; Guénin, Erwann; Letourneur, Didier; Feldman, Laurent J

    2007-12-01

    In the present study, we measured the ability of various cationized pullulan tubular hydrogels to retain plasmid DNA, and tested the ability of retained plasmid DNA to transfect vascular smooth muscle cells (VSMCs). Cationized pullulans were obtained by grafting at different charge densities ethylamine (EA) or diethylaminoethylamine (DEAE) on the pullulan backbone. Polymers were characterized by elemental analysis, acid-base titration, size exclusion chromatography, Fourier-transform infrared spectroscopy, and proton nuclear magnetic resonance. The complexation of cationized pullulans in solution with plasmid DNA was evidenced by fluorescence quenching with PicoGreen. Cationized pullulans were then chemically crosslinked with phosphorus oxychloride to obtain tubular cationized pullulan hydrogels. Native pullulan tubes did not retain loaded plasmid DNA. In contrast, the ability of cationized pullulan tubes to retain plasmid DNA was dependent on both the amine content and the type of amine. The functional integrity of plasmid DNA in cationized pullulan tubes was demonstrated by in vitro transfection of VSMCs. Hence, cationized pullulan hydrogels can be designed as tubular structures with high affinity for plasmid DNA, which may provide new biomaterials to enhance the efficiency of local arterial gene transfer strategies.

  11. 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.

  12. Plastic deformation of tubular crystals by dislocation glide

    NASA Astrophysics Data System (ADS)

    Beller, Daniel A.; Nelson, David R.

    2016-09-01

    Tubular crystals, two-dimensional lattices wrapped into cylindrical topologies, arise in many contexts, including botany and biofilaments, and in physical systems such as carbon nanotubes. The geometrical principles of botanical phyllotaxis, describing the spiral packings on cylinders commonly found in nature, have found application in all these systems. Several recent studies have examined defects in tubular crystals associated with crystalline packings that must accommodate a fixed tube radius. Here we study the mechanics of tubular crystals with variable tube radius, with dislocations interposed between regions of different phyllotactic packings. Unbinding and separation of dislocation pairs with equal and opposite Burgers vectors allow the growth of one phyllotactic domain at the expense of another. In particular, glide separation of dislocations offers a low-energy mode for plastic deformations of solid tubes in response to external stresses, reconfiguring the lattice step by step. Through theory and simulation, we examine how the tube's radius and helicity affects, and is in turn altered by, the mechanics of dislocation glide. We also discuss how a sufficiently strong bending rigidity can alter or arrest the deformations of tubes with small radii.

  13. Vascular versus tubular renin: role in kidney development

    PubMed Central

    Nagalakshmi, Vidya K.; Li, Minghong; Sigmund, Curt D.; Gomez, R. Ariel

    2015-01-01

    Renin, the key regulated enzyme of the renin-angiotensin system regulates blood pressure, fluid-electrolyte homeostasis, and renal morphogenesis. Whole body deletion of the renin gene results in severe morphological and functional derangements, including thickening of renal arterioles, hydronephrosis, and inability to concentrate the urine. Because renin is found in vascular and tubular cells, it has been impossible to discern the relative contribution of tubular versus vascular renin to such a complex phenotype. Therefore, we deleted renin independently in the vascular and tubular compartments by crossing Ren1c fl/fl mice to Foxd1-cre and Hoxb7-cre mice, respectively. Deletion of renin in the vasculature resulted in neonatal mortality that could be rescued with daily injections of saline. The kidneys of surviving mice showed the absence of renin, hypertrophic arteries, hydronephrosis, and negligible levels of plasma renin. In contrast, lack of renin in the collecting ducts did not affect kidney morphology, intra-renal renin, or circulating renin in basal conditions or in response to a homeostatic stress, such as sodium depletion. We conclude that renin generated in the renal vasculature is fundamental for the development and integrity of the kidney, whereas renin in the collecting ducts is dispensable for normal kidney development and cannot compensate for the lack of renin in the vascular compartment. Further, the main source of circulating renin is the kidney vasculature. PMID:26246508

  14. Defining the acute kidney injury and repair transcriptome.

    PubMed

    Kumar, Sanjeev; Liu, Jing; McMahon, Andrew P

    2014-07-01

    The mammalian kidney has an intrinsic ability to repair after significant injury. However, this process is inefficient: patients are at high risk for the loss of kidney function in later life. No therapy exists to treat established acute kidney injury (AKI) per se: strategies to promote endogenous repair processes and retard associated fibrosis are a high priority. Whole-organ gene expression profiling has been used to identify repair responses initiated with AKI, and factors that may promote the transition from AKI to chronic kidney disease. Transcriptional profiling has shown molecular markers and potential regulatory pathways of renal repair. Activation of a few key developmental pathways has been reported during repair. Whether these are comparable networks with similar target genes with those in earlier nephrogenesis remains unclear. Altered microRNA profiles, persistent tubular injury responses, and distinct late inflammatory responses highlight continuing kidney pathology. Additional insights into injury and repair processes will be gained by study of the repair transcriptome and cell-specific translatome using high-resolution technologies such as RNA sequencing and translational profiling tailored to specific cellular compartments within the kidney. An enhanced understanding holds promise for both the identification of novel therapeutic targets and biomarker-based evaluation of the damage-repair process.

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

    PubMed

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

    2016-02-01

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

  16. Modifying Radiation Damage

    PubMed Central

    Kim, Kwanghee; McBride, William H.

    2011-01-01

    Radiation leaves a fairly characteristic footprint in biological materials, but this is rapidly all but obliterated by the canonical biological responses to the radiation damage. The innate immune recognition systems that sense “danger” through direct radiation damage and through associated collateral damage set in motion a chain of events that, in a tissue compromised by radiation, often unwittingly result in oscillating waves of molecular and cellular responses as tissues attempt to heal. Understanding “nature’s whispers” that inform on these processes will lead to novel forms of intervention targeted more precisely towards modifying them in an appropriate and timely fashion so as to improve the healing process and prevent or mitigate the development of acute and late effects of normal tissue radiation damage, whether it be accidental, as a result of a terrorist incident, or of therapeutic treatment of cancer. Here we attempt to discuss some of the non-free radical scavenging mechanisms that modify radiation responses and comment on where we see them within a conceptual framework of an evolving radiation-induced lesion. PMID:20583981

  17. Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-κB pathway in ischemia/reperfusion-induced acute kidney injury

    SciTech Connect

    Lee, Jae-Won Kim, Sun Chul Ko, Yoon Sook Lee, Hee Young Cho, Eunjung Kim, Myung-Gyu Jo, Sang-Kyung Cho, Won Yong Kim, Hyoung Kyu

    2014-02-07

    Highlights: • Paricalcitol. • Attenuation of renal inflammation. • Modulation of TLR4-NF-κB signaling. - Abstract: Background: The pathophysiology of ischemic acute kidney injury (AKI) is thought to include a complex interplay between vascular endothelial cell dysfunction, inflammation, and tubular cell damage. Several lines of evidence suggest a potential anti-inflammatory effect of vitamin D in various kidney injury models. In this study, we investigated the effect of paricalcitol, a synthetic vitamin D analog, on renal inflammation in a mouse model of ischemia/reperfusion (I/R) induced acute kidney injury (AKI). Methods: Paricalcitol was administered via intraperitoneal (IP) injection at 24 h before ischemia, and then I/R was performed through bilateral clamping of the renal pedicles. Twenty-four hours after I/R, mice were sacrificed for the evaluation of injury and inflammation. Additionally, an in vitro experiment using HK-2 cells was also performed to examine the direct effect of paricalcitol on tubular cells. Results: Pre-treatment with paricalcitol attenuated functional deterioration and histological damage in I/R induced AKI, and significantly decreased tissue neutrophil and macrophage infiltration and the levels of chemokines, the pro-inflammatory cytokine interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). It also decreased IR-induced upregulation of Toll-like receptor 4 (TLR4), and nuclear translocation of p65 subunit of NF-κB. Results from the in vitro study showed pre-treatment with paricalcitol suppressed the TNF-α-induced depletion of cytosolic IκB in HK-2 cells. Conclusion: These results demonstrate that pre-treatment with paricalcitol has a renoprotective effect in ischemic AKI, possibly by suppressing TLR4-NF-κB mediated inflammation.

  18. Analysis of constant tissue remodeling in Syrian hamster Harderian gland: intra-tubular and inter-tubular syncytial masses.

    PubMed

    Coto-Montes, Ana; García-Macía, Marina; Caballero, Beatriz; Sierra, Verónica; Rodríguez-Colunga, María J; Reiter, Russel J; Vega-Naredo, Ignacio

    2013-05-01

    The Syrian hamster Harderian gland (HG) has a marked sexual dimorphism and exhibits an extraordinary rate of porphyrinogenesis. The physiological oxidative stress, derived from constant porphyrin production, is so high that the HG needs additional survival autophagic mechanisms to fight against this chronic exposure, provoking the triggering of a holocrine secretion in female glands that forms two types of secretory masses: intra-tubular-syncytial and inter-tubular-syncytial masses. The aim of this work was to study the development of this inter-tubular holocrine secretion. To approach this task, we have considered that the steps developed during the formation of the so-called invasive masses consist of the growth of epithelial cells, cell detachment from the basal lamina and invasion of surrounding tissues. The presence of these masses, particularly in the female HG, are closely linked to sexual dimorphism in redox balance and to alterations in the expression of certain factors such as cytokeratins, P-cadherin, matrix metalloproteinases, cathepsin H, proliferating cell nuclear antigen, p53, CD-31 and vascular endothelial growth factor, which seem to be involved in tissue remodeling. The results document unusual mechanisms of secretion in Syrian hamster HG: an extraordinary system of massive secretion through the conjunctive tissue, disrupting the branched structure of the gland.

  19. Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

    SciTech Connect

    Yu, Ge; Wan, Rong; Hu, Yanling; Ni, Jianbo; Yin, Guojian; Xing, Miao; Shen, Jie; Tang, Maochun; Chen, Congying; Fan, Yuting; Xiao, Wenqin; Zhao, Yan; Wang, Xingpeng; and others

    2014-01-31

    Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.

  20. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma

    PubMed Central

    Hutchison, Colin A.; Batuman, Vecihi; Behrens, Judith; Bridoux, Frank; Sirac, Christophe; Dispenzieri, Angela; Herrera, Guillermo A.; Lachmann, Helen; Sanders, Paul W.

    2012-01-01

    Renal failure remains a principal cause of morbidity for patients with multiple myeloma. Once reversible factors such as hypercalcemia have been corrected, the most common cause of severe renal failure in these patients is a tubulointerstitial pathology that results from the very high circulating concentrations of monoclonal immunoglobulin free light chains. These endogenous proteins can result in isolated proximal tubule cell cytotoxicity, tubulointerstitial nephritis and cast nephropathy (myeloma kidney). Less frequently, high levels of free light chains can lead to immunoglobulin light chain amyloidosis and light chain deposition disease, although these conditions are usually associated with insidious progression of renal failure rather than acute kidney injury. Unless there is rapid intervention, progressive and irreversible damage occurs, particularly interstitial fibrosis and tubular atrophy. Despite advances in our understanding of the pathogenesis of these processes there has been a gap in translating these achievements into improved patient outcomes. The International Kidney and Monoclonal Gammopathy Research Group was formed to address this need. In this Review, we discuss the mechanisms of disease and diagnostic approaches to patients with acute kidney injury complicating multiple myeloma. PMID:22045243

  1. 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.

  2. Cystitis - acute

    MedlinePlus

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

  3. Urinary enzymes and low molecular weight proteins as markers of tubular dysfunction.

    PubMed

    Jung, K

    1994-11-01

    Reference intervals of different tubular markers, that is, low molecular weight proteins and urinary enzymes, show divergent data and wide ranges. The problems in establishing reference intervals for the tubular markers are caused by the necessarily different analytical methods. Also, the general rules of determining reference limits as well as the numerous physiological variables influencing tubular function are often not sufficiently taken into consideration. Compared to blood components, urinary tubular markers show a wide variability of values. This is due to the fact that the excretion of enzymes and proteins into urine represents an excretion into an open system. The influences of variables like age, sex, physical exercise, different urine flow rates, and biorhythms are immediately reflected by changed excretion rates of tubular markers. The problems occurring when the second morning urine sample is being used as a "standardized" collection method and the basis to characterize tubular function by analyte/creatinine ratios are discussed in this paper.

  4. [Acute radiation injury].

    PubMed

    Saito, Tsutomu

    2012-03-01

    Cell death due to DNA damage by ionizing radiation causes acute radiation injury of tissues and organs. Frequency and severity of the injuries increase according to dose increase, when the dose becomes more than threshold dose. The threshold dose of acute human radiation death is 1 Gy and LD50 of human is 4 Gy. Human dies due to the cerebrovascular syndrome, the gastrointestinal syndrome or the hematopoetic syndrome, when he received more than 20 Gy, 10-20 Gy or 3-8 Gy to his total body, respectively. Any tissue or organ, including embryo and fetus, does not show the acute injury, when it received less than 100 mSv. Acute injuries are usually reversible, and late injuries are sometimes irreversible.

  5. Alkaline phosphatase as a treatment of sepsis-associated acute kidney injury.

    PubMed

    Peters, Esther; van Elsas, Andrea; Heemskerk, Suzanne; Jonk, Luigi; van der Hoeven, Johannes; Arend, Jacques; Masereeuw, Rosalinde; Pickkers, Peter

    2013-01-01

    Currently there are no pharmacological therapies licensed to treat sepsis-associated acute kidney injury (AKI). Considering the high incidence and mortality of sepsis-associated AKI, there is an urgent medical need to develop effective pharmacological interventions. Two phase II clinical trials recently demonstrated beneficial effects of the enzyme alkaline phosphatase (AP). In critically ill patients with sepsis-associated AKI, treatment with AP reduced the urinary excretion of tubular injury biomarkers and plasma markers of inflammation, which was associated with improvement of renal function. The dephosphorylating enzyme, AP, is endogenously present in the renal proximal tubule apical membrane but becomes depleted during ischemia-induced AKI, thereby possibly contributing to further renal damage. The exact mechanism of action of AP in AKI is unknown, but might be related to detoxification of circulating lipopolysaccharide and other proinflammatory mediators that lose their proinflammatory effects after dephosphorylation. Alternatively, tissue damage associated with systemic inflammation might be attenuated by an AP-mediated effect on adenosine metabolism. Adenosine is a signaling molecule that has been shown to protect the body from inflammation-induced tissue injury, which is derived through dephosphorylation of ATP. In this Perspectives article, we discuss the clinical activity of AP and its putative molecular modes of action, and we speculate on its use to treat and possibly prevent sepsis-associated AKI.

  6. Expression and Function of Interleukin-1β-Induced Neutrophil Gelatinase-Associated Lipocalin in Renal Tubular Cells

    PubMed Central

    Mamiya, Ryo; Tsuchiya, Hisashi; Kitanaka, Taku; Namba, Shinichi; Kitanaka, Nanako; Okabayashi, Ken; Narita, Takanori; Sugiya, Hiroshi

    2016-01-01

    Acute kidney injury (AKI) is characterized by a sudden loss of renal function. Early recognition of AKI, especially in critically ill patients, is essential for adequate therapy. Currently, neutrophil gelatinase-associated lipocalin (NGAL) is considered to be an effective biomarker of AKI; however, the regulation of its expression and function in renal tubular cells remains unclear. In this study, we investigated the regulation of the expression and function of NGAL in IL-1β-treated Madin–Darby canine kidney (MDCK) cells as a model of renal tubular cells. IL-1β induced a disturbance in the localization of E-cadherin and zonaoccludin-1 (ZO-1). The transepithelial electrical resistance (TER) also decreased 5 days after IL-1β treatment. IL-1β induced NGAL mRNA expression and protein secretion in a time- and dose-dependent manner, which occurred faster than the decrease in TER. In the presence of ERK1/2 and p38 inhibitors, IL-1β-induced NGAL mRNA expression and protein secretion were significantly attenuated. In the presence of recombinant NGAL, IL-1β-induced disturbance in the localization of E-cadherin and ZO-1 was attenuated, and the decrease in TER was partially maintained. These results suggest that NGAL can be used as a biomarker for AKI and that it functions as a protector from AKI. PMID:27851800

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

    SciTech Connect

    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.

  8. Minimally invasive tubular access for posterior cervical foraminotomy

    PubMed Central

    Branch, Byron C.; Hilton, Donald L.; Watts, Clark

    2015-01-01

    Background: Minimally invasive tubular access for posterior cervical foraminotomy can be an effective and safe technique for decompression of the nerve root utilizing minimally invasive muscle splitting with routine outpatient discharge. This technique has come under scrutiny calling into question the associated learning curve, a subjective limited exposure provided, and an argument that the risks and complications are largely unknown. In response to previously published critiques, this study aims to describe the outcomes and complications associated with this technique in a large patient series. Methods: A retrospective chart review was performed from 1999 to 2013 capturing a single surgeon's experience with the minimally invasive tubular access for posterior cervical foraminotomy technique from a single institution, encompassing 463 patients. Surgical outcome documented at follow-up and complications were obtained from this patient series. Additional variables analyzed include: Hospital length of stay, number of levels operated, targeted root for decompression, side operated, length of surgery, and estimated blood loss. Results: Outpatient discharge was achieved in 91.6% of cases. There were 10 complications (2.2%) among the 463 patients undergoing this technique from 1999 to 2013. Patients were followed for an average of 1 year and 2 months postoperatively. Improvement from the preoperative condition was observed in 98.2% of patients and excellent outcomes with patients reporting complete relief of symptoms with no or mild residual discomfort was seen in 92.2%. Conclusions: Compared with open techniques, minimally invasive tubular access for posterior cervical foraminotomy demonstrates comparable, if not superior, complication rates, and patient outcomes. PMID:26009705

  9. 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.

  10. Vibration analysis and sound field characteristics of a tubular ultrasonic radiator.

    PubMed

    Liang, Zhaofeng; Zhou, Guangping; Zhang, Yihui; Li, Zhengzhong; Lin, Shuyu

    2006-12-01

    A sort of tubular ultrasonic radiator used in ultrasonic liquid processing is studied. The frequency equation of the tubular radiator is derived, and its radiated sound field in cylindrical reactor is calculated using finite element method and recorded by means of aluminum foil erosion. The results indicate that sound field of tubular ultrasonic radiator in cylindrical reactor appears standing waves along both its radial direction and axial direction, and amplitudes of standing waves decrease gradually along its radial direction, and the numbers of standing waves along its axial direction are equal to the axial wave numbers of tubular radiator. The experimental results are in good agreement with calculated results.

  11. Hyperammonaemia in a child with distal renal tubular acidosis.

    PubMed

    Seracini, D; Poggi, G M; Pela, I

    2005-11-01

    A 5-month-old girl with distal renal tubular acidosis (RTA) and hyperammonaemia that had lasted for 12 days, despite metabolic acidosis correction, is presented in this report. The patient showed failure to thrive, poor feeding, hypotonia and vomiting crisis in absence of inborn errors of metabolism. Probably, hyperammonaemia was the result of an imbalance between the increased ammonia synthesis, in response to metabolic acidosis, and the impaired ammonia excretion, typical of distal RTA. Our case confirms that hyperammonaemia may be observed in distal RTA, mimicking an inborn error of metabolism, and it underlines that hyperammonaemia may persist several days after metabolic acidosis correction.

  12. Functionalization of polycarbonate with proteins; open-tubular enzymatic microreactors.

    PubMed

    Ogończyk, D; Jankowski, P; Garstecki, P

    2012-08-07

    This paper examines a set of techniques for the immobilization of enzymes on the surface of microchannels fabricated in polycarbonate (PC). Our experiments identify the method that uses combined physico-chemical immobilization on a layer of polyethyleneimine (PEI) as a reproducible vista for the robust immobilization of proteins. As an example, we demonstrate the fabrication, throughput and stability of an open-tubular reactor draped with alkaline phosphatase (ALP, EC 3.1.3.1) as a model enzyme. As PC is suitable for industrial applications the method could potentially be used to immobilize proteins in numbered-up implementations.

  13. Control system architecture for robotic welding of tubular joints

    SciTech Connect

    Madsen, O.; Holm, H.; Lauridsen, J.K.

    1996-12-31

    This paper presents the architecture of a geometry model and sensor based control system for robotic welding of tubular joints. The functional architecture of the system is described with the main emphasis on the overall mode of operation of the system. Furthermore, it is described how measurements of the physical seam profile are used to update a reference geometry model, and how welding control variables are generated based on the updated reference geometry. Finally, it is illustrated how the use of a reference geometry can improve the flexibility and robustness of the system.

  14. 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.

  15. Friction factors and roughness measurements of tubular mineral membranes

    NASA Astrophysics Data System (ADS)

    René, F.; Leuliet, J. C.; Delplace, F.

    1993-08-01

    No direct measurement of the relative roughness is available for mineral porous media because of the low mechanical resistance of such materials. In this study a method for the experimental determination of the internal diameter and the equivalent roughness is proposed for different commercial membranes used in ultrafiltration and microfiltration processes. The use of classical friction factor correlations is also discussed. The main results are the estimation of the hydraulic diameter of tubular membranes and the use of a quadratic form in order to predict friction factors and the equivalent roughness with an accuracy better than 15%.

  16. Computed tomography in suspected osteoid osteomas of tubular bones

    SciTech Connect

    Herrlin, K.; Ekelund, L.; Loevdahl, R.; Persson, B.

    1982-12-01

    Six cases of suspected osteoid osteoma of tubular bones were evaluated by computed tomography (CT). In all cases a radiolucent nidus was clearly demonstrated. In two cases a radiodense center of the nidus was visualized. It is suggested that CT may replace conventional tomography in the evaluation of these lesions. Due to its ability to locate the lesion in the transverse plane, CT is superior for the exact planning of surgery to avoid unnecessary large or misdirected resections. Adequate window settings are essential in the evaluation of these lesions.

  17. Human adipose-derived mesenchymal stem cells repair cisplatin-induced acute kidney injury through antiapoptotic pathways.

    PubMed

    Yao, Weiqi; Hu, Qinyong; Ma, Yuhong; Xiong, Wenping; Wu, Tingting; Cao, Jun; Wu, Dongcheng

    2015-08-01

    Cisplatin has been hypothesized to induce nephrotoxicity through triggering the apoptosis of tubular cells; however, the drug remains widely administered for the treatment of tumors. Recently, mesenchymal stem cells (MSCs) have been demonstrated to protect the kidney from the adverse effects induced by cisplatin. The aim of the present study was to investigate the mechanisms underlying the protective effects of human adipose-derived MSCs (AD-MSCs) on kidney function and tubular cells. Sprague-Dawley rats were divided into three groups, which included the healthy controls, those subjected to cisplatin-induced acute kidney injury (AKI) for 24 h without subsequent treatment and those subjected to cisplatin-induced AKI for 24 h, followed by AD-MSC engraftment. The rats were sacrificed at day 5 and the effects were analyzed using various methods, including biochemical analysis, structural examination and cell tracking experiments. In addition, an in vitro experiment with NRK-52E cells was performed. The cells were divided into three groups, including the healthy control, cisplatin induction and cisplatin induction with co-culture of AD-MSCs, and were subsequently assessed with a Transwell assay. After culture for four days, the cells were lysed and the total protein extract was subjected to western blot analysis. Cisplatin-induced renal dysfunction and tissue damage was shown to recover following AD-MSC infusion, although there were few AD-MSCs observed around the injured kidney tubules in the kidney. When the cisplatin-treated NRK-52E cells were co-cultured with AD-MSCs, the activation of p38 and BAX were inhibited, while the expression of Bcl-2 was upregulated, as compared with the cisplatin-treated NRK-52E cells that were not co-cultured. Therefore, AD-MSCs were shown to markedly improve cisplatin-induced renal failure and tubular cells necrosis through the secretion of certain factors, which subsequently inhibited the apoptosis pathway in vitro. It was hypothesized

  18. Acute pancreatitis as a model of SIRS.

    PubMed

    Bhatia, Madhav

    2009-01-01

    Acute pancreatitis is a common clinical condition. Excessive systemic inflammatory response syndrome (SIRS) in acute pancreatitis leads to distant organ damage and multiple organ dysfunction syndrome (MODS), which is the primary cause of morbidity and mortality in this condition. Development of in vivo experimental models of acute pancreatitis and associated systemic organ damage has enabled us to study the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and associated systemic organ damage. Using these models, recent studies by us and other investigators have established the critical role played by inflammatory mediators such as TNF-a, IL-1b, IL-6, PAF, IL-10, CD40L, C5a, ICAM-1, chemokines, substance P and hydrogen sulfide in acute pancreatitis and the resultant MODS. This chapter intends to present an overview of different experimental animal models of acute pancreatitis and associated MODS and the role of inflammatory mediators in the pathogenesis of this condition.

  19. Effects of antidiuretic hormone on urinary acidification and on tubular handling of bicarbonate in the rat.

    PubMed Central

    Bichara, M; Mercier, O; Houillier, P; Paillard, M; Leviel, F

    1987-01-01

    Paired micropuncture experiments were carried out in plasma-replete volume-expanded rats to examine the acute effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on urinary acidification and tubular handling of bicarbonate and chloride. No effect was detected on the fractional absorption of water, total CO2, and chloride at end-proximal and early distal sites of superficial nephrons in intact animals; dDAVP, however, inhibited the fractional absorption of total CO2 in Henle's loop while stimulating that of chloride in thyroparathyroidectomized (TPTX) somatostatin-infused rats. In the distal tubule accessible to micropuncture, net total CO2 secretion was observed during hypotonic volume expansion, which reversed to net total CO2 absorption during dDAVP infusion in intact Wistar rats. Marked stimulation of urinary acidification occurred in all animals as attested by a fall in urine pH and bicarbonate excretion. Net acid excretion almost doubled in intact rats. We conclude that (a) antidiuretic hormone (ADH) inhibits fractional bicarbonate absorption in the thick ascending limb while stimulating that of chloride at least in TPTX somatostatin-infused rats, and (b) ADH stimulates proton secretion (or inhibits bicarbonate secretion) in the distal tubule and cortical collecting ducts, which leads to enhanced urinary acidification. PMID:3624481

  20. Acute Kidney Injury

    PubMed Central

    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

  1. Right Hemisphere Brain Damage

    MedlinePlus

    ... Language and Swallowing / Disorders and Diseases Right Hemisphere Brain Damage [ en Español ] What is right hemisphere brain ... right hemisphere brain damage ? What is right hemisphere brain damage? Right hemisphere brain damage (RHD) is damage ...

  2. Dynamic modeling of temperature change in outdoor operated tubular photobioreactors.

    PubMed

    Androga, Dominic Deo; Uyar, Basar; Koku, Harun; Eroglu, Inci

    2017-04-06

    In this study, a one-dimensional transient model was developed to analyze the temperature variation of tubular photobioreactors operated outdoors and the validity of the model was tested by comparing the predictions of the model with the experimental data. The model included the effects of convection and radiative heat exchange on the reactor temperature throughout the day. The temperatures in the reactors increased with increasing solar radiation and air temperatures, and the predicted reactor temperatures corresponded well to the measured experimental values. The heat transferred to the reactor was mainly through radiation: the radiative heat absorbed by the reactor medium, ground radiation, air radiation, and solar (direct and diffuse) radiation, while heat loss was mainly through the heat transfer to the cooling water and forced convection. The amount of heat transferred by reflected radiation and metabolic activities of the bacteria and pump work was negligible. Counter-current cooling was more effective in controlling reactor temperature than co-current cooling. The model developed identifies major heat transfer mechanisms in outdoor operated tubular photobioreactors, and accurately predicts temperature changes in these systems. This is useful in determining cooling duty under transient conditions and scaling up photobioreactors. The photobioreactor design and the thermal modeling were carried out and experimental results obtained for the case study of photofermentative hydrogen production by Rhodobacter capsulatus, but the approach is applicable to photobiological systems that are to be operated under outdoor conditions with significant cooling demands.

  3. 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.

  4. Tubular aggregates of cyclic oligothiophenes. A theoretical study.

    PubMed

    Flores, Paola; Guadarrama, Patricia; Ramos, Estrella; Fomine, Serguei

    2008-05-01

    The geometries of neutral, mono-, and dioxidized tubular aggregates of cyclo[8]thiophenes containing up to 5 repeating units were fully optimized at the MPWB1K/3-21G* level of theory. Calculated interplane distances between macrocycles were found to be close to 3.1 A for neutral and charged aggregates. The binding energies between macrocycles in neutral intermediates were in the range of 40-45 kcal/mol, increasing for monocations and dropping strongly for dicationic species due to electrostatic repulsion between polarons. It was established that there exists a noticeable interaction between pi-orbitals of individual macrocycles in tubular aggregates as follows from decreasing of the band gap with a number of repeating units in aggregates and the polaron delocalization toward tube axes in oxidized species. A polaron pair is the most stable dicationic state for all studied molecules according to the calculations. A singlet polaron pair is more stable than a triplet one. The energy difference between singlet and triplet states is growing smaller with the size of the system, becoming zero for the pentamer corresponding to a completely dissociated bipolaron.

  5. 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.

  6. Tubular woven narrow fabrics for replacement of cruciate ligaments.

    PubMed

    Gloy, Yves-Simon; Loehrer, M; Lang, B; Rongen, L; Gries, T; Jockenhoevel, S

    2013-09-01

    The human knee is one of the most frequently injured joints. More than half of these injuries are related to a failure of the anterior cruciate ligament. Current treatments (allogeneic and autologous) bear several disadvantages which can be overcome through the use of synthetic structures. Within the scope of this paper the potential of tubular woven fabrics for the use as artificial ligaments has been evaluated. Twelve fabrics made of polyethylene terephthalate and polytetrafluoroethylene were produced using shuttle weaving technology. Mechanical and biological properties of the fabrics were assessed using static tensile testing and cytotoxicity assays. The results obtained within this study show that woven tubular fabrics can be potentially used as artificial ligament structures as they can provide the desired medical and mechanical properties for cruciate ligament replacements. Through the choice of material and weaving parameters the fabrics' tensile properties can imitate the stress-strain characteristic of the human cruciate ligament. Further assessments in terms of cyclic loading behavior and abrasion resistance of the material are needed to evaluate the success in long term implantation.

  7. 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.

  8. 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

  9. Negative Stains Containing Trehalose: Application to Tubular and Filamentous Structures

    NASA Astrophysics Data System (ADS)

    Harris, J. Robin; Gerber, Max; Gebauer, Wolfgang; Wernicke, Wolfgang; Markl, Jürgen

    1996-02-01

    Several examples are presented that show the successful application of uranyl acetate and ammonium molybdate negative staining in the presence of trehalose for TEM studies of filamentous and tubular structures. The principal benefit to be gained from the inclusion of trehalose stems from the considerably reduced flattening of the large tubular structures and the greater orientational freedom of single molecules due to an increased depth of the negative stain in the presence of trehalose. Trehalose is likely to provide considerable protection to protein molecules and their assemblies during the drying of negatively stained specimens. Some reduction in the excessive density imparted by uranyl acetate around large assemblies is also achieved. Nevertheless, in the presence of 1% (w/v) trehalose, it is desirable to increase the concentration of negative stain to 5% (w/v) for ammonium molybdate and to 4% for uranyl acetate to produce satisfactory image contrast. In general, the ammonium molybdate-trehalose negative stain is more satisfactory than the uranyl acetate-trehalose combination, because of the greater electron beam sensitivity of the uranyl negative stain. Reassembled taxol-stabilized pig brain microtubules, together with collagen fibrils, sperm tails, helical filaments, and reassociated hemocyanin (KLH2), all from the giant keyhole limpet Megathura crenulata, have been studied by negative staining in the presence of trehalose. In all cases satisfactory TEM imaging conditions were readily obtained on the specimens, as long as regions of excessively deep stain were avoided.

  10. Impregnation of tubular self-assemblies into dextran hydrogels.

    PubMed

    Sun, Guoming; Chu, Chih-Chang

    2010-02-16

    Amine groups are the building units of proteins. The incorporation of amine groups into polyethylene glycol diacrylate (PEGDA) hydrogel through dextran-allyl isocyanate-ethylamine (Dex-AE) enhances sustained protein release by introducing effective interactions. To investigate such an interaction effect and to improve protein release, we impregnated self-assembled tubular structures from dextran-bromoethylamine (Dex-BH) and dextran-chloroacetic acid (Dex-CA) into Dex-AE/PEGDA hydrogel. The morphology data obtained from scanning electron microscopy (SEM) reveal that pure PEGDA hydrogel had no effect on the distribution of the self-assembled tubules; the introduction of Dex-AE brought about the dispersion of these tubules, and an increase in Dex-AE content led to more evenly distributed structures. Moreover, the implantation of the self-assembled tubules had no distinct effect on the swelling capacity of the hybrid self-assembly embedded hydrogels. The in vitro albumin release study was carried out in a pH 7.4 buffer solution; the results show that the implantation of the self-assembly into the hydrogels reduced the burst release and prolonged the protein release time. These findings demonstrate that the impregnation of tubular self-assembly into hydrogel makes the hybrid hydrogel an excellent protein delivery system.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Intraductal tubular neoplasms of the pancreas: an overview.

    PubMed

    Chelliah, Adeline; Kalimuthu, Sangeetha; Chetty, Runjan

    2016-10-01

    Intraductal lesions of the pancreas are an uncommon but increasingly recognized group of entities mainly because of advances in imaging technology. In the past, precise categorization and understanding of true pancreatic intraduct neoplasms were hampered not only by their relative rarity but also because of the plethora of terminology and criteria used in nomenclature and diagnosis. Although significant progress has been made in the characterization of some of these lesions, as exemplified by intraductal papillary mucinous neoplasms, understanding of the rare intraductal tubular adenoma (ITA) and intraduct tubular carcinoma (ITC) continues to evolve. By definition, these are a group of intraductal, radiologically detectable neoplasms that can progress to or be associated with invasive adenocarcinoma and, as such, are precursor lesions to pancreatic ductal adenocarcinoma. Their often shared clinical and radiological features make precise histological diagnosis essential for appropriate management and optimal outcome. We provide an overview of these neoplasms and highlight recent developments in the understanding of ITA and ITC which have led to ITA being considered a variant of gastric-type intraductal papillary mucinous neoplasms and ITC being encompassed within the intraductal tubulopapillary neoplasm category. We also emphasize the distinguishing histological features to aid diagnosis of these rare lesions.

  16. 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.

  17. 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.

  18. Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

    SciTech Connect

    Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

    2009-11-15

    Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

  19. Low molecular weight fucoidan protects renal tubular cells from injury induced by albumin overload

    PubMed Central

    Jia, Yingli; Sun, Yi; Weng, Lin; Li, Yingjie; Zhang, Quanbin; Zhou, Hong; Yang, Baoxue

    2016-01-01

    Albuminuria is a causative and aggravating factor for progressive renal damage in chronic kidney disease (CKD). The aim of this study was to determine if low molecular weight fucoidan (LMWF) could protect renal function and tubular cells from albumin overload caused injury. Treatment with 10 mg/g bovine serum albumin caused renal dysfunction, morphological changes, and overexpression of inflammation and fibrosis associated proteins in 129S2/Sv mice. LMWF (100 mg/kg) protected against kidney injury and renal dysfunction with decreased blood creatinine by 34% and urea nitrogen by 25%, increased creatinine clearance by 48%, and decreased significantly urinary albumin concentration. In vitro proximal tubule epithelial cell (NRK-52E) model showed that LMWF dose-dependently inhibited overexpression of proinflammatory and profibrotic factors, oxidative stress and apoptosis caused by albumin overload. These experimental results indicate that LMWF protects against albumin overload caused renal injury by inhibiting inflammation, fibrosis, oxidative stress and apoptosis, which suggests that LMWF could be a promising candidate drug for preventing CKD. PMID:27545472

  20. Tubular and glomerular kidney effects in the Chinese general population with low environmental cadmium exposure.

    PubMed

    Wang, Dongyue; Sun, Hong; Wu, Ye; Zhou, Zhengyuan; Ding, Zhen; Chen, Xiaodong; Xu, Yan

    2016-03-01

    Cadmium (Cd), a well-known nephrotoxic agent, has received a great deal of attention from the Chinese public because of reports of its presence in rice. But very few studies have assessed the renal risk of Cd exposure in children. In this cross-sectional study, we aimed to determine whether biologic measures of Cd exposure were associated with biomarkers of early kidney damage in children, adolescents and adults. A total of 1235 subjects (2-86.8 years old) participated in this study and provided samples of blood and urine. As a result, the median urinary Cd level was 0.38 μg g(-1) creatinine in adult men and 0.42 μg g(-1) creatinine in adult women, similar to reference values observed in the United States (median: 0.32-0.40 μg L(-1) in adults). Multiple linear regressions showed Cd in urine to be significantly positively associated with effects on renal tubule biomarkers (as indicated by increased levels of N-acetyl-β-D-glucosaminidase and β2-microglobulin) after adjusting for age, body mass index, blood lead, and urinary density, in all age groups including children. We also found positive associations between blood Cd and renal tubule biomarkers in children. In conclusion, adverse tubular renal effects might have occurred at the current low Cd levels in the study population, including children. These findings are particularly relevant assessing health risks associated with low environmental exposures to Cd.

  1. Pancreatic pseudocyst after acute organophosphate poisoning.

    PubMed

    Kawabe, Ken; Ito, Tetsuhide; Arita, Yoshiyuki; Sadamoto, Yojiro; Harada, Naohiko; Yamaguchi, Koji; Tanaka, Masao; Nakano, Itsuro; Nawata, Hajime; Takayanagi, Ryoichi

    2006-04-01

    Acute organophosphate poisoning (OP) shows several severe clinical symptoms due to its strong blocking effect on cholinesterase. Acute pancreatitis is one of the complications associated with acute OP, but this association still may not be widely recognized. We report here the case of a 73-year-old man who had repeated abdominal pain during and after the treatment of acute OP. Hyperamylasemia and a 7-cm pseudocyst in the pancreatic tail were noted on investigations. We diagnosed pancreatic pseudocyst that likely was secondary to an episode of acute pancreatitis following acute OP. He was initially treated with a long-term intravenous hyperalimentation, protease inhibitors and octerotide, but eventually required surgical intervention, a cystgastrostomy. Acute pancreatitis and hyperamylasemia are known to be possible complications of acute OP. It is necessary to examine and assess pancreatic damage in patients with acute OP.

  2. Differential role of hydrogen peroxide and organic hydroperoxides in augmenting ferric nitrilotriacetate (Fe-NTA)-mediated DNA damage: implications for carcinogenesis.

    PubMed

    Iqbal, Mohammad; Sharma, Som Datta; Mizote, Akiko; Fujisawa, Masayoshi; Okada, Shigeru

    2003-01-01

    An iron chelate, ferric nitrilotriacetate (Fe-NTA), is a potent nephrotoxic agent, and induces acute and subacute renal proximal tubular necrosis, a consequence of the Fenton-like reaction that eventually leads to a high incidence of renal adenocarcinoma in rodents. In order to examine the possible mechanism for carcinogenic activity, we investigated the DNA damage with Fe-NTA in the presence of various peroxides/organic hydroperoxides. S1 nuclease hydrolysis and deoxyribose degradation assays were performed. Incubation of calf thymus DNA with ferric nitrilotriacetate (0.1 mM) in the presence of peroxides/organic hydroperoxides at a final concentration of 40 mM of each in phosphate buffer (0.1 M, pH 7.4) augmented DNA damage severalfold as compared to the damage caused by individual treatments. Fe-NTA in the presence of hydrogen peroxide caused DNA single-strand breaks and damage to its deoxyribose sugar moiety as measured, respectively, by S1 nuclease hydrolysis and deoxyribose degradation using calf thymus DNA. However, only deoxyribose degradation could be recorded in the presence of other peroxide/organic hydroperoxides. No DNA single-strand break was observed by this treatment. The observed differences in DNA damage by hydrogen peroxide and organic hydroperoxides/peroxide have been ascribed to the differential reactivity of DNA with hydroxyl and alkoxy/aryloxy free radicals produced, respectively, from these inorganic and organic peroxides. These studies suggest that Fe-NTA not only mediated the production of reactive oxygen species, but also catalysed the decomposition of these peroxides and organic hydroperoxides, which may cause a clastogenic change in DNA. This reactivity enhances the clastogenic activity in DNA. These changes in the DNA structure may ultimately be responsible, at least in part, for the induction of carcinogenesis in Fe-NTA-exposed animals.

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

    PubMed

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

    2013-02-15

    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 (5mg/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 (2mg/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.

  4. Effects of shiga toxin 2 on cellular regeneration mechanisms in primary and three-dimensional cultures of human renal tubular epithelial cells.

    PubMed

    Márquez, Laura B; Araoz, Alicia; Repetto, Horacio A; Ibarra, Fernando R; Silberstein, Claudia

    2016-10-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) causes post-diarrheal Hemolytic Uremic Syndrome (HUS), which is one of the most common causes of acute renal failure in children in Argentine. The aim of the present work was to study the effects of Shiga toxin type 2 (Stx2) on regenerative mechanisms of primary cultures of human cortical renal tubular epithelial cells (HRTEC) and three-dimensional (3D) cultures of HRTEC. Primary cultures of HRTEC were able to develop tubular structures when grown in matrigel, which showed epithelial cells surrounding a central lumen resembling the original renal tubules. Exposure to Stx2 inhibited tubulogenesis in 3D-HRTEC cultures. Moreover, a significant increase in apoptosis, and decrease in cell proliferation was observed in tubular structures of 3D-HRTEC exposed to Stx2. A significant reduction in cell migration and vimentin expression levels was observed in HRTEC primary cultures exposed to Stx2, demonstrating that the holotoxin affected HRTEC dedifferentiation. Furthermore, a decreased number of cells expressing CD133 progenitor marker was found in HRTEC cultures treated with Stx2. The CD133 positive cells also expressed the Stx receptor globotriaosylceramide, which may explain their sensitivity to Stx2. In conclusion, Stx2 affects the regenerative processes of human renal tubular epithelial cells in vitro, by inhibiting cell dedifferentiation mechanisms, as well as tubules restoration. The development of 3D-HRTEC cultures that resemble original human renal proximal tubules is a novel in vitro model to study renal epithelial repair mechanisms after injury.

  5. 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.

  6. 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

    ... 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, 2012... Turkey and several other countries.\\1\\ The CVD investigation and the AD investigations cover the...

  7. Tubular Carcinoma of the Breast: Advantages and Limitations of Breast Tomosynthesis

    PubMed Central

    Rocha, Ana; Reis, Alcinda

    2016-01-01

    Tubular carcinoma of the breast is a rare variant of invasive ductal carcinoma. We report a case of 42-year-old asymptomatic female with a histopathological proven multifocal tubular carcinoma, studied by mammography, Tomosynthesis, Ultrasound, and Magnetic Resonance. Herein, we discuss the advantages and limitations of Tomosynthesis, an emerging imaging technique, in this particular case. PMID:28116205

  8. Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.

    PubMed

    Sharoar, M G; Shi, Q; Ge, Y; He, W; Hu, X; Perry, G; Zhu, X; Yan, R

    2016-09-01

    Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains. Functionally, abnormally clustered tubular ER induces enhanced mitochondrial fission in the early stages of DN formation and eventual mitochondrial degeneration at later stages. Furthermore, such DNs are abrogated when RTN3 is ablated in aging and AD mouse models. Hence, abnormally clustered tubular ER can be pathogenic in brain regions: disrupting mitochondrial integrity, inducing DNs formation and impairing cognitive function in AD and aging brains.

  9. Pathophysiology of acute pancreatitis.

    PubMed

    Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi

    2005-01-01

    Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.

  10. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.

    PubMed

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Zhang, Zhi-Hui; Wang, Hua; Zhao, Hui; Yu, De-Xin; Xu, De-Xiang

    2015-12-22

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury.

  11. Cultivation of shear stress sensitive and tolerant microalgal species in a tubular photobioreactor equipped with a centrifugal pump.

    PubMed

    Michels, Michiel H A; van der Goot, Atze Jan; Vermuë, Marian H; Wijffels, René H

    The tolerance to shear stress of Tetraselmis suecica, Isochrysis galbana, Skeletonema costatum, and Chaetoceros muelleri was determined in shear cylinders. The shear tolerance of the microalgae species strongly depends on the strain. I. galbana, S. costatum, and C. muelleri exposed to shear stress between 1.2 and 5.4 Pa resulted in severe cell damage. T. suecica is not sensitive to stresses up to 80 Pa. The possibility to grow these algae in a tubular photobioreactor (PBR) using a centrifugal pump for recirculation of the algae suspension was studied. The shear stresses imposed on the algae in the circulation tubes and at the pressure side of the pump were 0.57 and 1.82 Pa, respectively. The shear stress tolerant T. suecica was successfully cultivated in the PBR. Growth of I. galbana, S. costatum, and C. muelleri in the tubular PBR was not observed, not even at the lowest pumping speed. For the latter shear sensitive strains, the encountered shear stress levels were in the order of magnitude of the determined maximum shear tolerance of the algae. An equation was used to simulate the effect of possible damage of microalgae caused by passages through local high shear zones in centrifugal pumps on the total algae culture in the PBR. This simulation shows that a culture of shear stress sensitive species is bound to collapse after only limited number of passages, confirming the importance of considering shear stress as a process parameter in future design of closed PBRs for microalgal cultivation.

  12. Characterization and preparation of bio-tubular scaffolds for fabricating artificial vascular grafts by combining electrospinning and a 3D printing system.

    PubMed

    Lee, Sang Jin; Heo, Dong Nyoung; Park, Ji Sun; Kwon, Seong Keun; Lee, Jin Ho; Lee, Jun Hee; Kim, Wan Doo; Kwon, Il Keun; Park, Su A

    2015-02-07

    The last decade has seen artificial blood vessels composed of natural polymer nanofibers grafted into human bodies to facilitate the recovery of damaged blood vessels. However, electrospun nanofibers (ENs) of biocompatible materials such as chitosan (CTS) suffer from poor mechanical properties. This study describes the design and fabrication of artificial blood vessels composed of a blend of CTS and PCL ENs and coated with PCL strands using rapid prototyping technology. The resulting tubular vessels exhibited excellent mechanical properties and showed that this process may be useful for vascular reconstruction.

  13. Damage assessment in systemic vasculitis.

    PubMed

    Silveira, Luis H

    2008-12-01

    Systemic vasculitides were initially reported as acute, progressive, severe, and life-threatening diseases. The introduction of glucocorticoids and cyclophosphamide for the treatment of vasculitis improved survival dramatically, but morbidity has remained high. Damage develops as a consequence of recurrent or persistent active vasculitis or its treatment. It is defined as the accumulation of nonhealing scars that are unlikely to respond to immunosuppressive therapy. Damage assessment is essential in systemic vasculitis because it may facilitate patient stratification in clinical trials and possibly in clinical practice. Moreover, it may avoid unnecessary use of immunosuppressive therapy. The Vasculitis Damage Index, developed and validated in 1997, has been very useful in solving many matters in systemic vasculitis and is currently the only validated damage-assessment tool available. However, the vasculitis community has recognized that there is a growing need to improve the evaluation of damage in vasculitis. The development of a Combined Damage Assessment index, which would permit a more appropriate and standardized approach to disease assessment applicable to systemic vasculitis, has been proposed.

  14. Pathophysiology of ischaemic acute kidney injury.

    PubMed

    Kanagasundaram, Nigel Suren

    2015-03-01

    Acute kidney injury is common, dangerous and costly, affecting around one in five patients emergency admissions to hospital. Although survival decreases as disease worsens, it is now apparent that even modest degrees of dysfunction are not only associated with higher mortality but are an independent risk factor for death. This review focuses on the pathophysiology of acute kidney injury secondary to ischaemia - its commonest aetiology. The haemodynamic disturbances, endothelial injury, epithelial cell injury and immunological mechanisms underpinning its initiation and extension will be discussed along with the considerable and complex interplay between these factors that lead to an intense, pro-inflammatory state. Mechanisms of tubular recovery will be discussed but also the pathophysiology of abnormal repair with its direct consequences for long-term renal function. Finally, the concept of 'organ cross-talk' will be introduced as a potential explanation for the higher mortality observed with acute kidney injury that might be deemed modest in conventional biochemical terms.

  15. Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury

    PubMed Central

    Markó, Lajos; Szijártó, István A.; Filipovic, Milos R.; Kaßmann, Mario; Balogh, András; Park, Joon-Keun; Przybyl, Lukasz; N’diaye, Gabriele; Krämer, Stephanie; Anders, Juliane; Ishii, Isao; Müller, Dominik N.; Gollasch, Maik

    2016-01-01

    Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth−/−) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth−/− and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth−/− mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth−/− mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection. PMID:27273292

  16. 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

    2016-01-11

    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.

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

    PubMed Central

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

    2016-01-01

    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

  18. Evaluation of composite flattened tubular specimen. [fatigue tests

    NASA Technical Reports Server (NTRS)

    Liber, T.; Daniel, I. M.

    1978-01-01

    Flattened tubular specimens of graphite/epoxy, S-glass/epoxy, Kevlar-49/epoxy, and graphite/S-glass/epoxy hybrid materials were evaluated under static and cyclic uniaxial tensile loading and compared directly with flat coupon data of the same materials generated under corresponding loading conditions. Additional development for the refinement of the flattened specimen configuration and fabrication was required. Statically tested graphite/epoxy, S-glass/epoxy, and Kevlar 49/epoxy flattened tube specimens exhibit somewhat higher average strengths than their corresponding flat coupons. Flattened tube specimens of the graphite/S-glass/epoxy hybrid and the graphite/epoxy flattened tube specimens failed in parasitic modes with consequential lower strength than the corresponding flat coupons. Fatigue tested flattened tube specimens failed in parasitic modes resulting in lower fatigue strengths than the corresponding flat coupons.

  19. Clinical approach to renal tubular acidosis in adult patients.

    PubMed

    Reddy, P

    2011-03-01

    Renal tubular acidosis (RTA) is a group of disorders observed in patients with normal anion gap metabolic acidosis. There are three major forms of RTA: A proximal (type II) RTA and two types of distal RTAs (type I and type IV). Proximal (type II) RTA originates from the inability to reabsorb bicarbonate normally in the proximal tubule. Type I RTA is associated with inability to excrete the daily acid load and may present with hyperkalaemia or hypokalaemia. The most prominent abnormality in type IV RTA is hyperkalaemia caused by hypoaldosteronism. This article extensively reviews the mechanism of hydrogen ion generation from metabolism of normal diet and various forms of RTA leading to disruptions of normal acid-base handling by the kidneys.

  20. Mass and heat transfer model of Tubular Solar Still

    SciTech Connect

    Ahsan, Amimul; Fukuhara, Teruyuki

    2010-07-15

    In this paper, a new mass and heat transfer model of a Tubular Solar Still (TSS) was proposed incorporating various mass and heat transfer coefficients taking account of the humid air properties inside the still. The heat balance of the humid air and the mass balance of the water vapor in the humid air were formulized for the first time. As a result, the proposed model enabled to calculate the diurnal variations of the temperature, water vapor density and relative humidity of the humid air, and to predict the hourly condensation flux besides the temperatures of the water, cover and trough, and the hourly evaporation flux. The validity of the proposed model was verified using the field experimental results carried out in Fukui, Japan and Muscat, Oman in 2008. The diurnal variations of the calculated temperatures and water vapor densities had a good agreement with the observed ones. Furthermore, the proposed model can predict the daily and hourly production flux precisely. (author)

  1. Scavenging energy from human motion with tubular dielectric polymer

    NASA Astrophysics Data System (ADS)

    Jean-Mistral, Claire; Basrour, Skandar

    2010-04-01

    Scavenging energy from human motion is a challenge to supply low consumption systems for sport or medical applications. A promising solution is to use electroactive polymers and especially dielectric polymers to scavenge mechanical energy during walk. In this paper, we present a tubular dielectric generator which is the first step toward an integration of these structures into textiles. For a 10cm length and under a strain of 100%, the structure is able to scavenge 1.5μJ for a poling voltage of 200V and up to 40μJ for a poling voltage of 1000V. A 30cm length structure is finally compared to our previous planar structure, and the power management module for those structures is discussed.

  2. Guided growth by a stainless-steel tubular plate.

    PubMed

    Lin, Tung-Yi; Kao, Hsuan-Kai; Li, Wei-Chun; Yang, Wen-E; Chang, Chia-Hsieh

    2013-07-01

    Guided growth using titanium tension band plates is an advancement in the correction of angular deformity. We applied two-hole stainless-steel one-third tubular plates for the same purpose. There were 14 deformities around the knees in eight children, mean age 10.8 years at operation. The success rate was 92.9% (13/14). The average correction rate per month was 0.59° in the femur and 0.65° in the tibia. No premature physeal arrest, overcorrection, or rebound phenomenon was observed. A stainless-steel plate is a safe and effective option for guided growth surgery in countries where only stainless-steel plates are available.

  3. Transient response of a concentric evacuated tubular solar collector

    NASA Astrophysics Data System (ADS)

    Al-Khalil, Kamel M.; Jakubowski, Gerald S.; Springman, Richard A.

    The transient and the steady state performances of an evacuated coaxial tubular solar collector were investigated. A purely implicit central finite differencing numerical technique was used to determine the time-varying temperature distributions in the collector components as well as the fluid exit temperature. Experimental indoor transient tests were conducted in which step inputs of insolation were used. Close agreeement between the experimental and the theoretical results was obtained. The computer model was found to be useful to carry out a complete parametric study. The latter showed that the fluid flow rate had the largest effect on the performance of the collector tube. Lower flow rates resulted in lower efficiencies and longer response times.

  4. Scalable Approach for Extrusion and Perfusion of Tubular, Heterotypic Biomaterials

    NASA Astrophysics Data System (ADS)

    Jeronimo, Mark David

    Soft material tubes are critical in the vasculature of mammalian tissues, forming networks of blood vessels and airways. Homogeneous and heterogeneous hydrogel tubes were extruded in a one-step process using a three layer microfluidic device. Co-axial cylindrical flow of crosslinking solutions and an alginate matrix is generated by a radial arrangement of microfluidic channels at the device's vertical extrusion outlet. The flow is confined and begins a sol-gel transition immediately as it extrudes at velocities upwards of 4 mm/s. This approach allows for predictive control over the dimensions of the rapidly formed tubular structures for outer diameters from 600 microm to 3 mm. A second microfluidic device hosts tube segments for controlled perfusion and pressurization using a reversible vacuum seal. On-chip tube deflection is observed and modeled as a measure of material compliance and circumferential elasticity. I anticipate applications of these devices for perfusion cell culture of cell-laden hydrogel tubes.

  5. [Diagnostic difficulties in a case of constricted tubular visual field].

    PubMed

    Dogaru, Oana-Mihaela; Rusu, Monica; Hâncu, Dacia; Horvath, Kárin

    2013-01-01

    In the paper below we present the clinical case of a 48 year old female with various symptoms associated with functional visual disturbance -constricted tubular visual fields, wich lasts from 6 years; the extensive clinical and paraclinical ophthalmological investigations ruled out the presence of an organic disorder. In the present, we suspect a diagnosis of hysteria, still uncertain, wich represented over time a big challenge in psychology and ophthalmology. The mechanisms and reasons for hysteria are still not clear and it could represent a fascinating research theme. The tunnel, spiral or star-shaped visual fields are specific findings in hysteria for patients who present visual disturbance. The question of whether or not a patient with hysterical visual impairment can or cannot "see" is still unresolved.

  6. Numerical Simulation of Tubular Pumping Systems with Different Regulation Methods

    NASA Astrophysics Data System (ADS)

    Zhu, Honggeng; Zhang, Rentian; Deng, Dongsheng; Feng, Xusong; Yao, Linbi

    2010-06-01

    Since the flow in tubular pumping systems is basically along axial direction and passes symmetrically through the impeller, most satisfying the basic hypotheses in the design of impeller and having higher pumping system efficiency in comparison with vertical pumping system, they are being widely applied to low-head pumping engineering. In a pumping station, the fluctuation of water levels in the sump and discharge pool is most common and at most time the pumping system runs under off-design conditions. Hence, the operation of pump has to be flexibly regulated to meet the needs of flow rates, and the selection of regulation method is as important as that of pump to reduce operation cost and achieve economic operation. In this paper, the three dimensional time-averaged Navier-Stokes equations are closed by RNG κ-ɛ turbulent model, and two tubular pumping systems with different regulation methods, equipped with the same pump model but with different designed system structures, are numerically simulated respectively to predict the pumping system performances and analyze the influence of regulation device and help designers make final decision in the selection of design schemes. The computed results indicate that the pumping system with blade-adjusting device needs longer suction box, and the increased hydraulic loss will lower the pumping system efficiency in the order of 1.5%. The pumping system with permanent magnet motor, by means of variable speed regulation, obtains higher system efficiency partly for shorter suction box and partly for different structure design. Nowadays, the varied speed regulation is realized by varied frequency device, the energy consumption of which is about 3˜4% of output power of the motor. Hence, when the efficiency of variable frequency device is considered, the total pumping system efficiency will probably be lower.

  7. Tubular Scaffold with Shape Recovery Effect for Cell Guide Applications

    PubMed Central

    Hossain, Kazi M. Zakir; Zhu, Chenkai; Felfel, Reda M.; Sharmin, Nusrat; Ahmed, Ifty

    2015-01-01

    Tubular scaffolds with aligned polylactic acid (PLA) fibres were fabricated for cell guide applications by immersing rolled PLA fibre mats into a polyvinyl acetate (PVAc) solution to bind the mats. The PVAc solution was also mixed with up to 30 wt % β-tricalcium phosphate (β-TCP) content. Cross-sectional images of the scaffold materials obtained via scanning electron microscopy (SEM) revealed the aligned fibre morphology along with a significant number of voids in between the bundles of fibres. The addition of β-TCP into the scaffolds played an important role in increasing the void content from 17.1% to 25.3% for the 30 wt % β-TCP loading, which was measured via micro-CT (µCT) analysis. Furthermore, µCT analyses revealed the distribution of aggregated β-TCP particles in between the various PLA fibre layers of the scaffold. The compressive modulus properties of the scaffolds increased from 66 MPa to 83 MPa and the compressive strength properties decreased from 67 MPa to 41 MPa for the 30 wt % β-TCP content scaffold. The scaffolds produced were observed to change into a soft and flexible form which demonstrated shape recovery properties after immersion in phosphate buffered saline (PBS) media at 37 °C for 24 h. The cytocompatibility studies (using MG-63 human osteosarcoma cell line) revealed preferential cell proliferation along the longitudinal direction of the fibres as compared to the control tissue culture plastic. The manufacturing process highlighted above reveals a simple process for inducing controlled cell alignment and varying porosity features within tubular scaffolds for potential tissue engineering applications. PMID:26184328

  8. Tubular Scaffold with Shape Recovery Effect for Cell Guide Applications.

    PubMed

    Hossain, Kazi M Zakir; Zhu, Chenkai; Felfel, Reda M; Sharmin, Nusrat; Ahmed, Ifty

    2015-07-10

    Tubular scaffolds with aligned polylactic acid (PLA) fibres were fabricated for cell guide applications by immersing rolled PLA fibre mats into a polyvinyl acetate (PVAc) solution to bind the mats. The PVAc solution was also mixed with up to 30 wt % β-tricalcium phosphate (β-TCP) content. Cross-sectional images of the scaffold materials obtained via scanning electron microscopy (SEM) revealed the aligned fibre morphology along with a significant number of voids in between the bundles of fibres. The addition of β-TCP into the scaffolds played an important role in increasing the void content from 17.1% to 25.3% for the 30 wt % β-TCP loading, which was measured via micro-CT (µCT) analysis. Furthermore, µCT analyses revealed the distribution of aggregated β-TCP particles in between the various PLA fibre layers of the scaffold. The compressive modulus properties of the scaffolds increased from 66 MPa to 83 MPa and the compressive strength properties decreased from 67 MPa to 41 MPa for the 30 wt % β-TCP content scaffold. The scaffolds produced were observed to change into a soft and flexible form which demonstrated shape recovery properties after immersion in phosphate buffered saline (PBS) media at 37 °C for 24 h. The cytocompatibility studies (using MG-63 human osteosarcoma cell line) revealed preferential cell proliferation along the longitudinal direction of the fibres as compared to the control tissue culture plastic. The manufacturing process highlighted above reveals a simple process for inducing controlled cell alignment and varying porosity features within tubular scaffolds for potential tissue engineering applications.

  9. On milling of thin-wall conical and tubular workpieces

    NASA Astrophysics Data System (ADS)

    Tsai, Mu-Ping; Tsai, Nan-Chyuan; Yeh, Cheng-Wei

    2016-05-01

    Thin-wall tubular-geometry workpieces have been widely applied in aircraft and medical industries. However, due to the special geometry of this kind of workpieces and induced poor machinability, the desired accuracy of machining tends to be greatly degraded, no matter what type of metal-cutting task such as milling, drilling or turning is undertaken. Though numerous research reports are available that the tool path can be planned on the basis of preset surface profile before actual milling operation is performed, it is still difficult to predict the real-time surface profile errors for peripheral milling of thin-wall tubular workpieces. Instead of relying on tool path planning, this research is focused on how to real-time formulate the appropriate applied cutting torque via feedback of spindle motor current. On the other hand, a few suitable cutting conditions which are able to prevent potential break/crack of thin-wall workpieces and enhance productivity but almost retain the same cutting quality is proposed in this research. To achieve this goal, estimated surface profile error on machined parts due to deflections caused by both tool and workpiece is studied at first. Traditionally, by adjusting cutting parameters such as feed rate or cut depth, the deflection of tool or workpiece can be expected not to exceed the specified limit. Instead, an effective feedback control loop is proposed by this work for applying real-time appropriate applied cutting torque to prevent potential break/crack of the thin-wall conical workpieces. The torque estimation approach by spindle motor current feedback and the corresponding fuzzy logic controller are employed. Compared with constant cutting torque during milling operation in tradition manner, it is observed that the time consumption of milling cycle by aid of the aforesaid fuzzy logic controller is greatly shortened while the resulted cutting accuracy upon finish of workpiece can be almost retained.

  10. Acute viral myocarditis

    PubMed Central

    Dennert, Robert; Crijns, Harry J.; Heymans, Stephane

    2008-01-01

    Acute myocarditis is one of the most challenging diagnosis in cardiology. At present, no diagnostic gold standard is generally accepted, due to the insensitivity of traditional diagnostic tests. This leads to the need for new diagnostic approaches, which resulted in the emergence of new molecular tests and a more detailed immunohistochemical analysis of endomyocardial biopsies. Recent findings using these new diagnostic tests resulted in increased interest in inflammatory cardiomyopathies and a better understanding of its pathophysiology, the recognition in overlap of virus-mediated damage, inflammation, and autoimmune dysregulation. Novel results also pointed towards a broader spectrum of viral genomes responsible for acute myocarditis, indicating a shift of enterovirus and adenovirus to parvovirus B19 and human herpes virus 6. The present review proposes a general diagnostic approach, focuses on the viral aetiology and associated autoimmune processes, and reviews treatment options for patients with acute viral myocarditis. PMID:18617482

  11. Genomic damage in chronic renal failure--potential therapeutic interventions.

    PubMed

    Stopper, Helga; Schupp, Nicole; Klassen, André; Sebekova, Katarina; Heidland, August

    2005-01-01

    In end-stage renal failure, genomic damage is enhanced. This has been shown both in the predialysis and dialysis phase by various biomarkers, such as micronuclei frequency and single cell gel electrophoresis in lymphocytes as well as with 8-hydroxy-2'-deoxyguanosine in leukocytes. There are also data about mitochondrial DNA deletions and chromosomal abnormalities. Genomic damage may be induced by a multitude of toxic factors and mutagens, in particular via enhanced generation of reactive oxygen species. In in vitro studies, incubation of tubular cells with various AGEs (carboxymethyllysine-BSA, AGE-BSA, and methylglyoxal-BSA) and angiotensin II resulted in a marked DNA damage. Coincubation with various antioxidants as well as the angiotensin II receptor blocker, candesartan, suppressed the toxic action. Moreover, an improved uremic state by daily hemodialysis ameliorated the genomic damage in lymphocytes, as compared to patients on conventional hemodialysis.

  12. 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.

  13. Isoniazid-induced seizures with secondary rhabdomyolysis and associated acute renal failure in a dog.

    PubMed

    Haburjak, J J; Spangler, W L

    2002-04-01

    Isoniazid-induced seizures resulted in rhabdomyolysis and associated acute renal tubular necrosis in a dog. Rhabdomyolysis and myoglobinuric renal failure, although recognised in the dog, are reported infrequently as a consequence of seizures. The clinical presentation of isoniazid toxicity in a dog is described.

  14. Nephro-protective effect of a novel formulation of unopened coconut inflorescence sap powder on gentamicin induced renal damage by modulating oxidative stress and inflammatory markers.

    PubMed

    Jose, Svenia P; S, Asha; Im, Krishnakumar; M, Ratheesh; Santhosh, Savitha; S, Sandya; B, Girish Kumar; C, Pramod

    2017-01-01

    Fresh oyster white translucent sap obtained from the tender unopened inflorescence of coconut trees (Cocos nucifera) is identified to have great health benefits. Drug induced Nephrotoxicity is one of the major causes of renal damage in present generation. As a therapeutic agent, gentamicin imparts direct toxicity to kidney, resulting in acute tubular necrosis, glomerular and tubulointerstitial injury, haemodynamically mediated damage and obstructive nephropathy.There exists an increasing demand for safe and natural agents for the treatment and/or preventionofchronic nephrotoxicity and pathogenesis of kidney diseases. Our study shows the nephro protective/curing effect of a novel powder formulation of micronutrient enriched, unfermented coconut flower sap (CSP). The study was performed on adult male Wistar rats. The animals were grouped into three and treated separately with vehicle, gentamicin and gentamicin+CSP for 16days. Initially, gentamicin treatment significantly (p<0.05)reduced thelevels of antioxidant enzymes (SOD, CAT, GPx) and GSH and increased (p<0.05) the levels of creatinine, uric acid, urea, inflammatory markers (nitrite, IL-6, TNF- α, iNOS) and lipid peroxidation. Supplementation of coconut flower sap powder showed significant (p<0.05) reversal of all these biochemical parameters indicating an effective inhibition of the pathogenesis of nephrotoxicity and kidney disease.