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  1. 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 ...

  2. NiCl2-down-regulated antioxidant enzyme mRNA expression causes oxidative damage in the broiler(')s kidney.

    PubMed

    Guo, Hongrui; Wu, Bangyuan; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Deng, Jie; Yin, Shuang; Li, Jian; Tang, Kun

    2014-12-01

    The kidney serves as a major organ of nickel (Ni) excretion and is a target organ for acute Ni toxicity due to Ni accumulation. There are no studies on the Ni or Ni compound-regulated antioxidant enzyme mRNA expression in animals and human beings at present. This study was conducted to investigate the pathway of nickel chloride (NiCl2)-caused renal oxidative damage by the methods of biochemistry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Two hundred and eighty one-day-old broilers were randomly divided into four groups and fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg of NiCl2 for 42 days. Dietary NiCl2 elevated the malondialdehyde (MDA), nitric oxide (NO), 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents, and reduced the ability to inhibit hydroxy radical in the NiCl2-treated groups. Also, the renal inducible nitric oxide synthase (iNOS) activity and mRNA expression levels were increased. The total antioxidant (T-AOC) and activities of antioxidant enzymes including copper zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glutathione-s-transferase (GST) were decreased, and the glutathione (GSH) contents as well were decreased in the kidney. Concurrently, the renal CuZn-SOD, Mn-SOD, CAT, GSH-Px, GST, and GR mRNA expression levels were decreased. The above-mentioned results showed that dietary NiCl2 in excess of 300 mg/kg caused renal oxidative damage by reducing mRNA expression levels and activities of antioxidant enzymes, and then enhancing free radicals generation, lipid peroxidation, and DNA oxidation.

  3. Radiation damage in rat kidney microvasculature.

    PubMed

    Nelson, A C; Shah-Yukich, A; Babayan, R

    1984-01-01

    Scanning electron microscopy (SEM) combined with a specialized polymer injection casting technique permits the analysis of radiation induced damage in rat kidney glomeruli. A lead shielding device is constructed to enable the irradiation of the living rat left kidney, while the remainder of the animal is shielded from the dose, the right kidney serves as a control. The source of radiation is 137Cs which produces 0.66 MeV gamma-rays to achieve a kidney dose of 100 rad and 5000 rad in these experiments. Radiation damage to kidney glomeruli is assessed at intervals of 0, 1, 3 and 7 days post-irradiation at the two dose levels. It is found that radiation damage to kidney glomeruli is expressed morphologically at 7 days post-irradiation at the 100 rad dose level, while glomerular damage is apparent as early as 3 days post-irradiation at the 5000 rad dose level. Moreover, by 7 days post-irradiation with a 5000 rad dose, the kidney glomerulus thoroughly degenerates to a leaky fused mass of vessels. From a morphological viewpoint, kidney glomeruli are significantly more sensitive to radiation than surrounding vasculature. The methods developed here for assessment of radiation damage are highly repeatable and could serve as a standard technique in radiobiology.

  4. The kidney and hypertension: causes and treatment.

    PubMed

    Sica, Domenic A

    2008-07-01

    Chronic kidney disease is both a cause and a consequence of hypertension. Extracellular volume expansion is an important, if not the most important, contributing factor to hypertension seen in chronic kidney disease. Beyond volume expansion, chronic kidney disease-related hypertension is without truly defining characteristics. Consequently, the sequencing of antihypertensive medications for the patient with chronic kidney disease and hypertension becomes arbitrary. Prescription practice in such patients should be mindful of the need for multiple drug classes with at least one of them being a diuretic. Blood pressure goals in the patient with chronic kidney disease and hypertension are set at lower levels than those for patients with essential hypertension alone. It remains to be determined to what level blood pressure should be lowered in the patient with chronic kidney disease, however.

  5. Biomarkers in chronic kidney disease, from kidney function to kidney damage

    PubMed Central

    Lopez-Giacoman, Salvador; Madero, Magdalena

    2015-01-01

    Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m2. Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD. PMID:25664247

  6. Thrombophilia and Damage of Kidney During Pregnancy

    PubMed Central

    Giovanni, Larciprete; Maria, Liumbruno Giancarlo; Mauro, Rongioletti; Carlotta, Montagnoli; Federica, Rossi; Fabrizio, Papa; Sheba, Jarvis; Giuseppe, Di Pierro; Alessandro, Bompiani; Elio, Cirese; Herbert, Valensise

    2011-01-01

    Objectives It’s known that heritable thrombophilias are a risk factor for the development of obstetrics complications associated to inadequate uterine-placental circulation, as pre-eclampsia/eclampsia, HELLP syndrome, placental abruption and intrauterine growth restriction (IUGR), however it was never investigated the role that they could have in the renal failure associated to such conditions. The purpose of this study is to evaluate if thrombophilia itself that predispose to a possible renal damage or if its occurrence determines a more severe involvement of the kidneys in the course of these obstetric pathologies. Methods In the study were enrolled 301 pregnant women, who carried a thrombophilic state, 125 of whom (B group) has had an obstetric complication. In all the women the renal function was assessed taking into consideration proteinuria, creatininaemia and hypalbuminaemia. Results Of the three parameters which have been considered as evidence of a severe renal involvement the hypalbuminaemia appears statistically significant compared to the controls. Even creatinaemia is significantly increased in pregnant women with an Anthithrombin deficiency, and increased levels are detected in women with Factor V Leiden. Conclusions In obstetric complications associated to thrombophilic state could be a more severe involvement of the kidney. PMID:22905298

  7. Marathon Running May Cause Short-Term Kidney Injury

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164324.html Marathon Running May Cause Short-Term Kidney Injury But ... of endurance are also tough on the kidneys. "Marathon runners demonstrate transient or reverse short-term kidney ...

  8. Increased kidney metabolism as a pathway to kidney tissue hypoxia and damage: effects of triiodothyronine and dinitrophenol in normoglycemic rats.

    PubMed

    Friederich-Persson, Malou; Persson, Patrik; Fasching, Angelica; Hansell, Peter; Nordquist, Lina; Palm, Fredrik

    2013-01-01

    Intrarenal tissue hypoxia is an acknowledged common pathway to end-stage renal disease in clinically common conditions associated with development of chronic kidney disease, such as diabetes and hypertension. In diabetic kidneys, increased oxygen metabolism mediated by mitochondrial uncoupling results in decreased kidney oxygen tension (PO2) and contributes to the development of diabetic nephropathy. The present study investigated whether increased intrarenal oxygen metabolism per se can cause intrarenal tissue hypoxia and kidney damage, independently of confounding factors such as hyperglycemia and oxidative stress. Male Sprague-Dawley rats were untreated or treated with either triiodothyronine (T3, 10 g/kg bw/day, subcutaneously for 10 days) or the mitochondria uncoupler dinitrophenol (DNP, 30 mg/kg bw/day, oral gavage for 14 days), after which in vivo kidney function was evaluated in terms of glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Transonic, PAH clearance), cortical PO2 (Clark-type electrodes), kidney oxygen consumption (QO2), and proteinuria. Administration of both T3 and DNP increased kidney QO2 and decreased PO2 which resulted in proteinuria. However, GFR and RBF were unaltered by either treatment. The present study demonstrates that increased kidney metabolism per se can cause intrarenal tissue hypoxia which results in proteinuria. Increased kidney QO2 and concomitantly reduced PO2 may therefore be a mechanism for the development of chronic kidney disease and progression to end-stage renal disease.

  9. Smoking in Pregnancy Tied to Kidney Damage in Kids

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_162696.html Smoking in Pregnancy Tied to Kidney Damage in Kids ... and about 17 percent of those women continued smoking while pregnant, the study authors said. Children of ...

  10. Damage Caused by the Rogue Trustee

    ERIC Educational Resources Information Center

    O'Banion, Terry

    2009-01-01

    Fifty-nine community college presidents and chancellors in 16 states report on the damage caused by rogue trustees. While the damage to presidents, other trustees, and faculty and staff is alarming, the damage these trustees cause the college suggests that the rogue trustee may be the single most destructive force ever to plague an educational…

  11. Past Kidney Damage Linked to Pregnancy Problems

    MedlinePlus

    ... to Pregnancy Problems The high blood pressure condition preeclampsia is 6 times more common, study finds To ... had much higher rates of a condition called preeclampsia that causes high blood pressure and other problems ...

  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. 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.

  14. Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury

    PubMed Central

    Maejima, Ikuko; Takahashi, Atsushi; Omori, Hiroko; Kimura, Tomonori; Takabatake, Yoshitsugu; Saitoh, Tatsuya; Yamamoto, Akitsugu; Hamasaki, Maho; Noda, Takeshi; Isaka, Yoshitaka; Yoshimori, Tamotsu

    2013-01-01

    Diverse causes, including pathogenic invasion or the uptake of mineral crystals such as silica and monosodium urate (MSU), threaten cells with lysosomal rupture, which can lead to oxidative stress, inflammation, and apoptosis or necrosis. Here, we demonstrate that lysosomes are selectively sequestered by autophagy, when damaged by MSU, silica, or the lysosomotropic reagent L-Leucyl-L-leucine methyl ester (LLOMe). Autophagic machinery is recruited only on damaged lysosomes, which are then engulfed by autophagosomes. In an autophagy-dependent manner, low pH and degradation capacity of damaged lysosomes are recovered. Under conditions of lysosomal damage, loss of autophagy causes inhibition of lysosomal biogenesis in vitro and deterioration of acute kidney injury in vivo. Thus, we propose that sequestration of damaged lysosomes by autophagy is indispensable for cellular and tissue homeostasis. PMID:23921551

  15. A model for damage of microheterogeneous kidney stones

    NASA Astrophysics Data System (ADS)

    Szeri, Andrew J.; Zohdi, Tarek I.; Blake, John R.

    2005-04-01

    In this paper, a theoretical framework is developed for the mechanics of kidney stones with an isotropic, random microstructure-such as those comprised of cystine or struvite. The approach is based on a micromechanical description of kidney stones comprised of crystals in a binding matrix. Stress concentration functions are developed to determine load sharing of the particle phase and the binding matrix phase. As an illustration of the theory, the fatigue of kidney stones subject to shock wave lithotripsy is considered. Stress concentration functions are used to construct fatigue life estimates for each phase, as a function of the volume fraction and of the mechanical properties of the constituents, as well as the loading from SWL. The failure of the binding matrix is determined explicitly in a model for the accumulation of distributed damage. Also considered is the amount of material damaged in a representative non-spherical collapse of a cavitation bubble near the stone surface. The theory can be used to assess the importance of microscale heterogeneity on the comminution of renal calculi and to estimate the number of cycles to failure in terms of measurable material properties.

  16. 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 ...

  17. Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

    PubMed Central

    Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C.; Khadayate, Sanjay; Mas, Valeria R.; Nitsch, Dorothea D.; Wang, Zhen; Norman, Jill T.; Wilcox, Christopher S.; Wheeler, David C.; Leiper, James

    2015-01-01

    Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. PMID:25855779

  18. Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom

    PubMed Central

    Okamoto, Cinthya Kimori; van den Berg, Carmen W.; Masashi, Mizuno; Gonçalves-de-Andrade, Rute M.; Tambourgi, Denise V.

    2017-01-01

    Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D) is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP). Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism. PMID:28257106

  19. Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom.

    PubMed

    Okamoto, Cinthya Kimori; van den Berg, Carmen W; Masashi, Mizuno; Gonçalves-de-Andrade, Rute M; Tambourgi, Denise V

    2017-03-02

    Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D) is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP). Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism.

  20. Indoxyl sulphate and kidney disease: Causes, consequences and interventions.

    PubMed

    Ellis, Robert J; Small, David M; Vesey, David A; Johnson, David W; Francis, Ross; Vitetta, Luis; Gobe, Glenda C; Morais, Christudas

    2016-03-01

    In the last decade, chronic kidney disease (CKD), defined as reduced renal function (glomerular filtration rate (GFR) < 60 mL/min per 1.73 m(2) ) and/or evidence of kidney damage (typically manifested as albuminuria) for at least 3 months, has become one of the fastest-growing public health concerns worldwide. CKD is characterized by reduced clearance and increased serum accumulation of metabolic waste products (uremic retention solutes). At least 152 uremic retention solutes have been reported. This review focuses on indoxyl sulphate (IS), a protein-bound, tryptophan-derived metabolite that is generated by intestinal micro-organisms (microbiota). Animal studies have demonstrated an association between IS accumulation and increased fibrosis, and oxidative stress. This has been mirrored by in vitro studies, many of which report cytotoxic effects in kidney proximal tubular cells following IS exposure. Clinical studies have associated IS accumulation with deleterious effects, such as kidney functional decline and adverse cardiovascular events, although causality has not been conclusively established. The aims of this review are to: (i) establish factors associated with increased serum accumulation of IS; (ii) report effects of IS accumulation in clinical studies; (iii) critique the reported effects of IS in the kidney, when administered both in vivo and in vitro; and (iv) summarize both established and hypothetical therapeutic options for reducing serum IS or antagonizing its reported downstream effects in the kidney.

  1. 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.

  2. Textile damage caused by vapour cloud explosions.

    PubMed

    Was-Gubala, J; Krauss, W

    2004-01-01

    The aim of the project was to investigate the damage to garments caused by particular vapour cloud explosions. The authors would like to be able to provide investigators with specific information on how to link clothes to a specific type of crime: a particular case study was the inspiration for the examinations. Experiments were carried out in the fire reconstruction chamber of the laboratory using a selection of 26 clothes and 15 household garments differing in colour, fibre composition and textile construction.

  3. DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers

    PubMed Central

    Schupp, Nicole; Stopper, Helga; Heidland, August

    2016-01-01

    Patients with chronic kidney disease (CKD) exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients' burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis-block micronucleus assay, the comet assay, and the quantification of 8-oxo-7,8-dihydro-2′-deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker's potential to predict clinical outcomes. PMID:27313827

  4. PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

    EPA Science Inventory

    Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin.

    Arsenic causes cancer in human skin, urinary bladder, lung, liver and kidney and is a significant world-wide public health problem. Although the metabolism of inorganic arsenic is ...

  5. Acute kidney injury caused by zonisamide-induced hypersensitivity syndrome.

    PubMed

    Fujita, Yoshiro; Hasegawa, Midori; Nabeshima, Kuihiro; Tomita, Makoto; Murakami, Kazutaka; Nakai, Shigeru; Yamakita, Takashi; Matsunaga, Kayoko

    2010-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction affecting multiple organs caused by drug treatment. The current report describes a man who was prescribed zonisamide for epilepsy and subsequently developed widespread skin rash, acute kidney injury, high-grade fever, eosinophilia, liver dysfunction, lymphadenopathy and an increase in antihuman herpesvirus-6 immunoglobulin G titer. Hypersensitivity to zonisamide was confirmed by the skin patch test. Based on these findings, the patient was diagnosed with DRESS/DIHS caused by zonisamide. This is the first report of acute kidney injury due to zonisamide-induced DRESS/DIHS.

  6. Oral nanoparticulate curcumin combating arsenic-induced oxidative damage in kidney and brain of rats.

    PubMed

    Sankar, Palanisamy; Telang, Avinash Gopal; Kalaivanan, Ramya; Karunakaran, Vijayakaran; Suresh, Subramaniyam; Kesavan, Manickam

    2016-03-01

    Arsenic exposure through drinking water causes oxidative stress and tissue damage in the kidney and brain. Curcumin (CUR) is a good antioxidant with limited clinical application because of its hydrophobic nature and limited bioavailability, which can be overcome by the encapsulation of CUR with nanoparticles (NPs). The present study investigates the therapeutic efficacy of free CUR and NP-encapsulated CUR (CUR-NP) against sodium arsenite-induced renal and neuronal oxidative damage in rat. The CUR-NP prepared by emulsion technique and particle size ranged between 120 and 140 nm, with the mean particle size being 130.8 nm. Rats were divided into five groups (groups 1-5) with six animals in each group. Group 1 served as control. Group 2 rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5 were treated with arsenic as in Group 2; however, these animals were also administered with empty NPs, CUR (100 mg/kg body weight), and CUR-NP (100 mg/kg), respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic exposure significantly increased serum urea nitrogen and creatinine levels. Arsenic increased lipid peroxidation (LPO), reduced glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were depleted significantly in both kidney and brain. Treatment with free CUR and CUR-NP decreased the LPO and increased the enzymatic and nonenzymatic antioxidant system in kidney and brain. Histopathological examination showed that kidney and brain injury mediated by arsenic was ameliorated by treatment. However, the amelioration percentage indicates that CUR-NP had marked therapeutic effect on arsenic-induced oxidative damage in kidney and brain tissues.

  7. Functional and morphologic damage in the neonatally irradiated canine kidney

    SciTech Connect

    Peneyra, R.S.; Jaenke, R.S.

    1985-11-01

    Perinatal irradiation of the developing kidney results in progressive glomerulosclerosis (PGS) and renal failure. This syndrome may result from direct radiation damage to mature deep cortical nephrons and/or nephron functional adaptations resulting from outer cortical nephron ablation. Beagle dogs received single, whole-body exposures (330 R) to /sup 60/Co gamma radiation at 4 days of age (IR4) to study the combined effects of direct radiation damage and nephron loss, or at 30 days of age (IR30) to study the effects of renal irradiation alone. To study the effects of nephron loss alone, dogs underwent unilateral nephrectomy (UN4) or superficial hyperthermic renal ablation (HY4) at 4 days of age. Nephron loss due to irradiation (IR4) and partial renal ablation (UN4 and HY4) was associated with compensatory nephron hypertrophy and increased single nephron glomerular filtration rate (SNGFR), while irradiation at 30 days resulted in transitory decreased SNGFR. Similar degrees of PGS occurred in IR4 dogs which experienced both irradiation and loss of nephrons and UN4 and HY4 dogs which experienced only loss of nephrons. PGS of lesser severity also occurred in IR30 dogs. These findings indicate that PGS associated with perinatal renal irradiation results from direct radiation damage to deep cortical nephrons and compensatory functional changes occurring in response to loss of renal mass.

  8. Oxidative DNA Damage in Kidneys and Heart of Hypertensive Mice Is Prevented by Blocking Angiotensin II and Aldosterone Receptors

    PubMed Central

    Brand, Susanne; Amann, Kerstin; Mandel, Philipp; Zimnol, Anna; Schupp, Nicole

    2014-01-01

    Introduction Recently, we could show that angiotensin II, the reactive peptide of the blood pressure-regulating renin-angiotensin-aldosterone-system, causes the formation of reactive oxygen species and DNA damage in kidneys and hearts of hypertensive mice. To further investigate on the one hand the mechanism of DNA damage caused by angiotensin II, and on the other hand possible intervention strategies against end-organ damage, the effects of substances interfering with the renin-angiotensin-aldosterone-system on angiotensin II-induced genomic damage were studied. Methods In C57BL/6-mice, hypertension was induced by infusion of 600 ng/kg • min angiotensin II. The animals were additionally treated with the angiotensin II type 1 receptor blocker candesartan, the mineralocorticoid receptor blocker eplerenone and the antioxidant tempol. DNA damage and the activation of transcription factors were studied by immunohistochemistry and protein expression analysis. Results Administration of angiotensin II led to a significant increase of blood pressure, decreased only by candesartan. In kidneys and hearts of angiotensin II-treated animals, significant oxidative stress could be detected (1.5-fold over control). The redox-sensitive transcription factors Nrf2 and NF-κB were activated in the kidney by angiotensin II-treatment (4- and 3-fold over control, respectively) and reduced by all interventions. In kidneys and hearts an increase of DNA damage (3- and 2-fold over control, respectively) and of DNA repair (3-fold over control) was found. These effects were ameliorated by all interventions in both organs. Consistently, candesartan and tempol were more effective than eplerenone. Conclusion Angiotensin II-induced DNA damage is caused by angiotensin II type 1 receptor-mediated formation of oxidative stress in vivo. The angiotensin II-mediated physiological increase of aldosterone adds to the DNA-damaging effects. Blocking angiotensin II and mineralocorticoid receptors therefore

  9. Coccidian Infection Causes Oxidative Damage in Greenfinches

    PubMed Central

    Sepp, Tuul; Karu, Ulvi; Blount, Jonathan D.; Sild, Elin; Männiste, Marju; Hõrak, Peeter

    2012-01-01

    The main tenet of immunoecology is that individual variation in immune responsiveness is caused by the costs of immune responses to the hosts. Oxidative damage resulting from the excessive production of reactive oxygen species during immune response is hypothesized to form one of such costs. We tested this hypothesis in experimental coccidian infection model in greenfinches Carduelis chloris. Administration of isosporan coccidians to experimental birds did not affect indices of antioxidant protection (TAC and OXY), plasma triglyceride and carotenoid levels or body mass, indicating that pathological consequences of infection were generally mild. Infected birds had on average 8% higher levels of plasma malondialdehyde (MDA, a toxic end-product of lipid peroxidation) than un-infected birds. The birds that had highest MDA levels subsequent to experimental infection experienced the highest decrease in infection intensity. This observation is consistent with the idea that oxidative stress is a causative agent in the control of coccidiosis and supports the concept of oxidative costs of immune responses and parasite resistance. The finding that oxidative damage accompanies even the mild infection with a common parasite highlights the relevance of oxidative stress biology for the immunoecological research. PMID:22615772

  10. Kidney allograft pyelonephritis caused by Salmonella enterica serovar Schwarzengrund.

    PubMed

    Ito, Kenta; Nishio, Haruomi; Iwatani, Yuji; Yamada, Ryo; Okawa, Takao; Yamamoto, Takumi; Murakami, Masaaki; Matsuo, Yoko; Matsuo, Ken; Tanaka, Satoshi; Mori, Kiyoshi; Mori, Noriko

    2017-03-13

    Kidney transplant recipients (KTRs) taking immunosuppressive drugs have a 20-fold greater risk of nontyphoidal Salmonella (NTS) infection than the healthy adult population. Among KTRs, the urinary tract is the most common site of infection. However, few cases of urinary tract infection caused by NTS have been documented in KTRs, and only one in Japan. Furthermore, it frequently induces acute allograft rejection with high mortality. Salmonella enterica subsp. enterica serovar Schwarzengrund (S. Schwarzengrund) is now among the more common Salmonella serovars isolated in Japan and is likely to be invasive. We present a case of a 45-year old female with vesicoureteral reflux to her transplanted kidney who developed kidney allograft pyelonephritis caused by S. Schwarzengrund. She was admitted to our hospital with fever, urodynia, lower abdominal pain, gross hematuria, and cloudy urine. Urine cultures were positive for S. Schwarzengrund. Exposure to cats, especially stray cats, were identified as the most likely source. We administered antibiotics for 4 weeks (ceftriaxone then amoxicillin, each for 2 weeks) and educated her about pet safety. She experienced no recurrence of infection or clinical kidney allograft rejection for 3 months post-treatment. NTS should be considered as a possible pathogen of urinary tract infection among KTRs, especially in cases with animal exposure or structural urologic abnormalities. When the pathogen is NTS, appropriate antibiotics and treatment periods are essential for preventing recurrence and allograft rejection after the completion of treatment.

  11. Insulin-mediated oxidative stress and DNA damage in LLC-PK1 pig kidney cell line, female rat primary kidney cells, and male ZDF rat kidneys in vivo.

    PubMed

    Othman, Eman Maher; Kreissl, Michael C; Kaiser, Franz R; Arias-Loza, Paula-Anahi; Stopper, Helga

    2013-04-01

    Hyperinsulinemia, a condition with excessively high insulin blood levels, is related to an increased cancer incidence. Diabetes mellitus is the most common of several diseases accompanied by hyperinsulinemia. Because an elevated kidney cancer risk was reported for diabetic patients, we investigated the induction of genomic damage by insulin in LLC-PK1 pig kidney cells, rat primary kidney cells, and ZDF rat kidneys. Insulin at a concentration of 5nM caused a significant increase in DNA damage in vitro. This was associated with the formation of reactive oxygen species (ROS). In the presence of antioxidants, blockers of the insulin, and IGF-I receptors, and a phosphatidylinositol 3-kinase inhibitor, the insulin-mediated DNA damage was reduced. Phosphorylation of protein kinase B (PKB or AKT) was increased and p53 accumulated. Inhibition of the mitochondrial and nicotinamide adenine dinucleotide phosphatase oxidase-related ROS production reduced the insulin-mediated damage. In primary rat cells, insulin also induced genomic damage. In kidneys from healthy, lean ZDF rats, which were infused with insulin to yield normal or high blood insulin levels, while keeping blood glucose levels constant, the amounts of ROS and the tumor protein (p53) were elevated in the high-insulin group compared with the control level group. ROS and p53 were also elevated in diabetic obese ZDF rats. Overall, insulin-induced oxidative stress resulted in genomic damage. If the same mechanisms are active in patients, hyperinsulinemia might cause genomic damage through the induction of ROS contributing to the increased cancer risk, against which the use of antioxidants and/or ROS production inhibitors might exert protective effects.

  12. Ammonium dichromate poisoning: A rare cause of acute kidney injury.

    PubMed

    Radhakrishnan, H; Gopi, M; Arumugam, A

    2014-11-01

    Ammonium dichromate is an inorganic compound frequently used in screen and color printing. Being a strong oxidizing agent, it causes oxygen free radical injury resulting in organ failure. We report a 25-year-old female who presented with acute kidney injury after consumption of ammonium dichromate. She was managed successfully with hemodialysis and supportive measures. This case is reported to highlight the toxicity of ammonium dichromate.

  13. Mutations in mitochondrial DNA causing tubulointerstitial kidney disease

    PubMed Central

    Mallett, Andrew; Posse, Viktor; Moreno, Pablo; Sciacovelli, Marco; Duff, Jennifer; Wiesener, Michael S.; Hudson, Gavin; Gustafsson, Claes M.; Chinnery, Patrick F.; Maxwell, Patrick H.

    2017-01-01

    Tubulointerstitial kidney disease is an important cause of progressive renal failure whose aetiology is incompletely understood. We analysed a large pedigree with maternally inherited tubulointerstitial kidney disease and identified a homoplasmic substitution in the control region of the mitochondrial genome (m.547A>T). While mutations in mtDNA coding sequence are a well recognised cause of disease affecting multiple organs, mutations in the control region have never been shown to cause disease. Strikingly, our patients did not have classical features of mitochondrial disease. Patient fibroblasts showed reduced levels of mitochondrial tRNAPhe, tRNALeu1 and reduced mitochondrial protein translation and respiration. Mitochondrial transfer demonstrated mitochondrial transmission of the defect and in vitro assays showed reduced activity of the heavy strand promoter. We also identified further kindreds with the same phenotype carrying a homoplasmic mutation in mitochondrial tRNAPhe (m.616T>C). Thus mutations in mitochondrial DNA can cause maternally inherited renal disease, likely mediated through reduced function of mitochondrial tRNAPhe. PMID:28267784

  14. Careful: Acetaminophen in Pain Relief Medicines Can Cause Liver Damage

    MedlinePlus

    ... Careful: Acetaminophen in pain relief medicines can cause liver damage Share Tweet Linkedin Pin it More sharing ... word or may have the abbreviation "APAP." Severe liver damage may occur and may lead to death ...

  15. Parents: Acetaminophen in Pain Relief Medicines Can Cause Liver Damage

    MedlinePlus

    ... Parents: Acetaminophen in pain relief medicines can cause liver damage Share Tweet Linkedin Pin it More sharing ... whole word or may have the abbreviation "APAP." Liver damage: Giving your child more acetaminophen than directed ...

  16. Landslide Caused Damages in a Gallery

    NASA Astrophysics Data System (ADS)

    Poisel, R.; Mair am Tinkhof, K.; Preh, A.

    2016-06-01

    On October 5th, 2010, cracks were found in a gallery 1.8 m high and 1.4 m wide. The gallery is 100 years old, runs parallel to a valley flank and was excavated in a tectonically strongly stressed, weathered and slightly dipping sandwich of clayey shales, sandstones and marls. The cracks in the roof as well as in the invert ran parallel to the axis of the gallery. Monitoring showed that crack widths were increasing 1.5 mm per year, sidewall distances were increasing 3.5 mm per year, whereas the height of the gallery was decreasing 2.5 mm per year. After eliminating several possible causes of cracking, a landslide producing the damages had to be taken into consideration. Monitoring of the valley flank surface as well as inclinometer readings revealed that a landslide was occurring, loading the gallery lining. Most probably the landslide had been reactivated by excessive rainfall in 2009 as well as by works for the renewal of a weir in the valley bottom. As stabilization of the slope was not an option for several reasons, it was decided to replace the gallery by a new one deeper inside the slope, which will be ready for operation in 2017. Thus the old gallery has to be kept in operation till then and it was decided to reinforce the old gallery by a heavily reinforced shotcrete lining 10 cm thick. As slope displacements went on, cracks in the shotcrete lining developed with a completely different pattern: in the section where the gallery lies completely in the landslide shear zone no cracks formed until now due to heavy reinforcement, whereas in the transition sections stable ground-landslide and landslide-stable ground diagonal tension cracks in the roof due to shear by the landslide developed. Numerical models showed that cracking and spalling of the shotcrete lining would occur only after some centimetres of additional displacements of the slope, which hopefully will not occur before 2017.

  17. Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats.

    PubMed

    Awodele, Olufunsho; Adeneye, Adejuwon Adewale; Aiyeola, Sheriff Aboyade; Benebo, Adokiye Senibo

    2015-12-01

    There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl(-), HCO3(-)), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (p<0.05) increases in serum Na+, K+, Cl(-), urea and creatinine. CCl4 also caused significant (p<0.05) decreases in renal tissue SOD, CAT and GSH and significant (p<0.05) increases in MDA. The oral MIASE treatment (125-500 mg/kg) was found to significantly (p<0.05) attenuate the increase in serum electrolytes, urea and creatinine. Similarly, MIASE significantly (p<0.05) attenuated the decrease in SOD, CAT and GSH levels and correspondingly attenuated increases in MDA. Mangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology.

  18. Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats

    PubMed Central

    Adeneye, Adejuwon Adewale; Aiyeola, Sheriff Aboyade; Benebo, Adokiye Senibo

    2015-01-01

    There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl−, HCO3−), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (p<0.05) increases in serum Na+, K+, Cl−, urea and creatinine. CCl4 also caused significant (p<0.05) decreases in renal tissue SOD, CAT and GSH and significant (p<0.05) increases in MDA. The oral MIASE treatment (125-500 mg/kg) was found to significantly (p<0.05) attenuate the increase in serum electrolytes, urea and creatinine. Similarly, MIASE significantly (p<0.05) attenuated the decrease in SOD, CAT and GSH levels and correspondingly attenuated increases in MDA. Mangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology. PMID:27486379

  19. Impact of antihypertensive therapy on progressive kidney damage.

    PubMed

    Dworkin, L D; Benstein, J A

    1989-06-01

    Our ability to measure precisely the pressures and flows within the glomerular microcirculation has enabled us to begin to unravel the complex relationship between systemic hypertension and kidney disease. Although a number of factors have been implicated in the development of glomerular sclerosis, one consistent finding has been that glomerular injury occurs when elevated pressures are transmitted to the glomerular capillaries. Intrarenal hypertension, in conjunction with renal hypertrophy, and, possibly, disturbances in lipid metabolism and blood coagulation constitute secondary processes through which those nephrons not severely injured by the primary renal disease are eventually destroyed. Ultimately, all renal function is lost. Clinically, increased glomerular pressure is likely to contribute to glomerular injury in those patients in whom hypertension and renal insufficiency coexist. In patients with diabetes, as yet unidentified factors cause preglomerular resistance to fall so that glomerular hypertension develops even in the absence of elevation in systemic blood pressure. Although no therapy has been proven to slow the rate of progression to end stage renal failure in humans, a number of promising interventions have been identified. These include dietary protein or salt restriction, and medication, with either converting enzyme inhibitors or calcium channel blockers.

  20. Ultrastructural pathological changes in mice kidney caused by Plasmodium berghei infection.

    PubMed

    Pulido-Méndez, M; Finol, H J; Girón, M E; Aguilar, I

    2006-01-01

    Malaria, a common health problem in certain parts of the world, has a considerable morbidity and mortality. This work reports under electron microscopy studies serious ultrastructural kidney damage such as extensive cytoplasmic vacuolation, vesiculation and autophagic vacuoles in proximal tubular cells. A thickened endothelial wall on peritubular capillary, interdigitation disorganization and significant decrease of their number in some areas were detected. Swollen rough endoplasmic reticulum, swollen mitochondria, and parasitized erythrocytes were observed. Many epithelial cells exhibited cytoplasmic areas of autophagia and a myelin-like form. A tubular cell presented severe cytoarchitecture alterations. Abundant lipid droplets were noticed. Almost total loss of interdigitations, rough endoplasmic reticulum vesiculation, peritubular capillaries with endothelial cells thickened cytoplasm, papillary processes projected to the lumen, and an inflammatory infiltrate of macrophages were also observed. These ultrastructural kidney changes could cause, on the basis of their clinical and pathologic expressions, a fat accumulation, an acute temporary reversible glomerulonephritis, a chronic progressive irreversible glomerulonephritis, and an acute renal failure (ARF).

  1. Zinc prevention of electromagnetically induced damage to rat testicle and kidney tissues.

    PubMed

    Ozturk, Ahmet; Baltaci, Abdülkerim Kasim; Mogulkoc, Rasim; Oztekin, Esma

    2003-01-01

    The aim of this study was to investigate the extent of lipid peroxidation when zinc is administered to rats periodically exposed to a 50-Hz electromagnetic field for 5 min at a time over a period of 6 mo. Twenty-four Sprague-Dawley adult male rats were subdivided in groups of eight animals each. Group 1 served as untreated controls, group 2 was exposed to an electromagnetic field but received no additional treatment, and group 3 was exposed to electromagnetic radiation and treated with 3-mg/kg daily intraperitoneal injections of zinc sulfate. The erythrocyte glutathione activity (GSH) and the plasma, testicle, and kidney tissue levels of zinc (Zn) and of malondialdehyde (MDA) were measured in all of the animals. The plasma and testicle MDA levels in group 2 were higher than those in groups 1 and 3, with group 3 values significantly higher than those in group 1 (p<0.001). The kidney MDA levels in group 2 were higher than in groups 1 and 3 (p<0.001). The erythrocyte GSH level was lower in group 2 than in groups 1 and 3, with group 1 significantly lower than group 3 (p<0.001). In testicle and kidney tissues, the GSH levels in group 1 were lower than for groups 2 and 3, with group 2 significantly lower than group 3 (p<0.001) The plasma zinc levels were highest in group 3, followed by group 1 and group 2, which showed the lowest value (p<0.001). These results indicate that testicle and kidney tissue damage caused by periodic exposure to an electromagnetic field are ameliorated or prevented by zinc supplementation.

  2. 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

  3. Mitochondrial NADP(+)-Dependent Isocitrate Dehydrogenase Deficiency Exacerbates Mitochondrial and Cell Damage after Kidney Ischemia-Reperfusion Injury.

    PubMed

    Han, Sang Jun; Jang, Hee-Seong; Noh, Mi Ra; Kim, Jinu; Kong, Min Jung; Kim, Jee In; Park, Jeen-Woo; Park, Kwon Moo

    2017-04-01

    Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance. Ischemia-reperfusion (I/R) is one of most common causes of AKI. I/R disrupts the mitochondrial redox balance, resulting in oxidative damage to mitochondria and cells. Here, we investigated the role of IDH2 in I/R-induced AKI. I/R injury in mice led to the inactivation of IDH2 in kidney tubule cells. Idh2 gene deletion exacerbated the I/R-induced increase in plasma creatinine and BUN levels and the histologic evidence of tubule injury, and augmented the reduction of NADPH levels and the increase in oxidative stress observed in the kidney after I/R. Furthermore, Idh2 gene deletion exacerbated I/R-induced mitochondrial dysfunction and morphologic fragmentation, resulting in severe apoptosis in kidney tubule cells. In cultured mouse kidney proximal tubule cells, Idh2 gene downregulation enhanced the mitochondrial damage and apoptosis induced by treatment with hydrogen peroxide. This study demonstrates that Idh2 gene deletion exacerbates mitochondrial damage and tubular cell death via increased oxidative stress, suggesting that IDH2 is an important mitochondrial antioxidant enzyme that protects cells from I/R insult.

  4. Multiple organ damage caused by tumor necrosis factor and prevented by prior neutrophil depletion.

    PubMed

    Mallick, A A; Ishizaka, A; Stephens, K E; Hatherill, J R; Tazelaar, H D; Raffin, T A

    1989-05-01

    The effect of TNF on nonpulmonary multiple organ damage (MOD) was studied. Since polymorphonuclear leukocytes (PMN) are thought to play an important role in septic or TNF-induced MOD, we investigated both neutrophil sufficient (PMN+) and neutropenic (PMN-) guinea pigs. Sepsis was induced by Escherichia coli administration (2 x 10(9)/kg) or recombinant human TNF (1.4 x 10(6) U/kg) was infused into PMN+ and PMN- guinea pigs. During necropsy, the PMN+/TNF and PMN+/E coli animals exhibited marked damage in the adrenal glands, kidneys and liver as evidenced by hemorrhage, congestion, and PMN sequestration on histopathologic examination. There was also increased tissue albumin accumulation in the adrenal glands, kidneys, spleen, heart, and liver as demonstrated by 125I-labeled albumin determinations. In contrast, the PMN-/TNF group did not reveal histopathologic damage in any organ system and there was no abnormal organ accumulation of 125I-albumin. However, in PMN-/E coli animals, marked histopathologic damage in the adrenal glands and liver was evident. Furthermore, there were marked accumulations of 125I-albumin in the adrenals, heart, kidneys, liver, and spleen. Moreover, the PMN-/E coli guinea pigs had a much greater accumulation (p less than 0.01) of 125I-albumin in the kidneys than any other group including the PMN+/E coli group. Thus, nonpulmonary MOD in guinea pigs is caused by TNF administration and can be prevented by PMN depletion. However, while E coli administration also caused marked nonpulmonary MOD in neutrophil sufficient guinea pigs, equivalent or greater damage was produced in neutropenic animals. This suggests that while TNF-induced MOD may be primarily mediated by PMN, E coli-induced MOD seems to be mediated by more than PMN.

  5. Multiple organ damage caused by tumor necrosis factor and prevented by prior neutrophil depletion

    SciTech Connect

    Mallick, A.A.; Ishizaka, A.; Stephens, K.E.; Hatherill, J.R.; Tazelaar, H.D.; Raffin, T.A. )

    1989-05-01

    The effect of TNF on nonpulmonary multiple organ damage (MOD) was studied. Since polymorphonuclear leukocytes (PMN) are thought to play an important role in septic or TNF-induced MOD, we investigated both neutrophil sufficient (PMN+) and neutropenic (PMN-) guinea pigs. Sepsis was induced by Escherichia coli administration (2 x 10(9)/kg) or recombinant human TNF (1.4 x 10(6) U/kg) was infused into PMN+ and PMN- guinea pigs. During necropsy, the PMN+/TNF and PMN+/E coli animals exhibited marked damage in the adrenal glands, kidneys and liver as evidenced by hemorrhage, congestion, and PMN sequestration on histopathologic examination. There was also increased tissue albumin accumulation in the adrenal glands, kidneys, spleen, heart, and liver as demonstrated by {sup 125}I-labeled albumin determinations. In contrast, the PMN-/TNF group did not reveal histopathologic damage in any organ system and there was no abnormal organ accumulation of {sup 125}I-albumin. However, in PMN-/E coli animals, marked histopathologic damage in the adrenal glands and liver was evident. Furthermore, there were marked accumulations of {sup 125}I-albumin in the adrenals, heart, kidneys, liver, and spleen. Moreover, the PMN-/E coli guinea pigs had a much greater accumulation (p less than 0.01) of {sup 125}I-albumin in the kidneys than any other group including the PMN+/E coli group. Thus, nonpulmonary MOD in guinea pigs is caused by TNF administration and can be prevented by PMN depletion. However, while E coli administration also caused marked nonpulmonary MOD in neutrophil sufficient guinea pigs, equivalent or greater damage was produced in neutropenic animals. This suggests that while TNF-induced MOD may be primarily mediated by PMN, E coli-induced MOD seems to be mediated by more than PMN.

  6. Gastrointestinal damage caused by swallowing multiple magnets.

    PubMed

    Liu, Shiqi; Li, Jianhui; Lv, Yi

    2012-09-01

    Swallowing multiple magnets is not uncommon worldwide and it frequently leads to serious consequences. However, most patients fail to receive timely and correct diagnosis and treatment. A literature search was performed to establish an algorithm for these accidents by the authors to identify relevant articles published from June 1987 to October 2010 in Google, Medline, ISI Web of Knowledge Ovid, CNKI, Korea Med and library document delivery, using search terms "magnet ingestion, " "fistula," and "perforation." A total of 149 patients with ingestion of magnetic foreign bodies from 20 countries and areas were identified. 22 of them were companioned with neurological and psychiatric disorders. Swallowing magnets occurred throughout childhood and adolescent, mostly ranging 2 to 4 years in age. Various gastrointestinal damages such as necrosis and intestinal perforation or fistula were encountered. Damage from swallowing multiple magnets carries a significant risk of morbidity and even mortality throughout childhood to adolescent worldwide. Older children and adults with neurological and psychiatric problems may be at high risk for such accidents. Early intervention is crucial.

  7. Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat

    PubMed Central

    Dhibi, Sabah; Mbarki, Sakhria; Elfeki, Abdelfettah; Hfaiedh, Najla

    2014-01-01

    Plants have historically been used in treating many diseases. Eucalyptus globules, a rich source of bioactive compounds, and have been shown to possess antioxidative properties. The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of Eucalyptus globulus extract upon acetaminophen-induced damages in kidney. Our study is realized in the Department of Biology, Faculty of Sciences of Sfax (Tunisia). 32 Wistar male rats; were divided into 4 batches: a control group (n=8), a group of rats treated with acetaminophen (goomg/kg) by intraperitoneal injection during 4 days (n=8), a group receiving Eucalyptus globulus extract (130 mg of dry leaves/kg/day) in drinking water during 42 days after 2 hours of acetaminophen administration (during 4 days) (n=8) and group received only Eucalyptus (n=8) during 42 days. After 6 weeks, animals from each group were rapidly sacrificed by decapitation. Blood serum was obtained by centrifugation. Under our experimental conditions, acetaminophen poisoning resulted in an oxidative stress evidenced by statistically significant losses in the activities of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in lipids peroxidation level in renal tissue of acetaminophen-treated group compared with the control group. Acetaminophen also caused kidney damage as evident by statistically significant (p<0.05) increase in levels of creatinine and urea and decreased levels of uric acid and proteins in blood. Histological analysis demonstrated alteration of proximal tubules, atrophy of the glomerule and dilatation of urinary space. Previous administration of plant extract is found to alleviate this acetaminophen-induced damage. PMID:24856382

  8. 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.

  9. Sodium fluoride induces apoptosis in the kidney of rats through caspase-mediated pathways and DNA damage.

    PubMed

    Song, Guo Hua; Gao, Ji Ping; Wang, Chun Fang; Chen, Chao Yang; Yan, Xiao Yan; Guo, Min; Wang, Yu; Huang, Fu Bing

    2014-09-01

    Long-term excessive sodium fluoride (NaF) intake can cause many bone diseases and nonskeletal fluorosis. The kidneys are the primary organs involved in the excretion and retention of NaF. The objective of the present study was to determine the effects of NaF treatment on renal cell apoptosis, DNA damage, and the protein expression levels of cytosolic cytochrome C (Cyt C) and cleaved caspases 9, 8, and 3 in vivo. Male Sprague-Dawley rats were divided randomly into four groups (control, low fluoride, medium fluoride, and high fluoride) and administered 0, 50, 100, and 200 mg/L of NaF, respectively, via drinking water for 120 days. Histopathological changes in the kidneys were visualized using hematoxylin and eosin staining. Renal cell apoptosis was examined using flow cytometry, and renal cell DNA damage was detected using the comet assay. Cytosolic Cyt C and cleaved caspases 9, 8, and 3 protein expression levels were visualized using immunohistochemistry and Western blotting. The results showed that NaF treatment increased apoptosis and DNA damage. In addition, NaF treatment increased the protein expression levels of cytosolic Cyt C and cleaved caspases 9, 8, and 3. These results indicated that NaF induces apoptosis in the kidney of rats through caspase-mediated pathway, and DNA damage may be involved in this process.

  10. Hypercalcemia as a Cause of Kidney Failure: Case Report

    PubMed Central

    Stojceva-Taneva, Olivera; Taneva, Borjanka; Selim, Gjulsen

    2016-01-01

    BACKGROUND: Hypercalcemia is a common manifestation in clinical practice and occurs as a result of primary hyperparathyroidism, malignancy, milk-alkali syndrome, hyper or hypothyroidism, sarcoidosis and other known and unknown causes. Patients with milk-alkali syndrome typically are presented with renal failure, hypercalcemia, and metabolic alkalosis caused by the ingestion of calcium and absorbable alkali. This syndrome is caused by high intake of milk and sodium bicarbonate. CASE PRESENTATION: We present a 28-year old male admitted to hospital with a one-month history of nausea, vomiting, epigastric pain, increased blood pressure and worsening of renal function with hypercalcemia. His serum PTH level was almost undetectable; he had mild alkalosis, renal failure with eGFR of 42 ml/min, anemia, hypertension and abnormal ECG with shortened QT interval and ST elevation in V1-V4. He had a positive medical history for calcium-containing antacids intake and after ruling out primary hyperparathyroidism, malignancy, multiple myelomas, sarcoidosis, and thyroid dysfunction, it seemed plausible to diagnose him as having the milk-alkali syndrome. CONCLUSION: Although milk-alkali syndrome currently may be more probably a result of calcium and vitamin D intake in postmenopausal women, or in elderly men with reduced kidney function taking calcium-containing medications, one should not exclude the possibility of its appearance in younger patients taking calcium-containing medications and consider it a serious condition taking into account its possibility of inducing renal insufficiency. PMID:27335601

  11. Mapping genetic determinants of kidney damage in rat models.

    PubMed

    Schulz, Angela; Kreutz, Reinhold

    2012-07-01

    During the last two decades, significant progress in our understanding of the development of kidney diseases has been achieved by unravelling the mechanisms underlying rare familial forms of human kidney diseases. Due to the genetic heterogeneity in human populations and the complex multifactorial pathogenesis of the disease phenotypes, the dissection of the genetic basis of common chronic kidney diseases (CKD) remains a difficult task. In this regard, several inbred rat models provide valuable complementary tools to uncover the genetic basis of complex renal disease phenotypes that are related to common forms of CKD. In this review, data obtained in nine experimental rat models, including the Buffalo (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki (GK), Lyon hypertensive (LH), Munich Wistar Frömter (MWF), Sabra hypertension-prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) inbred strains, that contributed to the genetic dissection of renal disease phenotypes are presented. In this panel of inbred strains, a large number of quantitative trait loci (QTL) linked to albuminuria/proteinuria and other functional or structural kidney abnormalities could be identified by QTL mapping analysis and follow-up studies including consomic and congenic rat lines. The comprehensive exploitation of the genotype-renal phenotype associations that are inherited in this panel of rat strains is suitable for making a significant contribution to the development of an integrated approach to the systems genetics of common CKD.

  12. The protective effect of Malva sylvestris on rat kidney damaged by vanadium

    PubMed Central

    2011-01-01

    Background The protective effect of the common mallow (Malva sylvestris) decoction on renal damages in rats induced by ammonium metavanadate poisoning was evaluated. On the one hand, vanadium toxicity is associated to the production of reactive oxygen species, causing a lipid peroxidation and an alteration in the enzymatic antioxidant defence. On the other hand, many medicinal plants are known to possess antioxidant and radical scavenging properties, thanks to the presence of flavonoids. These properties were confirmed in Malva sylvestris by two separate methods; namely, the Diphenyl-2-picrylhydrazyl assay and the Nitroblue Tetrazolium reduction assay. Results In 80 rats exposed to ammonium metavanadate (0.24 mmol/kg body weight in drinking water) for 90 days, lipid peroxidation levels and superoxide dismutase, catalase and glutathione peroxidase activities were measured in kidney. A significant increase in the formation of free radicals and antioxidant enzyme activities was noticed. In addition, a histological examination of kidney revealed a structural deterioration of the renal cortical capsules and a shrinking of the Bowman space. In animals intoxicated by metavanadate but also given a Malva sylvestris decoction (0.2 g dry mallow/kg body weight), no such pathologic features were observed: lipid peroxidation levels, antioxidant enzyme activities and histological features appeared normal as compared to control rats. Conclusion Malva sylvestris is proved to have a high antioxidative potential thanks to its richness in phenolic compounds. PMID:21513564

  13. Dietary fructose causes tubulointerstitial injury in the normal rat kidney.

    PubMed

    Nakayama, Takahiro; Kosugi, Tomoki; Gersch, Michael; Connor, Thomas; Sanchez-Lozada, Laura Gabriela; Lanaspa, Miguel A; Roncal, Carlos; Perez-Pozo, Santos E; Johnson, Richard J; Nakagawa, Takahiko

    2010-03-01

    Recent studies suggest that the metabolic syndrome is associated with renal disease. We previously reported that a high-fructose diet, but not a high-glucose diet, can induce metabolic syndrome and accelerate chronic renal disease in rats. We now examined the effects of a high-fructose diet on normal rat kidneys. Three groups of Sprague-Dawley rats were pair fed a special diet containing 60% fructose, 60% glucose, or control standard rat chow for 6 wk, and then histological studies were performed. The effect of fructose to induce cell proliferation in cultured proximal tubular cells was also performed. Fructose diet, but not glucose diet, significantly increased kidney weight by 6 wk. The primary finding was tubular hyperplasia and proliferation involving all segments of the proximal tubules while glomerular changes were not observed. This is the same site where the fructose transporters (GLUT2 and -5) as well as the key enzyme in fructose metabolism (ketohexokinase) were expressed. Consistently, fructose also induced proliferation of rat proximal tubular cells in culture. In vivo, tubular proliferation was also associated with focal tubular injury, with type III collagen deposition in the interstitium, an increase in alpha-smooth muscle actin positive myofibroblasts, and an increase in macrophage infiltration. In conclusion, a high-fructose diet induces cell proliferation and hyperplasia in proximal tubules, perhaps via a direct metabolic effect. The effect is independent of total energy intake and is associated with focal tubulointerstitial injury. These studies may provide a mechanism by which metabolic syndrome causes renal disease.

  14. 6. 'ROCKFILLED CRIB 350 FEET LONG, REPAIRING DAMAGES CAUSED BY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. 'ROCK-FILLED CRIB 350 FEET LONG, REPAIRING DAMAGES CAUSED BY FLOODS DURING SEASON OF 1927 TO THE DRY GULCH CANAL HEADING.' 1928 - Irrigation Canals in the Uinta Basin, Duchesne, Duchesne County, UT

  15. Unilateral nephrectomy 24 hours after bilateral kidney irradiation reduces damage to the function and structure of the remaining kidney

    SciTech Connect

    Liao, Z.X.; Travis, E.L.

    1994-09-01

    The effect of unilateral nephrectomy 24 h after irradiation on renal function and death with renal insufficiency as well as histopathological changes in the kidney was assessed. Single doses totaling 8-18 Gy were given bilaterally to unanesthetized female and male C3Hf/Kam mice. Renal function damage was assayed by blood urea nitrogen (BUN) and hematocrit (Hct). Histological damage was quantified by two parameters: kidney area and number of surviving tubule cells along the renal capsule. The number of glomeruli was scored as an indication of the number of nephrons. Changes in the two functional parameters did not appear sooner after irradiation in the nephrectomized mice than in the non-nephrectomized mice. Rather, less impairment of function was measured by both parameters in the nephrectomized mice but only after radiation doses greater than 12 Gy. The LD{sub 50} at 424 days after irradiation was also higher in the nephrectomized mice than in the mice receiving only irradiation, 13.98 Gy (95% confidence limits = 12.03, 15.93) and 11.71 Gy (95% confidence limits = 10.4, 13.1), respectively, in agreement with the data on function. Unilateral nephrectomy alone induced a 10% increase in size of the contralateral kidney. The dose-response curve for the kidney area from nephrectomized mice was parallel to and displaced above that for non-nephrectomized mice, indicating that the increase in renal mass occurred independent of and was not compromised by radiation. Unilateral nephrectomy alone induced no increase in the number of proximal tubules in the contralateral kidney. 30 refs., 9 figs., 1 tab.

  16. [DIABETIC NEPHROPATHY AS A CAUSE OF CHRONIC KIDNEY DISEASE].

    PubMed

    Kos, Ivan; Prkačin, Ingrid

    2014-12-01

    Diabetic nephropathy is the leading cause of end-stage chronic kidney disease in most developed countries. Hyperglycemia, hypertension and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Clinical picture includes a progressive increase in albuminuria, decline in glomerular filtration, hypertension, and a high risk of cardiovascular morbidity and mortality. Screening for albuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of adolescence or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with albuminuria should undergo evaluation regarding the presence of associated comorbidities, especially retinopathy and macrovascular disease. Achieving the best metabolic control (HbA1c < 7%), treating hypertension (target blood pressure < 140/85 mm Hg), using drugs with blockade effect on the renin-angiotensin-aldosterone system, treating dyslipidemia and anemia are effective strategies for preventing the development of albuminuria, delaying the progression to more advanced stages of nephropathy and reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.

  17. Vitamin D3 Reduces Tissue Damage and Oxidative Stress Caused by Exhaustive Exercise

    PubMed Central

    Ke, Chun-Yen; Yang, Fwu-Lin; Wu, Wen-Tien; Chung, Chen-Han; Lee, Ru-Ping; Yang, Wan-Ting; Subeq, Yi-Maun; Liao, Kuang-Wen

    2016-01-01

    Exhaustive exercise results in inflammation and oxidative stress, which can damage tissue. Previous studies have shown that vitamin D has both anti-inflammatory and antiperoxidative activity. Therefore, we aimed to test if vitamin D could reduce the damage caused by exhaustive exercise. Rats were randomized to one of four groups: control, vitamin D, exercise, and vitamin D+exercise. Exercised rats received an intravenous injection of vitamin D (1 ng/mL) or normal saline after exhaustive exercise. Blood pressure, heart rate, and blood samples were collected for biochemical testing. Histological examination and immunohistochemical (IHC) analyses were performed on lungs and kidneys after the animals were sacrificed. In comparison to the exercise group, blood markers of skeletal muscle damage, creatine kinase and lactate dehydrogenase, were significantly (P < 0.05) lower in the vitamin D+exercise group. The exercise group also had more severe tissue injury scores in the lungs (average of 2.4 ± 0.71) and kidneys (average of 3.3 ± 0.6) than the vitamin D-treated exercise group did (1.08 ± 0.57 and 1.16 ± 0.55). IHC staining showed that vitamin D reduced the oxidative product 4-Hydroxynonenal in exercised animals from 20.6% to 13.8% in the lungs and from 29.4% to 16.7% in the kidneys. In summary, postexercise intravenous injection of vitamin D can reduce the peroxidation induced by exhaustive exercise and ameliorate tissue damage, particularly in the kidneys and lungs. PMID:26941574

  18. Oxidative stress in kidney transplantation: causes, consequences, and potential treatment.

    PubMed

    Nafar, Mohsen; Sahraei, Zahra; Salamzadeh, Jamshid; Samavat, Shiva; Vaziri, Nosartolah D

    2011-11-01

    Oxidative stress is a major mediator of adverse outcomes throughout the course of transplantation. Transplanted kidneys are prone to oxidative stress-mediated injury by pre-transplant and post-transplant conditions that cause reperfusion injury or imbalance between oxidants and antioxidants. Besides adversely affecting the allograft, oxidative stress and its constant companion, inflammation, cause cardiovascular disease, cancer, metabolic syndrome, and other disorders in transplant recipients. Presence and severity of oxidative stress can be assessed by various biomarkers produced from interaction of reactive oxygen species with lipids, proteins, nucleic acids, nitric oxide, glutathione, etc. In addition, expression and activities of redox-sensitive molecules such as antioxidant enzymes can serve as biomarkers of oxidative stress. Via activation of nuclear factor kappa B, oxidative stress promotes inflammation which, in turn, amplifies oxidative stress through reactive oxygen species generation by activated immune cells. Therefore, inflammation markers are indirect indicators of oxidative stress. Many treatment options have been evaluated in studies conducted at different stages of transplantation in humans and animals. These studies have provided useful strategies for use in donors or in organ preservation solutions. However, strategies tested for use in post-transplant phase have been largely inconclusive and controversial. A number of therapeutic options have been exclusively examined in animal models and only a few have been tested in humans. Most of the clinical investigations have been of short duration and have provided no insight into their impact on the long-term survival of transplant patients. Effective treatment of oxidative stress in transplant population remains elusive and awaits future explorations.

  19. Ruptured Hemangioma of a Native Kidney: An Unusual Cause of Postoperative Hemorrhage in Kidney Transplant Recipients.

    PubMed

    Poznańska, Grażyna; Wlazlak, Michał; Hogendorf, Piotr; Szymański, Dariusz; Strzelczyk, Janusz; Durczyński, Adam

    2017-03-14

    BACKGROUND Retroperitoneal bleeding as a consequence of non-traumatic kidney or allograft rupture is well known, but there are no reports on hemorrhagia from a native kidney after allogeneic renal transplantation. Therefore, we present the first such case to be published and highlight the possibility of this complication after renal transplantation. CASE REPORT We report the case of a 28-year-old male patient who developed early post-transplant hemorrhagia from a ruptured native kidney. The patient underwent left-sided nephrectomy. Histopathological examination revealed ruptured hemangioma of the patient's native left kidney. The further postoperative period was not complicated. The patient was discharged on the 18th postoperative day, with good transplant function. CONCLUSIONS Transplantologists should be aware of the fact that in patients with uncontrolled blood pressure, native kidney hemangioma may rupture in the early post-transplant period, and it can be a life-threating and difficult to diagnose complication.

  20. Surgical ‘damage control’ treatment of a large retroperitoneal liposarcoma encasing a horseshoe kidney

    PubMed Central

    Andreoni, B; Chiappa, A; Pace, U; Bertani, E; Verweij, F; Orsi, F; Petralia, G; Tullii, M; Venturino, M; Pelosi, G

    2008-01-01

    Damage control is a surgical strategy for severely compromised trauma patients based on speed control of life-threatening injuries that aims to rapidly resuscitate patients in an intensive care unit (ICU). We report on the use of such therapeutic strategy in a patient affected by a retroperitoneal sarcoma concomitant to a horseshoe kidney, a relatively rare anatomical malformation. PMID:22275967

  1. Urinary Obstruction of Transplanted Kidney Caused by Uterine Adenomyosis and 2-Year Posthysterectomy Psoas Abscess in Conjunction with Transplanted Kidney

    PubMed Central

    Takezawa, Yuta; Nohara, Takahiro; Mizokami, Atsushi

    2016-01-01

    Urinary obstruction of the transplanted kidney caused by uterine leiomyoma is an extremely rare condition. To the best of our knowledge, there are only two reports in English literature. Psoas abscess secondary to renal graft pyelonephritis is also uncommon. We present this unusual case and its treatment course. A 43-year-old female presented with renal dysfunction. She was started on peritoneal dialysis from the age of 26 years and received kidney transplantation from her mother (living donor) at the age of 27 years. Computed tomography (CT) revealed right hydronephrosis and a large uterine mass compressing the distal ureter of the transplanted kidney. After a simple total hysterectomy, her renal function improved. Two years following the hysterectomy, she experienced painful urination, fever, right abdominal pain, and right lower limb pain. CT and T2-weighed magnetic resonance imaging of her pelvis demonstrated right psoas abscess in conjunction with transplanted kidney. She was treated with broad-spectrum antibiotics alone, which resulted in a good response. Urinary obstruction of the transplanted kidney caused by uterine leiomyoma is an extremely rare condition. Psoas abscess secondary to transplanted kidney pyelonephritis is also rare. We should keep these rare diseases in mind when treating such cases. PMID:28097036

  2. [Oxidative stress: one of the major causes of vascular calcification in chronic kidney disease patients].

    PubMed

    Nyitrai, Mónika; Balla, György; Balla, József

    2015-11-22

    The leading cause of high mortality in dialyzed patients is cardiovascular disease. One of the main contributors of cardiovascular event is vascular calcification, which occurs even in very young patients. Multiple factors and complex mechanisms are involved in the formation of robust vascular calcification which affects a large vascular area observed in chronic kidney diseases. Patients on dialysis are exposed to enhanced oxidative stress as a result of increased pro-oxidant activity and reduced anti-oxidant systems. The oxidation of lipoprotein particles is implicated in the development of vascular damage representing oxidative threat, which leads to endothelial dysfunction. Moreover, in a pro-oxidant environment osteoblastic trans-differentiation of smooth muscle cells was shown to occur. Heme derived from oxidized hemoglobin might contribute to the formation of reactive lipid metabolites. This oxidative burden contributes to the development of atherosclerosis and vascular calcification. Heme oxygenase-1 and ferritin may serve as intracellular defense mechanisms against such an insult.

  3. A Kinetic Model for Cell Damage Caused by Oligomer Formation.

    PubMed

    Hong, Liu; Huang, Ya-Jing; Yong, Wen-An

    2015-10-06

    It is well known that the formation of amyloid fiber may cause invertible damage to cells, although the underlying mechanism has not been fully understood. In this article, a microscopic model considering the detailed processes of amyloid formation and cell damage is constructed based on four simple assumptions, one of which is that cell damage is raised by oligomers rather than mature fibrils. By taking the maximum entropy principle, this microscopic model in the form of infinite mass-action equations together with two reaction-convection partial differential equations (PDEs) has been greatly coarse-grained into a macroscopic system consisting of only five ordinary differential equations (ODEs). With this simple model, the effects of primary nucleation, elongation, fragmentation, and protein and seeds concentration on amyloid formation and cell damage have been extensively explored and compared with experiments. We hope that our results will provide new insights into the quantitative linkage between amyloid formation and cell damage.

  4. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products.

  5. Injury - kidney and ureter

    MedlinePlus

    Kidney damage; Toxic injury of the kidney; Kidney injury; Traumatic injury of the kidney; Fractured kidney; Inflammatory injury of the kidney; Bruised kidney; Ureteral injury; Pre-renal failure - injury, ...

  6. Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

    PubMed Central

    Villa, Luca; Buono, Roberta; Ferrandi, Mara; Molinari, Isabella; Benigni, Fabio; Bettiga, Arianna; Colciago, Giorgia; Ikehata, Masami; Messaggio, Elisabetta; Rastaldi, Maria Pia; Montorsi, Francesco; Salonia, Andrea; Manunta, Paolo

    2016-01-01

    Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO. PMID:27754425

  7. Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury.

    PubMed

    Villa, Luca; Buono, Roberta; Ferrandi, Mara; Molinari, Isabella; Benigni, Fabio; Bettiga, Arianna; Colciago, Giorgia; Ikehata, Masami; Messaggio, Elisabetta; Rastaldi, Maria Pia; Montorsi, Francesco; Salonia, Andrea; Manunta, Paolo

    2016-10-14

    Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2-3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.

  8. Bath Salts: A Newly Recognized Cause of Acute Kidney Injury

    PubMed Central

    McNeely, Jonathan; Parikh, Samir; Valentine, Christopher; Haddad, Nabil; Shidham, Ganesh; Rovin, Brad; Hebert, Lee; Agarwal, Anil

    2012-01-01

    Bath salts are substance of abuse that are becoming more common and are difficult to recognize due to negative toxicology screening. Acute kidney injury due to bath salt use has not previously been described. We present the case of a previously healthy male who developed acute kidney injury and dialysis dependence after bath salt ingestion and insufflation. This was self-reported with negative toxicology screening. Clinical course was marked by severe hyperthermia, hyperkalemia, rhabdomyolysis, disseminated intravascular coagulation, oliguria, and sepsis. We discuss signs and symptoms, differential diagnoses, potential mechanisms of injury, management, and review of the literature related to bath salt toxicity. PMID:24555135

  9. Oxidative Stress and DNA Damage Induced by Chromium in Liver and Kidney of Goldfish, Carassius auratus

    PubMed Central

    Velma, Venkatramreddy; Tchounwou, Paul B.

    2013-01-01

    Chromium (Cr) is an abundant element in the Earth’s crust. It exhibits various oxidation states, from divalent to hexavalent forms. Cr has diverse applications in various industrial processes and inadequate treatment of the industrial effluents leads to the contamination of the surrounding water resources. Hexavalent chromium (Cr (VI)) is the most toxic form, and its toxicity has been associated with oxidative stress. The present study was designed to investigate the toxic potential of Cr (VI) in fish. In this research, we investigated the role of oxidative stress in chromium-induced genotoxicity in the liver and kidney cells of goldfish, Carassius auratus. Goldfish were acclimatized to the laboratory conditions and exposed them to 5% and 10% of 96 hr-LC50 (85.7 mg/L) of aqueous Cr (VI) in a continuous flow through system. Fish were sampled every 7 days for a period of 28 days to analyze the lipid hydroperoxides (LHP) levels and genotoxic potentials in the liver and kidney. LHP levels were analyzed by spectrophotometry while genotoxicity was assessed by single cell gel electrophoresis (comet) assay. LHP levels in the liver increased significantly at week 1, followed by a decrease. LHP levels in the kidney increased significantly at weeks 1, 2, and 3, and decreased at week 4 compared to the control. The percentage of DNA damage increased in both liver and kidney at both test concentrations. The results clearly indicate that Cr (VI) induces significant levels of DNA damage in liver and kidney cells of goldfish. The induced LHP levels in both organs were concentration-dependent and were directly correlated with the levels of DNA damage. The two tested Cr (VI) concentrations induced significant levels of oxidative stress in both organs, however the kidney appears to be more vulnerable and sensitive to Cr-induced toxicity than the liver. PMID:23700361

  10. Excretory Function of Intestinal Tract Enhanced in Kidney Impaired Rats Caused by Adenine

    PubMed Central

    Yun, Yu; Gao, Tao; Li, Yue; Gao, Zhiyi; Duan, Jinlian; Yin, Hua

    2016-01-01

    The main aim of the study was to prove the compensative effect of intestine for renal function. Rat kidney was impaired by intragastrically administrating adenine (400 mg per day for 5 days). Intestinal tract was harvested and equally divided into 20 segments except cecum. Kidneys were harvested and histologically examined with hematoxylin-eosin staining kits. Uric acid, urea (BUN), and creatinine in serum were determined with assay kits, and BUN and creatinine in every intestinal segment were also determined. The results showed that adenine was able to increase uric acid level in serum from 20.98 ± 6.98 μg/mL to 40.77 ± 7.52 μg/mL and cause renal function damage with BUN (from 3.87 ± 0.62 mM to 12.33 ± 3.27 mM) and creatinine (from 51.48 ± 6.98 μM to 118.25 ± 28.63 μM) increasing in serum and with abnormally micromorphological changes in kidney. The amount of BUN and creatinine distributed in intestinal tract was positively correlated with those in blood. In impaired renal function rats, the amount of BUN (from 4.26 ± 0.21 μMole to 10.72 ± 0.55 μMole) and creatinine (from 681.4 ± 23.3 nMole to 928.7 ± 21.3 nMole) distributed in intestinal tract significantly increased. All the results proved that intestinal tract had excretory function compensative for renal function. PMID:27975080

  11. Hyperlipidemia-Associated Renal Damage Decreases Klotho Expression in Kidneys from ApoE Knockout Mice

    PubMed Central

    Sastre, Cristina; Rubio-Navarro, Alfonso; Buendía, Irene; Gómez-Guerrero, Carmen; Blanco, Julia; Mas, Sebastian; Egido, Jesús; Blanco-Colio, Luis Miguel; Ortiz, Alberto; Moreno, Juan Antonio

    2013-01-01

    Background Klotho is a renal protein with anti-aging properties that is downregulated in conditions related to kidney injury. Hyperlipidemia accelerates the progression of renal damage, but the mechanisms of the deleterious effects of hyperlipidemia remain unclear. Methods We evaluated whether hyperlipidemia modulates Klotho expression in kidneys from C57BL/6 and hyperlipidemic apolipoprotein E knockout (ApoE KO) mice fed with a normal chow diet (ND) or a Western-type high cholesterol-fat diet (HC) for 5 to 10 weeks, respectively. Results In ApoE KO mice, the HC diet increased serum and renal cholesterol levels, kidney injury severity, kidney macrophage infiltration and inflammatory chemokine expression. A significant reduction in Klotho mRNA and protein expression was observed in kidneys from hypercholesteromic ApoE KO mice fed a HC diet as compared with controls, both at 5 and 10 weeks. In order to study the mechanism involved in Klotho down-regulation, murine tubular epithelial cells were treated with ox-LDL. Oxidized-LDL were effectively uptaken by tubular cells and decreased both Klotho mRNA and protein expression in a time- and dose-dependent manner in these cells. Finally, NF-κB and ERK inhibitors prevented ox-LDL-induced Klotho downregulation. Conclusion Our results suggest that hyperlipidemia-associated kidney injury decreases renal expression of Klotho. Therefore, Klotho could be a key element explaining the relationship between hyperlipidemia and aging with renal disease. PMID:24386260

  12. Hypothyroidism causing paralytic ileus and acute kidney injury - case report

    PubMed Central

    2011-01-01

    We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit. Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far. It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications. PMID:21303532

  13. Hypothyroidism causing paralytic ileus and acute kidney injury - case report.

    PubMed

    Rodrigo, Chaturaka; Gamakaranage, Champika Sssk; Epa, Dhanesha S; Gnanathasan, Ariaranee; Rajapakse, Senaka

    2011-02-08

    We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit.Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far.It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications.

  14. Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

    NASA Astrophysics Data System (ADS)

    Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael; Motta, Mariana H.; Ribeiro, Roseane F.; dos S. Hausen, Bruna; Moresco, Rafael N.; Garcia, Solange C.; da Silva, Cristiane B.; Burger, Marilise E.

    2015-04-01

    Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups ( n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

  15. 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.

  16. Tissue damage in kidney, adrenal glands and diaphragm following extracorporeal shock wave lithotripsy.

    PubMed

    Gecit, Ilhan; Kavak, Servet; Oguz, Elif Kaval; Pirincci, Necip; Günes, Mustafa; Kara, Mikail; Ceylan, Kadir; Kaba, Mehmet; Tanık, Serhat

    2014-10-01

    This study was designed to investigate whether exposure to short-term extracorporeal shock wave lithotripsy (ESWL) produces histologic changes or induces apoptosis in the kidney, adrenal glands or diaphragm muscle in rats. The effect of shock waves on the kidney of male Wistar rats (n = 12) was investigated in an experimental setting using a special ESWL device. Animals were killed at 72 h after the last ESWL, and the tissues were stained with an in situ Cell Death Detection Kit, Fluorescein. Microscopic examination was performed by fluorescent microscopy. Apoptotic cell deaths in the renal tissue were not observed in the control group under fluorescent microscopy. In the ESWL group, local apoptotic changes were observed in the kidney in the area where the shock wave was focused. The apoptotic cell deaths observed in the adrenal gland of the control group were similar to those observed in the ESWL groups, and apoptosis was occasionally observed around the capsular structure. Apoptotic cell deaths in the diaphragm muscle were infrequently observed in the control group. Apoptosis in the ESWL group was limited to the mesothelial cells. This study demonstrated that serious kidney, adrenal gland and diaphragm muscles damage occurred following ESWL, which necessitated the removal of the organ in the rat model. It is recognized that the ESWL complications related to the kidney, adrenal gland and diaphragm muscles are rare and may be managed conservatively.

  17. Static cold storage preservation of ischemically damaged kidneys. a comparison between IGL-1 and UW solution.

    PubMed

    Maathuis, Mark-Hugo J; Ottens, Petra J; van Goor, Harry; Zwaagstra, Jacco J; Wiersema-Buist, Janneke; Schuurs, Theo A; Ploeg, Rutger J; Leuvenink, Henri G D

    2008-05-01

    Especially in damaged organs, adequate organ preservation is critically important to maintain viability. Institut Georges Lopez-1 (IGL-1) is a new preservation solution, with an extracellular sodium/potassium ratio and polyethylene glycol as a colloid. The influence of warm and cold ischemia was evaluated in a rat Lewis-Lewis transplant model with a follow up of 14 days. Eight groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0 and 15 min followed by 0- or 24-h cold storage (CS) preservation in IGL-1 or UW-CSS. Blood was collected daily during the first week and at day 14. Recipients were placed in metabolic cages at day 4 and 14 after transplantation allowing urine collection and adequate measurement of glomerular filtration rate. Focussing on inflammation, reactive oxygen species production, proximal tubule damage, proteinuria, histology, and renal function after transplantation we could not show any relevant difference between IGL-1 and UW-CSS. Furthermore, the combination of 15-min warm ischemia and by 24-h cold ischemia did not result in life sustaining kidney function after transplantation, irrespective of the used solution. In the present experiment, static CS preservation of ischemically damaged rat kidneys in either IGL-1 or UW-CSS rendered equal results after transplantation.

  18. Can graphene quantum dots cause DNA damage in cells?

    NASA Astrophysics Data System (ADS)

    Wang, Dan; Zhu, Lin; Chen, Jian-Feng; Dai, Liming

    2015-05-01

    Graphene quantum dots (GQDs) have attracted tremendous attention for biological applications. We report the first study on cytotoxicity and genotoxicity of GQDs to fibroblast cell lines (NIH-3T3 cells). The NIH-3T3 cells treated with GQDs at dosages over 50 μg mL-1 showed no significant cytotoxicity. However, the GQD-treated NIH-3T3 cells exhibited an increased expression of proteins (p53, Rad 51, and OGG1) related to DNA damage compared with untreated cells, indicating the DNA damage caused by GQDs. The GQD-induced release of reactive oxygen species (ROS) was demonstrated to be responsible for the observed DNA damage. These findings should have important implications for future applications of GQDs in biological systems.Graphene quantum dots (GQDs) have attracted tremendous attention for biological applications. We report the first study on cytotoxicity and genotoxicity of GQDs to fibroblast cell lines (NIH-3T3 cells). The NIH-3T3 cells treated with GQDs at dosages over 50 μg mL-1 showed no significant cytotoxicity. However, the GQD-treated NIH-3T3 cells exhibited an increased expression of proteins (p53, Rad 51, and OGG1) related to DNA damage compared with untreated cells, indicating the DNA damage caused by GQDs. The GQD-induced release of reactive oxygen species (ROS) was demonstrated to be responsible for the observed DNA damage. These findings should have important implications for future applications of GQDs in biological systems. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01734c

  19. Protective effect of dietary flaxseed oil on arsenic-induced nephrotoxicity and oxidative damage in rat kidney.

    PubMed

    Rizwan, Sana; Naqshbandi, Ashreeb; Farooqui, Zeba; Khan, Aijaz Ahmed; Khan, Farah

    2014-06-01

    Arsenic, a naturally occurring metalloid, is capable of causing acute renal failure as well as chronic renal insufficiency. Arsenic is known to exert its toxicity through oxidative stress by generating reactive oxygen species (ROS). Flaxseed, richest plant based dietary source of ω-3 polyunsaturated fatty acids (PUFAs) and lignans have shown numerous health benefits. Present study investigates the protective effect of flaxseed oil (FXO) on sodium arsenate (NaAs) induced renal damage. Rats prefed with experimental diets (Normal/FXO diet) for 14days, were administered NaAs (20mg/kg body weight i.p.) once daily for 4days while still on the experimental diets. NaAs nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. Administration of NaAs led to a significant decline in the specific activities of brush border membrane (BBM) enzymes both in kidney tissue homogenates and in the isolated membrane vesicles. Lipid peroxidation and total sulfhydryl groups were altered upon NaAs treatment, indicating the generation of oxidative stress. NaAs also decreased the activities of metabolic enzymes and antioxidant defence system. Histopathological studies supported the biochemical findings showing extensive damage to the kidney by NaAs. In contrast, dietary supplementation of FXO prior to and alongwith NaAs treatment significantly attenuated the NaAs-induced changes.

  20. Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans.

    PubMed

    Vivante, Asaf; Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hildebrandt, Friedhelm

    2014-04-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) cover a wide range of structural malformations that result from defects in the morphogenesis of the kidney and/or urinary tract. These anomalies account for about 40-50 % of children with chronic kidney disease worldwide. Knowledge from genetically modified mouse models suggests that single gene mutations in renal developmental genes may lead to CAKUT in humans. However, until recently, only a handful of CAKUT-causing genes were reported, most of them in familial syndromic cases. Recent findings suggest that CAKUT may arise from mutations in a multitude of different single gene causes. We focus here on single-gene causes of CAKUT and their developmental origin. Currently, more than 20 monogenic CAKUT-causing genes have been identified. High-throughput sequencing techniques make it likely that additional CAKUT-causing genes will be identified in the near future.

  1. 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.

  2. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    PubMed

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent.

  3. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice.

    PubMed

    Moyer, J H; Lee-Tischler, M J; Kwon, H Y; Schrick, J J; Avner, E D; Sweeney, W E; Godfrey, V L; Cacheiro, N L; Wilkinson, J E; Woychik, R P

    1994-05-27

    A line of transgenic mice was generated that contains an insertional mutation causing a phenotype similar to human autosomal recessive polycystic kidney disease. Homozygotes displayed a complex phenotype that included bilateral polycystic kidneys and an unusual liver lesion. The mutant locus was cloned and characterized through use of the transgene as a molecular marker. Additionally, a candidate polycystic kidney disease (PKD) gene was identified whose structure and expression are directly associated with the mutant locus. A complementary DNA derived from this gene predicted a peptide containing a motif that was originally identified in several genes involved in cell cycle control.

  4. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice

    SciTech Connect

    Moyer, J.H.; Lee-Tischler, M.J.; Kwon, H.Y.; Schrick, J.J. ); Avner, E.D.; Sweeney, W.E. ); Godfrey, V.L.; Cacheiro, N.L.A.; Woychik, R.P. ); Wilkinson, J.E. )

    1994-05-27

    A line of transgenic mice was generated that contains an insertional mutation causing a phenotype similar to human autosomal recessive polycystic kidney disease. Homozygotes displayed a complex phenotype that included bilateral polycystic kidneys and an unusual liver lesion. The mutant locus was cloned and characterized through use of the transgene as a molecular marker. Additionally, a candidate polycystic kidney disease (PKD) gene was identified whose structure and expression are directly associated with the mutant locus. A complementary DNA derived from this gene predicted a peptide containing a motif that was originally identified in several genes involved in cell cycle control.

  5. Enteric hyperoxaluria: an important cause of end-stage kidney disease.

    PubMed

    Nazzal, Lama; Puri, Sonika; Goldfarb, David S

    2016-03-01

    Hyperoxaluria is a frequent complication of inflammatory bowel diseases, ileal resection and Roux-en-Y gastric bypass and is well-known to cause nephrolithiasis and nephrocalcinosis. The associated prevalence of chronic kidney disease and end-stage kidney disease (ESKD) is less clear but may be more consequential than recognized. In this review, we highlight three cases of ESKD due to enteric hyperoxaluria following small bowel resections. We review current information on the pathophysiology, complications and treatment of this complex disease.

  6. Genetic susceptibility to hypertension-induced renal damage in the rat. Evidence based on kidney-specific genome transfer.

    PubMed Central

    Churchill, P C; Churchill, M C; Bidani, A K; Griffin, K A; Picken, M; Pravenec, M; Kren, V; St Lezin, E; Wang, J M; Wang, N; Kurtz, T W

    1997-01-01

    To test the hypothesis that genetic factors can determine susceptibility to hypertension-induced renal damage, we derived an experimental animal model in which two genetically different yet histocompatible kidneys are chronically and simultaneously exposed to the same blood pressure profile and metabolic environment within the same host. Kidneys from normotensive Brown Norway rats were transplanted into unilaterally nephrectomized spontaneously hypertensive rats (SHR-RT1.N strain) that harbor the major histocompatibility complex of the Brown Norway strain. 25 d after the induction of severe hypertension with deoxycorticosterone acetate and salt, proteinuria, impaired glomerular filtration rate, and extensive vascular and glomerular injury were observed in the Brown Norway donor kidneys, but not in the SHR-RT1.N kidneys. Control experiments demonstrated that the strain differences in kidney damage could not be attributed to effects of transplantation-induced renal injury, immunologic rejection phenomena, or preexisting strain differences in blood pressure. These studies (a) demonstrate that the kidney of the normotensive Brown Norway rat is inherently much more susceptible to hypertension-induced damage than is the kidney of the spontaneously hypertensive rat, and (b) establish the feasibility of using organ-specific genome transplants to map genes expressed in the kidney that determine susceptibility to hypertension-induced renal injury in the rat. PMID:9294102

  7. Bath salt intoxication causing acute kidney injury requiring hemodialysis.

    PubMed

    Regunath, Hariharan; Ariyamuthu, Venkatesh Kumar; Dalal, Pranavkumar; Misra, Madhukar

    2012-10-01

    Traditional bath salts contain a combination of inorganic salts like Epsom salts, table salt, baking soda, sodium metaphosphate, and borax that have cleansing properties. Since 2010, there have been rising concerns about a new type of substance abuse in the name of "bath salts." They are beta-ketone amphetamine analogs and are derivates of cathinone, a naturally occurring amphetamine analog found in the "khat" plant (Catha edulis). Effects reported with intake included increased energy, empathy, openness, and increased libido. Serious adverse effects reported with intoxication included cardiac, psychiatric, and neurological signs and symptoms. Not much is known about the toxicology and metabolism of these compounds. They inhibit monoamine reuptake (dopamine, nor epinephrine, etc.) and act as central nervous system stimulants with high additive and abuse potential because of their clinical and biochemical similarities to effects from use of cocaine, amphetamine, and 3,4-methylenedioxy-N-methylamphetamine. Deaths associated with use of these compounds have also been reported. We report a case of acute kidney injury associated with the use of "bath salt" pills that improved with hemodialysis.

  8. Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats.

    PubMed

    Han, Jing; Liang, Hua; Yi, Jianhua; Tan, Wuhong; He, Shulan; Wu, Xiaofang; Shi, Xiaowei; Ma, Jing; Guo, Xiong

    2016-03-01

    Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney.

  9. DNA damage in embryonic stem cells caused by nanodiamonds.

    PubMed

    Xing, Yun; Xiong, Wei; Zhu, Lin; Osawa, Eiji; Hussin, Saber; Dai, Liming

    2011-03-22

    Because of their unique photoluminescence and magnetic properties, nanodiamonds (NDs) are promising for biomedical imaging and therapeutical applications. However, these biomedical applications will hardly be realized unless the potential hazards of NDs to humans and other biological systems are ascertained. Previous studies performed in our group and others have demonstrated the excellent biocompatibility of NDs in a variety of cell lines without noticeable cytotoxicity. In the present paper, we report the first genotoxicity study on NDs. Our results showed that incubation of embryonic stem cells with NDs led to slightly increased expression of DNA repair proteins, such as p53 and MOGG-1. Oxidized nanodiamonds (O-NDs) were demonstrated to cause more DNA damage than the pristine/raw NDs (R-NDs), showing the surface chemistry specific genotoxicity. However, the DNA damages caused by either the O-NDs or the R-NDs are much less severe than those caused by multiwalled carbon nanotubes (MWNTs) observed in our previous study. These findings should have important implications for future applications of NDs in biological applications.

  10. Iatrogenic Damage to the Periodontium Caused by Periodontal Treatment Procedures

    PubMed Central

    Latheef, P; Sirajuddin, Syed; Gundapaneni, Veenadharini; MN, Kumuda; Apine, Ashwini

    2015-01-01

    Periodontitis is an inflammatory disease affecting the periodontium i.e. the tissues that surround and support the teeth. Periodontitis manifests as progressive loss of the alveolar bone around the teeth, and if left untreated, can cause loosening and subsequent loss of teeth. Periodontitis is initiated by microorganisms that adhere to and grow on the tooth's surfaces, besides an over -aggressive immune response against these microorganisms. The primary goal of periodontal therapy is to preserve the natural dentition by accomplishing and preserving a healthy functional periodontium. Many treatment modalities have been introduced to improve the therapeutic result of periodontal treatment which may also damage the periodontiumiatrogenically. PMID:26312087

  11. Associations among environmental exposure to manganese, neuropsychological performance, oxidative damage and kidney biomarkers in children.

    PubMed

    Nascimento, Sabrina; Baierle, Marília; Göethel, Gabriela; Barth, Anelise; Brucker, Natália; Charão, Mariele; Sauer, Elisa; Gauer, Bruna; Arbo, Marcelo Dutra; Altknecht, Louise; Jager, Márcia; Dias, Ana Cristina Garcia; de Salles, Jerusa Fumagalli; Saint' Pierre, Tatiana; Gioda, Adriana; Moresco, Rafael; Garcia, Solange Cristina

    2016-05-01

    Environmental exposure to manganese (Mn) results in several toxic effects, mainly neurotoxicity. This study investigated associations among Mn exposure, neuropsychological performance, biomarkers of oxidative damage and early kidney dysfunction in children aged 6-12 years old. Sixty-three children were enrolled in this study, being 43 from a rural area and 20 from an urban area. Manganese was quantified in blood (B-Mn), hair (H-Mn) and drinking water using inductively coupled plasma mass spectrometry (ICP-MS). The neuropsychological functions assessed were attention, perception, working memory, phonological awareness and executive functions - inhibition. The Intelligence quotient (IQ) was also evaluated. The biomarkers malondialdehyde (MDA), protein carbonyls (PCO), δ-aminolevulinate dehydratase (ALA-D), reactivation indexes with dithiothreitol (ALA-RE/DTT) and ZnCl2 (ALA-RE/ZnCl2), non-protein thiol groups, as well as microalbuminuria (mALB) level and N-acetyl-β-D-glucosaminidase (NAG) activity were assessed. The results demonstrated that Mn levels in blood, hair and drinking water were higher in rural children than in urban children (p<0.01). Adjusted for potential confounding factors, IQ, age, gender and parents' education, significant associations were observed mainly between B-Mn and visual attention (β=0.649; p<0.001). Moreover, B-Mn was negatively associated with visual perception and phonological awareness. H-Mn was inversely associated with working memory, and Mn levels from drinking water with written language and executive functions - inhibition. Rural children showed a significant increase in oxidative damage to proteins and lipids, as well as alteration in kidney function biomarkers (p<0.05). Moreover, significant associations were found between B-Mn, H-Mn and Mn levels in drinking water and biomarkers of oxidative damage and kidney function, besides between some oxidative stress biomarkers and neuropsychological tasks (p<0.05). The findings of this

  12. Disruption of IFT complex A causes cystic kidneys without mitotic spindle misorientation.

    PubMed

    Jonassen, Julie A; SanAgustin, Jovenal; Baker, Stephen P; Pazour, Gregory J

    2012-04-01

    Intraflagellar transport (IFT) complexes A and B build and maintain primary cilia. In the mouse, kidney-specific or hypomorphic mutant alleles of IFT complex B genes cause polycystic kidneys, but the influence of IFT complex A proteins on renal development is not well understood. In the present study, we found that HoxB7-Cre-driven deletion of the complex A gene Ift140 from collecting ducts disrupted, but did not completely prevent, cilia assembly. Mutant kidneys developed collecting duct cysts by postnatal day 5, with rapid cystic expansion and renal dysfunction by day 15 and little remaining parenchymal tissue by day 20. In contrast to many models of polycystic kidney disease, precystic Ift140-deleted collecting ducts showed normal centrosomal positioning and no misorientation of the mitotic spindle axis, suggesting that disruption of oriented cell division is not a prerequisite to cyst formation in these kidneys. Precystic collecting ducts had an increased mitotic index, suggesting that cell proliferation may drive cyst expansion even with normal orientation of the mitotic spindle. In addition, we observed significant increases in expression of canonical Wnt pathway genes and mediators of Hedgehog and tissue fibrosis in highly cystic, but not precystic, kidneys. Taken together, these studies indicate that loss of Ift140 causes pronounced renal cystic disease and suggest that abnormalities in several different pathways may influence cyst progression.

  13. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    PubMed

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.

  14. Modified halloysite nanotubes and the alleviation of kidney damage induced by dietary zearalenone in swine.

    PubMed

    Jia, Zhiqiang; Yin, Shutong; Liu, Min; Zhang, Yuanyuan; Gao, Rui; Shi, Baoming; Shan, Anshan; Chen, Zhihui

    2015-01-01

    The aims of this study were, first, to investigate the toxicity of zearalenone (ZEN) through the analysis of biochemical parameters, oxidative stress, pathological changes and inflammatory response in the kidney of gestation sows and offspring; and, second, to evaluate the efficacy of modified halloysite nanotubes (MHNTs) for the alleviation to the adverse effects induced by ZEN. This study focused on the period of organogenesis between days 35 and 70 of gestation, and treatments included (1) a control diet; (2) contaminated grain (50% control corn and 50% mouldy corn); and (3) contaminated grain (50% control corn and 50% mouldy corn) + 1% MHNTs. ZEN treatment significantly increased most of the biochemical parameters and inflammatory cytokines and degenerative changes in the kidney and induced oxidative damage in plasma, whereas the addition of MHNTs in combination with ZEN induced a re-establishment of the biochemical parameters, the plasma oxidative stress enzyme activities and the normal histology of the kidney. Thus, the data strongly suggest that the deleterious effects of ZEN can be significantly diminished by MHNTs.

  15. Osteopontin deficiency reduces kidney damage from hypercholesterolemia in Apolipoprotein E-deficient mice

    PubMed Central

    Pei, Zouwei; Okura, Takafumi; Nagao, Tomoaki; Enomoto, Daijiro; Kukida, Masayoshi; Tanino, Akiko; Miyoshi, Ken-ichi; Kurata, Mie; Higaki, Jitsuo

    2016-01-01

    Hypercholesterolemia is a well-established risk factor for kidney injury, which can lead to chronic kidney disease (CKD). Osteopontin (OPN) has been implicated in the pathology of several renal conditions. This study was to evaluate the effects of OPN on hypercholesterolemia induced renal dysfunction. Eight-week-old male mice were divided into 4 groups: apolipoprotein E knockout (ApoE−/−) and ApoE/OPN knockout (ApoE−/−/OPN−/−) mice fed a normal diet (ND) or high cholesterol diet (HD). After 4 weeks, Periodic acid-Schiff (PAS) and oil red O staining revealed excessive lipid deposition in the glomeruli of ApoE−/−HD mice, however, significantly suppressed in ApoE−/−/OPN−/−HD mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression was lower in the glomeruli of ApoE−/−/OPN−/−HD mice than ApoE−/−HD mice. In vitro study, primary mesangial cells were incubated with recombinant mouse OPN (rmOPN). RmOPN induced LOX-1 mRNA and protein expression in primary mesangial cells. Pre-treatment with an ERK inhibitor suppressed the LOX-1 gene expression induced by rmOPN. These results indicate that OPN contributes to kidney damage in hypercholesterolemia and suggest that inhibition of OPN may provide a potential therapeutic target for the prevention of hypercholesterolemia. PMID:27353458

  16. Monosodium glutamate-induced damage in liver and kidney: a morphological and biochemical approach.

    PubMed

    Ortiz, G G; Bitzer-Quintero, O K; Zárate, C Beas; Rodríguez-Reynoso, S; Larios-Arceo, F; Velázquez-Brizuela, I E; Pacheco-Moisés, F; Rosales-Corral, S A

    2006-02-01

    It has been demonstrated that high concentrations of monosodium glutamate in the central nervous system induce neuronal necrosis and damage in retina and circumventricular organs. In this model, the monosodium glutamate is used to induce an epileptic state; one that requires highly concentrated doses. The purpose of this study was to evaluate the toxic effects of the monosodium glutamate in liver and kidney after an intra-peritoneal injection. For the experiment, we used 192 Wistar rats to carry out the following assessments: a) the quantification of the enzymes alanine aminotransferase and aspartate aminotransferase, b) the quantification of the lipid peroxidation products and c) the morphological evaluation of the liver and kidney. During the experiment, all of these assessments were carried out at 0, 15, 30 and 45 min after the intra-peritoneal injection. In the rats that received monosodium glutamate, we observed increments in the concentration of alanine aminotransferase and aspartate aminotransferase at 30 and 45 min. Also, an increment of the lipid peroxidation products, in kidney, was exhibited at 15, 30 and 45 min while in liver it was observed at 30 and 45 min. Degenerative changes were observed (edema-degeneration-necrosis) at 15, 30 and 45 min.

  17. Kidney Cysts

    MedlinePlus

    ... common type of PKD end up with kidney failure. PKD also causes cysts in other parts of ... and lifestyle changes, and if there is kidney failure, dialysis or kidney transplants. Acquired cystic kidney disease ( ...

  18. Renal necrosis and DNA damage caused by selectively deuterated and methylated analogs of 1,2-dibromo-3-chloropropane in the rat

    SciTech Connect

    Omichinski, J.G.; Brunborg, G.; Soderlund, E.J.; Dahl, J.E.; Bausano, J.A.; Holme, J.A.; Nelson, S.D.; Dybing, E.

    1987-12-01

    Selectively deuterated and methylated analogs of the nematocide 1,2-dibromo-3-chloropropane (DBCP) were compared to DBCP in causing acute renal damage in rats. All of the six deuterated analogs tested at 340 mumol/kg, including the perdeutero compound, failed to significantly alter the kidney necrosis observed at 48 hr compared to DBCP. Furthermore, when the perdeutero analog was administered at several doses (42.5, 85, 170, and 340 mumol/kg), it caused kidney damage that was not significantly different than that caused by an equivalent molar dose of nondeuterated DBCP. Of the five methylated analogs tested at 170 and 340 mumol/kg, only C3-methyl-DBCP and 1,2-dibromo-4-chlorobutane caused nephrotoxicity. The C2-methyl-, C1-dimethyl-, and C2-methyl-DBCP analogs failed to cause renal necrosis determined 48 hr after dosing. In distribution studies DBCP, perdeutero-DBCP, and all the methylated analogs were found to concentrate in the kidney approximately 25 times relative to plasma 1 hr after administration. DBCP at doses of 4.3 mumol/kg and higher caused DNA damage in the kidney as early as 10 min after administration, as measured by alkaline elution of DNA from isolated kidney nuclear preparations. Perdeuteration did not decrease the DNA damaging effect of DBCP. The ability of the methylated DBCP analogs to induce renal DNA damage correlated with their necrogenic potential. Experiments using pretreatments that are known to decrease the nephrotoxicity caused by glutathione and cysteine conjugates of several halogenated alkenes were conducted to examine the effect of these pretreatments on DBCP-induced nephrotoxicity.

  19. [Star fruit as a cause of acute kidney injury].

    PubMed

    Scaranello, Karilla Lany; Alvares, Valeria Regina de Cristo; Carneiro, Daniely Maria Queiroz; Barros, Flávio Henrique Soares; Gentil, Thais Marques Sanches; Thomaz, Myriam José; Pereira, Benedito Jorge; Pereira, Mariana Batista; Leme, Graziella Malzoni; Diz, Mary Carla Esteves; Laranja, Sandra Maria Rodrigues

    2014-01-01

    The star fruit belongs to the family Oxalidacea, species Averrhoa carambola. It is rich in minerals, vitamin A, C, B complex vitamins and oxalic acid. Recent studies show that the toxicity of the fruit differs between the patients and may be explained by single biological responses, age, and the intake quantity of the neurotoxin in each fruit in addition to glomerular filtration rate given by each patient. Additionally, the nephrotoxicity caused by the fruit is dose-dependent and may lead to the deposition of crystals of calcium oxalate intratubular, as well as by direct injury to the renal tubular epithelium, leading to apoptosis of the same. We report the case of a patient who after ingestion of the juice and fresh fruit, developed acute renal failure requiring dialysis, evolving with favourable outcome and recovery of renal function.

  20. The effect of hypericum perforatum on kidney ischemia/reperfusion damage.

    PubMed

    Cakir, Murat; Duzova, Halil; Baysal, Işil; Gül, Cemile Ceren; Kuşcu, Gülbahar; Kutluk, Fatma; Çakin, Hilal; Şeker, Şifanur; İlbeği, Esranur; Uslu, Seda; Avci, Umut; Demir, Samet; Akinci, Cihan; Atli, Sercan

    2017-11-01

    It has been revealed in recent studies that Hypericum Perforatum (HP) is influential on cancer, inflammatory diseases, bacterial and viral diseases, and has neuroprotective and antioxidant properties. In this study, we investigated the effect of HP, which is known to have antioxidant and anti-inflammatory effects, on kidney I/R damage. Male Sprague-Dawley rats were divided into three groups, and each of the groups had eight rats: The Control Group; the Ischemia/Reperfusion (I/R) Group; and the IR + HP Group which was treated with 50 mg/kg of HP. The right kidneys of the rats were removed, and the left kidney developed ischemia during the 45th min, and reperfusion occurred in the following 3rd h. The histopathological findings and also the level of Malondialdehyde (MDA), Glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) enzyme activations in the renal tissues were measured. Blood Urea Nitrogen (BUN), Creatinin (Cre) from serum samples were determined. The levels of BUN, Cre, and kidney tissue MDA increased at a significant level, and the SOD, CAT, and GSH-PX enzyme activity decreased at a significant level in the I/R group, compared with the Control Group (p < 0.05). In the I/R + HP group, the levels of MDA decreased at a significant level compared to the I/R group, while the SOD, CAT, and GSH-PX activity increased (p < 0.05). In histopathological examinations, it was observed that the tubular dilatation and epithelial desquamation regressed in the IR + HP Group when compared with the I/R Group. It has been shown with the histological and biochemical results in this study that HP is protective against acute renal I/R.

  1. Climatology of damage-causing hailstorms over Germany

    NASA Astrophysics Data System (ADS)

    Kunz, M.; Puskeiler, M.; Schmidberger, M.

    2012-04-01

    In several regions of Central Europe, such as southern Germany, Austria, Switzerland, and northern Italy, hailstorms often cause substantial damage to buildings, crops, or automobiles on the order of several million EUR. In the federal state of Baden-Württemberg, for example, most of the insured damage to buildings is caused by large hailstones. Due to both their local-scale extent and insufficient direct monitoring systems, hail swaths are not captured accurately and uniquely by a single observation system. Remote-sensing systems such as radars are able to detect convection signals in a basic way, but they lack the ability to discern a clear relation between measured intensity and hail on the ground. These shortcomings hamper statistical analysis on the hail probability and intensity. Hail modelling thus is a big challenge for the insurance industry. Within the project HARIS-CC (Hail Risk and Climate Change), different meteorological observations are combined (3D / 2D radar, lightning, satellite and radiosounding data) to obtain a comprehensive picture of the hail climatology over Germany. The various approaches were tested and calibrated with loss data from different insurance companies between 2005 and 2011. Best results are obtained by considering the vertical distance between the 0°C level of the atmosphere and the echo top height estimated from 3D reflectivity data from the radar network of German Weather Service (DWD). Additionally, frequency, intensity, width, and length of hail swaths are determined by applying a cell tracking algorithm to the 3D radar data (TRACE3D; Handwerker, 2002). The hailstorm tracks identified are merged with loss data using a geographical information system (GIS) to verify damage-causing hail on the ground. Evaluating the hailstorm climatology revealed that hail probability exhibits high spatial variability even over short distances. An important issue is the spatial pattern of hail occurrence that is considered to be due to

  2. Resveratrol Protects Sepsis-Induced Oxidative DNA Damage in Liver and Kidney of Rats

    PubMed Central

    Aydın, Sevtap; Şahin, Tevfik Tolga; Bacanlı, Merve; Taner, Gökçe; Başaran, Arif Ahmet; Aydın, Mehtap; Başaran, Nurşen

    2016-01-01

    Background The increases of free radicals have been proposed to be involved in the pathogenesis of sepsis, which leads to multiple-organ dysfunction syndromes. The uses of antioxidants as a complementary tool in the medical care of oxidative stress-related diseases have attracted attention of researchers. Resveratrol (RV) has suggested being antioxidant, anti-proliferative, and anti-inflammatory effects in various experimental models and clinical settings. Aims This study was undertaken to evaluate the protective effects of RV on oxidative DNA damage induced by sepsis in the liver and kidney tissues of Wistar albino rats. Study Design Animal experimentation. Methods Four experimental groups consisting of eight animals for each was created using a total of thirty-two male Wistar albino rats. Sham group was given 0.5 mL of saline intra-peritoneal (ip) only following laparatomy. Sepsis group was given 0.5 mL saline ip only following the induction of sepsis. RV-treated group was given a dose of 100 mg/kg ip RV in 0.5 mL saline following laparatomy. RV-treated sepsis group was given 100 mg/kg ip RV in 0.5 mL saline following the induction of sepsis. A model of sepsis was created by cecal ligation and puncture technique. In the liver and kidney tissues, oxidative stress parameters (malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX)) and a proinflammatory cytokine (tumor necrosis factor alpha (TNF-alpha)), were evaluated spectrophotometrically and DNA damage was determined by the alkaline single cell gel electrophoresis (comet assay) technique using formamidopyrimidine DNA glycosylase protein. Results In the RV-treated sepsis group, the levels of MDA and TNF-alpha were lower and GSH levels, SOD and GPX activities were higher than in the septic rats (p<0.05). RV treatment significantly reduced the sepsis-induced oxidative DNA damage in the liver and kidney cells (p<0.05). Conclusion It is suggested that RV treatment

  3. Secreted Factors from Human Vestibular Schwannomas Can Cause Cochlear Damage

    PubMed Central

    Dilwali, Sonam; Landegger, Lukas D.; Soares, Vitor Y. R.; Deschler, Daniel G.; Stankovic, Konstantina M.

    2015-01-01

    Vestibular schwannomas (VSs) are the most common tumours of the cerebellopontine angle. Ninety-five percent of people with VS present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown. To establish the first model to study the role of VS-secreted factors in causing SNHL, murine cochlear explant cultures were treated with human tumour secretions from thirteen different unilateral, sporadic VSs of subjects demonstrating varied degrees of ipsilateral SNHL. The extent of cochlear explant damage due to secretion application roughly correlated with the subjects’ degree of SNHL. Secretions from tumours associated with most substantial SNHL resulted in most significant hair cell loss and neuronal fibre disorganization. Secretions from VSs associated with good hearing or from healthy human nerves led to either no effect or solely fibre disorganization. Our results are the first to demonstrate that secreted factors from VSs can lead to cochlear damage. Further, we identified tumour necrosis factor alpha (TNFα) as an ototoxic molecule and fibroblast growth factor 2 (FGF2) as an otoprotective molecule in VS secretions. Antibody-mediated TNFα neutralization in VS secretions partially prevented hair cell loss due to the secretions. Taken together, we have identified a new mechanism responsible for SNHL due to VSs. PMID:26690506

  4. Kidney Disease

    MedlinePlus

    ... version of this page please turn Javascript on. Kidney Disease What is Kidney Disease? What the Kidneys Do Click for more information You have two ... damaged, wastes can build up in the body. Kidney Function and Aging Kidney function may be reduced ...

  5. Iron-restricted pair-feeding affects renal damage in rats with chronic kidney disease

    PubMed Central

    Naito, Yoshiro; Senchi, Aya; Sawada, Hisashi; Oboshi, Makiko; Horimatsu, Tetsuo; Okuno, Keisuke; Yasumura, Seiki; Ishihara, Masaharu; Masuyama, Tohru

    2017-01-01

    Background We have previously shown that dietary iron restriction prevents the development of renal damage in a rat model of chronic kidney disease (CKD). However, iron deficiency is associated with appetite loss. In addition, calorie restriction is reported to prevent the development of end-stage renal pathology in CKD rats. Thus, the beneficial effect of iron restriction on renal damage may depend on calorie restriction. Here, we investigate the effect of pair-feeding iron restriction on renal damage in a rat model of CKD. Methods First, to determine the amount of food intake, Sprague-Dawley (SD) rats were randomly given an ad libitum normal diet or an iron-restricted diet, and the food intake was measured. Second, CKD was induced by a 5/6 nephrectomy in SD rats, and CKD rats were given either a pair-feeding normal or iron-restricted diet. Results Food intake was reduced in the iron-restricted diet group compared to the normal diet group of SD rats for 16 weeks (mean food intake; normal diet group and iron-restricted diet group: 25 and 20 g/day, respectively). Based on the initial experiments, CKD rats received either a pair-feeding normal or iron-restricted diet (20 g/day) for 16 weeks. Importantly, pair-feeding iron restriction prevented the development of proteinuria, glomerulosclerosis, and tubulointerstitial damage in CKD rats. Interestingly, pair-feeding iron restriction attenuated renal expression of nuclear mineralocorticoid receptor in CKD rats. Conclusions Pair-feeding iron restriction affected renal damage in a rat model of CKD. PMID:28196143

  6. Diabetic Kidney Problems

    MedlinePlus

    ... too high. Over time, this can damage your kidneys. Your kidneys clean your blood. If they are damaged, waste ... in your blood instead of leaving your body. Kidney damage from diabetes is called diabetic nephropathy. It ...

  7. Inhalation of mercury vapor can cause the toxic effects on rat kidney.

    PubMed

    Akgül, Nilgün; Altunkaynak, Berrin Zuhal; Altunkaynak, Muhammed Eyüp; Deniz, Ömür Gülsüm; Ünal, Deniz; Akgül, Hayati Murat

    2016-01-01

    Dental amalgam has been used in dentistry as a filling material. The filler comprises mercury (Hg). It is considered one of the most important and widespread environmental pollutants, which poses a serious potential threat for the humans and animals. However, mercury deposition affects the nervous, cardiovascular, pulmonary, gastrointestinal, and especially renal systems. In most animals' species and humans, the kidney is one of the main sites of deposition of mercury and target organ for its toxicity. In this study, the effects of mercury intake on kidney in rats were searched. For the this purpose; we used 24 adult female Wistar albino rats (200 g in weight) obtained from Experimental Research and Application Center of Atatürk University with ethical approval. Besides, they were placed into a specially designed glass cage. Along this experiment for 45 days, subjects were exposed to (1 mg/m(3)/day) mercury vapor. However, no application was used for the control subjects. At the end of the experiment, kidney samples were obtained from all subjects and processed for routine light microscopic level and stereological aspect were assessed. Finally, according to our results, mercury affects the histological features of the kidney. That means, the severe effects of mercury has been shown using stereological approach, which is one of the ideal quantitative methods in the current literature. In this study, it was detected that chronic exposure to mercury vapor may lead to renal damage and diseases in an experimental rat model.

  8. Malva sylvestris extract protects upon lithium carbonate-induced kidney damages in male rat.

    PubMed

    Ben Saad, Anouar; Rjeibi, Ilhem; Brahmi, Dalel; Smida, Amani; Ncib, Sana; Zouari, Nacim; Zourgui, Lazher

    2016-12-01

    Malva sylvestris has recently attracted special attention due to its potential activities in many chronic disorders. We aimed to assess the beneficial effects of Malva sylvestris extract against lithium carbonate induced renal damage in male Wistar rats. For this purpose, Malva sylvestris extract at a dose of 0.2g/kg was orally administrated, followed by 25mg/kg of lithium carbonate (intraperitoneal injection) for 30 days. Malva sylvestris extract was proved to contain large amounts of K(+), Na(+), Ca(++) and the existence of phenolic acids and flavonoids shown by the obtained HPLC-based analysis. The antioxidant capacities in vitro showed high level of radical scavenging activity and reducing power. The in vivo results showed that intraperitoneal injection of lithium carbonate exhibited a significant increase (p<0.01) of serum creatinine and urea and reduced serum sodium and potassium concentrations. Lithium carbonate also induced oxidative damage as indicated by a significant raise in LPO level associated with a decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in the kidney. However, pretreatment with Malva sylvestris extract restored the status of all parameters studied. It can be concluded that lithium carbonate has induced oxidative stress, biochemical changes and histopathological damage but the supplementation with Malva sylvestris extract has prevented such toxicity.

  9. Retention of acetylcarnitine in chronic kidney disease causes insulin resistance in skeletal muscle

    PubMed Central

    Miyamoto, Yasunori; Miyazaki, Teruo; Honda, Akira; Shimohata, Homare; Hirayama, Kouichi; Kobayashi, Masaki

    2016-01-01

    Insulin resistance occurs frequently in patients with chronic kidney disease. However, the mechanisms of insulin resistance associated with chronic kidney disease are unclear. It is known that an increase in the mitochondrial acetyl-CoA (AcCoA)/CoA ratio causes insulin resistance in skeletal muscle, and this ratio is regulated by carnitine acetyltransferase that exchanges acetyl moiety between CoA and carnitine. Because excess acetyl moiety of AcCoA is excreted in urine as acetylcarnitine, we hypothesized that retention of acetylcarnitine might be a cause of insulin resistance in chronic kidney disease patients. Serum acetylcarnitine concentrations were measured in chronic kidney disease patients, and were significantly increased with reduction of renal function. The effects of excess extracellular acetylcarnitine on insulin resistance were studied in cultured skeletal muscle cells (C2C12 and human myotubes), and insulin-dependent glucose uptake was significantly and dose-dependently inhibited by addition of acetylcarnitine. The added acetylcarnitine was converted to carnitine via reverse carnitine acetyltransferase reaction, and thus the AcCoA concentration and AcCoA/CoA ratio in mitochondria were significantly elevated. The results suggest that increased serum acetylcarnitine in CKD patients causes AcCoA accumulation in mitochondria by stimulating reverse carnitine acetyltransferase reaction, which leads to insulin resistance in skeletal muscle. PMID:27895387

  10. 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.

  11. Identification and isolation of kidney-derived stem cells from transgenic rats with diphtheria toxin-induced kidney damage

    PubMed Central

    Liu, Qing-Zhen; Chen, Xu-Dong; Liu, Gang; Guan, Guang-Ju

    2016-01-01

    Adult stem cells have been well characterized in numerous organs, with the exception of the kidneys. Therefore, the present study aimed to identify and isolate kidney-derived stem cells. A total of 12 Fischer 344 transgenic rats expressing the human diphtheria toxin receptor in podocyte cells of the kidney, were used in the present study. The rats were administered 5-bromo-2′-deoxyuridine (BrdU) in order to detect cellular proliferation. After 60 days, the rats were treated with the diphtheria toxin (DT), in order to induce kidney injury. Immunohistochemical analysis indicated that the number of BrdU-positive cells were increased following DT treatment. In addition, the expression of octamer-binding transcription factor 4 (Oct-4), a stem cell marker, was detected and suggested that kidney-specific stem cells were present in the DT-treated tissue samples. Furthermore, tissue samples exhibited repair of the DT-induced injury. Further cellular culturing was conducted in order to isolate the kidney-specific stem cells. After 5 weeks of culture, the majority of the cells were non-viable, with the exception of certain specialized, unique cell types, which were monomorphic and spindle-shaped in appearance. The unique cells were isolated and subjected to immunostaining and reverse transcription-polymerase chain reaction analyses in order to reconfirm the expression of Oct-4 and to detect the expression of Paired box 2 (Pax-2), which is necessary for the formation of kidney structures. The unique cells were positive for Oct-4 and Pax-2; thus suggesting that the identified cells were kidney-derived stem cells. The results of the present study suggested that the unique cell type identified in the kidneys of the DT-treated rats were kidney-specific stem cells that may have been involved in the repair of DT-induced tissue injury. In addition, these cells may provide a useful cell line for studying the fundamental characteristics of kidney stem cells, as well as identifying

  12. [Antiphospholipid syndrome in nephrology. Kidney damage and practical aspects of the management].

    PubMed

    Dekeyser, Manon; Zuily, Stéphane; Champigneulle, Jacqueline; Eschwège, Valérie; Frimat, Luc; Perret-Guillaume, Christine; Wahl, Denis

    2014-02-01

    The antiphospholipid syndrome is a thrombophilia characterized by the combination of arterial and/or venous thrombotic events or obstetric clinical events, associated with persistent presence of antiphospholipid antibodies. In this syndrome, thromboses may affect all of the vascular tree, renal damage is frequently associated with a specific antiphospholipid syndrome nephropathy. We propose in this review to provide updated recommendations on the management of antiphospholipid syndrome in nephrology. Treatment is based on long-term anticoagulant therapy with or without antiplatelet agents according to clinical events. The use of a conventional nephroprotection must not be forgotten (strict control of blood pressure with drugs blocking the renin-angiotensin-aldosterone system). Catastrophic antiphospholipid syndrome is an extremely severe complication which can threaten the vital prognosis of the patient. This justifies particular surveillance, as well as prevention in high-risk situations. We also illustrate the difficulties of long-term management in these patients, both in dialysis or kidney transplantation.

  13. 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.

  14. Characterization of kidney damage using several renal biomarkers in dogs with naturally occurring heatstroke.

    PubMed

    Segev, G; Daminet, S; Meyer, E; De Loor, J; Cohen, A; Aroch, I; Bruchim, Y

    2015-11-01

    Heatstroke is often associated with acute kidney injury (AKI). The objectives of this study were to characterize the kidney damage occurring in canine heatstroke using routine and novel biomarkers and to assess their diagnostic and prognostic performance. Thirty dogs with naturally occurring heatstroke were enrolled prospectively. Blood and urine specimens were collected at presentation, at 4 h post-presentation and every 12 h until discharge or death. The glomerular filtration rate (GFR) and electrolyte fractional excretion (FE) at 4 h post-presentation were also calculated, based on urinary clearances. AKI was further characterized by evaluating urine neutrophil gelatinase-associated lipocalin/creatinine ratio (UNGAL), urine retinol-binding protein/creatinine ratio (URBP), urine C-reactive protein/creatinine ratio (UCRP) and urine protein to creatinine ratio (UPC). These biomarkers were compared to those for 13 healthy dogs. Thirteen dogs (43%) died and 17 (57%) survived. Median serum creatinine concentration at presentation was 1.69 mg/dL (range, 0.5-4.7 mg/dL), while concurrent GFR was markedly decreased (median 0.60 mL/min/kg; range, 0.00-3.10 mL/min/kg). Median Na fractional excretion was 0.08 (range, 0.01-0.41) and was an accurate predictor of AKI (area under curve 0.89; 95% confidence intervals 0.76-1.00). Median UPC at presentation was 4.8 (range, 0.4-46.0). Median UCRP, URBP and UNGAL were increased in all dogs with heatstroke, and were mean 232, 133, and 1213-fold higher than healthy control dogs, respectively. In conclusion, although AKI occurs invariably in dogs with heatstroke, it is often subclinical at presentation. Damage occurs in both the renal tubules and the glomeruli. Novel kidney function tests for the characterization of renal injury and its severity are superior to conventional markers and could be used to facilitate early diagnosis of AKI.

  15. Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women

    SciTech Connect

    Barregard, Lars; Bergström, Göran; Fagerberg, Björn

    2014-11-15

    Background: It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim: To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods: All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results: The mean B-Cd (n=590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg Alb/12 h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT

  16. Protective effects of berberine on high fat-induced kidney damage by increasing serum adiponectin and promoting insulin sensitivity.

    PubMed

    Wu, Ueyue; Cha, Ying; Huang, Xinmei; Liu, Jun; Chen, Zaoping; Wang, Fang; Xu, Jiong; Sheng, Li; Ding, Heyuan

    2015-01-01

    Berberine (BBR) has been reported in several studies in cell and animal models. However, the mechanism of actions is not fully understood. The present study was therefore aimed to explore the effects of berberine on insulin sensitivity and kidney damage in a high fat diet rat model. Impaired glucose tolerance rats induced by injection of berberine while fed with high fat laboratory chow. After rats were treated for 4 weeks, OGTT and IPITT were determined. Mass and PAS were used to study the kidney tissue. ELISA was used to detect the protein concentration of CRP and TNF-α. Western blot was used to detect the proteins adiponectin, adipoR1, adipoR2 and p-AMPK expression level. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent kidney damage.

  17. Identification of microRNA biomarker candidates in urine and plasma from rats with kidney or liver damage

    PubMed Central

    Shah, Pooja; Sano, Tomoya; Shinozawa, Tadahiro; Bernard, Hugues; Gallacher, Matt J.; Wyllie, Shylah D.; Varrone, Georgianna; Cicia, Lisa A.; Carsillo, Mary E.; Fisher, Craig D.; Ottinger, Sean E.; Koenig, Erik; Kirby, Patrick J.

    2016-01-01

    Abstract MicroRNAs (miRNA) are short single‐stranded RNA sequences that have a role in the post‐transcriptional regulation of genes. The identification of tissue specific or enriched miRNAs has great potential as novel safety biomarkers. One longstanding goal is to associate the increase of miRNA in biofluids (e.g., plasma and urine) with tissue‐specific damage. Next‐generation sequencing (miR‐seq) was used to analyze changes in miRNA profiles of tissue, plasma and urine samples of rats treated with either a nephrotoxicant (cisplatin) or one of two hepatotoxicants (acetaminophen [APAP] or carbon tetrachloride [CCL4]). Analyses with traditional serum chemistry and histopathology confirmed that toxicant‐induced organ damage was specific. In animals treated with cisplatin, levels of five miRNAs were significantly altered in the kidney, 14 in plasma and six in urine. In APAP‐treated animals, five miRNAs were altered in the liver, 74 in plasma and six in urine; for CCL4 the changes were five, 20 and 6, respectively. Cisplatin treatment caused an elevation of miR‐378a in the urine, confirming the findings of other similar studies. There were 17 in common miRNAs elevated in the plasma after treatment with either APAP or CCL4. Four of these (miR‐122, −802, −31a and −365) are known to be enriched in the livers of rats. Interestingly, the increase of serum miR‐802 in both hepatotoxicant treatments was comparable to that of the well‐known liver damage marker miR‐122. Taken together, comparative analysis of urine and plasma miRNAs demonstrated their utility as biomarkers of organ injury. Copyright © 2016 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. PMID:27397436

  18. Reversal of Mitochondrial Damage Caused by Environmental Neurotoxins

    DTIC Science & Technology

    1999-10-01

    on electron transport and respiration of mitochondria. In turn, damage to mitochondria can contribute to the progression of Parkinson’s disease and...leads concerning thiol redox status (viz., oxidation of GSH, formation of PrSSG) can lead to improved methods to protect DA neurons from damage by environmental neurotoxins or from the ravages of Parkinson’s disease .

  19. Reversal of Mitochondrial Damage Caused by Environmental Neurotoxins

    DTIC Science & Technology

    2000-10-01

    the progression of Parkinson’s disease and to the damaging effects of environmental neurotoxins. In year 1, we showed that MAO suppressed respiration...that reverse damage, can lead to improved methods to protect DA neurons from environmental neurotoxins and from the ravages of Parkinson’s disease .

  20. Hydronephrosis in the Wnt5a-ablated kidney is caused by an abnormal ureter-bladder connection.

    PubMed

    Yun, Kangsun; Perantoni, Alan O

    The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme. The conditional mutants fail to form a normal renal medulla but no longer exhibit duplex kidney formation. Approximately 1/3 of the mutants develop hydronephrosis in the kidneys either uni- or bilaterally when using Dll1Cre. The abnormal kidney phenotype becomes prominent at E16.5, which approximates the time when urine production begins in the mouse embryonic kidney, and is associated with a dramatic increase in apoptosis only in mutant kidneys with hydronephrosis. Methylene blue dye injection and histologic examination reveal that aberrant cell death likely results from urine toxicity due to an abnormal ureter-bladder connection. This study shows that Wnt5a is not required for development of the renal medulla and that loss of the renal medullary region in the Wnt5a-deleted kidney is caused by an abnormal ureter-bladder connection.

  1. Plumb as a cause of kidney cancer (case study: Iran from 2008-2010)

    PubMed Central

    Mazdak, Hamid; Rashidi, Maasoumeh; Zohary, Moien

    2015-01-01

    Background: The main threats to human health from heavy metals are associated with exposure to plumb (Pb), cadmium, mercury, and arsenic. Some hazards that threat human health are the results of environmental factors and the relevant pollutions. Some important categories of diseases including (cancers) have considerable differences in various places, as observed in their spatial prevalence and distribution maps. The present study sets out to investigate the correlation between kidney cancer and the concentration of Pb in Iran. Materials and Methods: In this study, the first challenge was to collect some relevant information. In this connection, the authors managed to gain access to data concerning kidney cancer in Iran. The data were collected by a health centre for the period of 2008-2010. Besides, a map of Pb distribution in soil, drawn by the Mineral Exploration Organization, and Plumb Concentration Information, collected by Agriculture Jihad Organization, were used. Using a geographic information system (GIS) software such as ArcGIS (USA), the researchers drew the map of the spatial distribution of kidney cancer in the Iran country. In the indirect methods, one measures vegetation stress caused by heavy metal soil contamination. In direct methods, target detection algorithms are used to detect a selected material on the basis of its unique spectral signature. In this research, we applied target detection algorithms on moderate resolution imaging spectroradiometer (MODIS) images to detect Pb. MODIS is a sensor placed on the Terra satellite that collects data in 35 spectral bands with 250-1,000 m special resolutions. Results: The spatial distribution of kidney cancer in Iran country delineated above revealed a positive correlation between the amount of lead and the high frequency of kidney cancer. Regression analyses also confirmed this relationship (R2 = 0.77 and R = 0.87). Conclusion: The findings of the current study underscore not only the importance of

  2. Hydatid Disease Involved in the Heart, Liver, and Kidney That Caused Sudden Death: Case Report.

    PubMed

    Daş, Taner; Özer, Mehmet; Yağmur, Gülhan; Yildirim, Muzaffer; Özgün, Ayşe; Demirel, Hüsrev

    2015-12-01

    Hydatid disease is a parasitic infestation caused by ingestion of eggs of echinococcal species. For Echinococcus granulosus, the definitive host is the dog, and sheeps are the usual intermediate hosts. Humans are accidental intermediate hosts, infected by ingestion of food contaminated with eggs shed by dogs or foxes. The most common organs that hydatid disease encountered are the liver and lungs. Involvement of the kidney is rare and usually accompanies the other organ involvements. Cardiac involvement of echinococcosis is also very rare. We report the case of a 31-year-old woman with a 6-year history of asthma who collapsed after strenuous activity and died despite the interventions carried out. At autopsy, cystic masses were detected in the apex of the heart, in the right kidney, and in the liver. There were no macroscopic pathologic findings in the other organs. Microscopic examination revealed the diagnosis of hydatid cyst in the heart, right kidney, and liver besides medial hypertrophy of the lung vessels. Cause of death was attributed to hydatid cyst and its complications. Patients who have symptoms akin to asthma at clinical presentation have to be further investigated for organic cardiac and pulmonary diseases such as hydatid cyst, especially in endemic countries.

  3. Northridge earthquake damage caused by geologic focusing of seismic waves

    PubMed

    Davis; Rubinstein; Liu; Gao; Knopoff

    2000-09-08

    Despite being located 21 kilometers from the epicenter of the 1994 Northridge earthquake (magnitude 6.7), the city of Santa Monica experienced anomalously concentrated damage with Mercalli intensity IX, an intensity as large as that experienced in the vicinity of the epicenter. Seismic records from aftershocks suggest that the damage resulted from the focusing of seismic waves by several underground acoustic lenses at depths of about 3 kilometers, formed by the faults that bound the northwestern edge of the Los Angeles basin. The amplification was greatest for high-frequency waves and was less powerful at lower frequencies, which is consistent with focusing theory and finite-difference simulations.

  4. Markers of endothelial damage in patients with chronic kidney disease on hemodialysis.

    PubMed

    Carmona, Andrés; Agüera, Maria L; Luna-Ruiz, Carlos; Buendía, Paula; Calleros, Laura; García-Jerez, Andrea; Rodríguez-Puyol, Manuel; Arias, Manuel; Arias-Guillen, Marta; de Arriba, Gabriel; Ballarin, Jose; Bernis, Carmen; Fernández, Elvira; García-Rebollo, Sagrario; Mancha, Javier; Del Peso, Gloria; Pérez, Estefanía; Poch, Esteban; Portolés, Jose M; Rodríguez-Puyol, Diego; Sánchez-Villanueva, Rafael; Sarro, Felipe; Torres, Armando; Martín-Malo, Alejandro; Aljama, Pedro; Ramírez, Rafael; Carracedo, Julia

    2017-04-01

    Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD14(2+)/CD16(+), CD14(+)/CD16(2+)) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14(+)/CD16(2+) and CD14(2+)/CD16(+)), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

  5. Kidney Failure

    MedlinePlus

    Healthy kidneys clean your blood by removing excess fluid, minerals, and wastes. They also make hormones that keep your ... strong and your blood healthy. But if the kidneys are damaged, they don't work properly. Harmful ...

  6. Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae.

    PubMed

    Doudican, Nicole A; Song, Binwei; Shadel, Gerald S; Doetsch, Paul W

    2005-06-01

    Mitochondria contain their own genome, the integrity of which is required for normal cellular energy metabolism. Reactive oxygen species (ROS) produced by normal mitochondrial respiration can damage cellular macromolecules, including mitochondrial DNA (mtDNA), and have been implicated in degenerative diseases, cancer, and aging. We developed strategies to elevate mitochondrial oxidative stress by exposure to antimycin and H(2)O(2) or utilizing mutants lacking mitochondrial superoxide dismutase (sod2Delta). Experiments were conducted with strains compromised in mitochondrial base excision repair (ntg1Delta) and oxidative damage resistance (pif1Delta) in order to delineate the relationship between these pathways. We observed enhanced ROS production, resulting in a direct increase in oxidative mtDNA damage and mutagenesis. Repair-deficient mutants exposed to oxidative stress conditions exhibited profound genomic instability. Elimination of Ntg1p and Pif1p resulted in a synergistic corruption of respiratory competency upon exposure to antimycin and H(2)O(2). Mitochondrial genomic integrity was substantially compromised in ntg1Delta pif1Delta sod2Delta strains, since these cells exhibit a total loss of mtDNA. A stable respiration-defective strain, possessing a normal complement of mtDNA damage resistance pathways, exhibited a complete loss of mtDNA upon exposure to antimycin and H(2)O(2). This loss was preventable by Sod2p overexpression. These results provide direct evidence that oxidative mtDNA damage can be a major contributor to mitochondrial genomic instability and demonstrate cooperation of Ntg1p and Pif1p to resist the introduction of lesions into the mitochondrial genome.

  7. Root cause analysis of limitations of virtual crossmatch for kidney allocation to highly-sensitized patients.

    PubMed

    Jani, Vivek; Ingulli, Elizabeth; Mekeel, Kristen; Morris, Gerald P

    2017-02-01

    Efficient allocation of deceased donor organs depends upon effective prediction of immunologic compatibility based on donor HLA genotype and recipient alloantibody profile, referred to as virtual crossmatching (VCXM). VCXM has demonstrated utility in predicting compatibility, though there is reduced efficacy for patients highly sensitized against allogeneic HLA antigens. The recently revised deceased donor kidney allocation system (KAS) has increased transplantation for this group, but with an increased burden for histocompatibility testing and organ sharing. Given the limitations of VCXM, we hypothesized that increased organ offers for highly-sensitized patients could result in a concomitant increase in offers rejected due to unexpectedly positive crossmatch. Review of 645 crossmatches performed for deceased donor kidney transplantation at our center did not reveal a significant increase in positive crossmatches following KAS implementation. Positive crossmatches not predicted by VCXM were concentrated among highly-sensitized patients. Root cause analysis of VCXM failures identified technical limitations of anti-HLA antibody testing as the most significant contributor to VCXM error. Contributions of technical limitations including additive/synergistic antibody effects, prozone phenomenon, and antigens not represented in standard testing panels, were evaluated by retrospective testing. These data provide insight into the limitations of VCXM, particularly those affecting allocation of kidneys to highly-sensitized patients.

  8. Proteomic and phosphoproteomic analysis of renal cortex in a salt-load rat model of advanced kidney damage

    PubMed Central

    Jiang, Shaoling; He, Hanchang; Tan, Lishan; Wang, Liangliang; Su, Zhengxiu; Liu, Yufeng; Zhu, Hongguo; Zhang, Menghuan; Hou, Fan Fan; Li, Aiqing

    2016-01-01

    Salt plays an essential role in the progression of chronic kidney disease and hypertension. However, the mechanisms underlying pathogenesis of salt-induced kidney damage remain largely unknown. Here, Sprague-Dawley rats, that underwent 5/6 nephrectomy (5/6Nx, a model of advanced kidney damage) or sham operation, were treated for 2 weeks with a normal or high-salt diet. We employed aTiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for proteomic and phosphoproteomic profiling of the renal cortex. We found 318 proteins differentially expressed in 5/6Nx group relative to sham group, and 310 proteins significantly changed in response to salt load in 5/6Nx animals. Totally, 1810 unique phosphopeptides corresponding to 550 phosphoproteins were identified. We identified 113 upregulated and 84 downregulated phosphopeptides in 5/6Nx animals relative to sham animals. Salt load induced 78 upregulated and 91 downregulated phosphopeptides in 5/6Nx rats. The differentially expressed phospholproteins are important transporters, structural molecules, and receptors. Protein-protein interaction analysis revealed that the differentially phosphorylated proteins in 5/6Nx group, Polr2a, Srrm1, Gsta2 and Pxn were the most linked. Salt-induced differential phosphoproteins, Myh6, Lmna and Des were the most linked. Altered phosphorylation levels of lamin A and phospholamban were validated. This study will provide new insight into pathogenetic mechanisms of chronic kidney disease and salt sensitivity. PMID:27775022

  9. DNA Damage in Embryonic Stem Cells Caused by Nanodiamonds

    DTIC Science & Technology

    2011-03-03

    have important implications for future applications of NDs in biological applications . KEYWORDS: nanodiamond . DNA damage . embryonic stem cells... Application of Single Fluorescent Nanodiamonds as Cellular Biomarkers. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 727–732. 7. Vial, S.; Mansuy, C.; Sagan...S.; Pozdnyakova, I. O.; Puzyr, A. P. Applications of Nanodiamonds for Separation and Purification of Proteins. Phys. Solid State 2004, 46, 758–760

  10. Magnolia Extract (BL153) Ameliorates Kidney Damage in a High Fat Diet-Induced Obesity Mouse Model

    PubMed Central

    Cui, Wenpeng; Wang, Yangwei; Chen, Qiang; Sun, Weixia; Cai, Lu; Tan, Yi; Kim, Ki-Soo; Kim, Ki Ho; Kim, Young Heui

    2013-01-01

    Accumulating evidence demonstrated that obesity is a risk factor for renal structural and functional changes, leading to the end-stage renal disease which imposes a heavy economic burden on the community. However, no effective therapeutic method for obesity-associated kidney disease is available. In the present study, we explored the therapeutic potential of a magnolia extract (BL153) for treating obesity-associated kidney damage in a high fat diet- (HFD-) induced mouse model. The results showed that inflammation markers (tumor necrosis factor-α and plasminogen activator inhibitor-1) and oxidative stress markers (3-nitrotyrosine and 4-hydroxy-2-nonenal) were all significantly increased in the kidney of HFD-fed mice compared to mice fed with a low fat diet (LFD). Additionally, proteinuria and renal structure changes in HFD-fed mice were much more severe than that in LFD-fed mice. However, all these alterations were attenuated by BL153 treatment, accompanied by upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and hexokinase II (HK II) expression in the kidney. The present study indicates that BL153 administration may be a novel approach for renoprotection in obese individuals by antiinflammation and anti-oxidative stress most likely via upregulation of PGC-1α and HK II signal in the kidney. PMID:24381715

  11. Phycobiliproteins or C-phycocyanin of Arthrospira (Spirulina) maxima protect against HgCl(2)-caused oxidative stress and renal damage.

    PubMed

    Rodríguez-Sánchez, R; Ortiz-Butrón, R; Blas-Valdivia, V; Hernández-García, A; Cano-Europa, E

    2012-12-15

    Our objective was to determine if the phycobiliproteins of Arthrospira (Spirulina) maxima protect renal cells against mercury-caused oxidative stress and cellular damage in the kidney. We used 40 male mice that were assigned into eight groups: (1) a control group that received 100mM phosphate buffer (PB) ig and 0.9% saline ip, (2) PB+HgCl(2) (5mg/kg ip), (3) PB plus phycobiliproteins (100mg/kg ig), (4) PB plus C-phycocyanin (100mg/kg ig), and four groups receiving HgCl(2)+phycobiliproteins or C-phycocyanin (50, and 100mg/kg ig). The left kidneys were used to determine lipid peroxidation, quantification of reactive oxygen species, and reduced glutathione and oxidised content. The right kidneys were processed for histology. The HgCl(2) caused oxidative stress and cellular damage. All doses of phycobiliproteins or C-phycocyanin prevented enhancement of oxidative markers and they protected against HgCl(2)-caused cellular damage.

  12. HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney Disease.

    PubMed

    Chen, Zhiyong; Migeon, Tiffany; Verpont, Marie-Christine; Zaidan, Mohamad; Sado, Yoshikazu; Kerjaschki, Dontscho; Ronco, Pierre; Plaisier, Emmanuelle

    2016-04-01

    Hereditary angiopathy, nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant syndrome caused by mutations in COL4A1 that encodes the α1 chain of collagen IV, a major component of basement membranes. Patients present with cerebral small vessel disease, retinal tortuosity, muscle cramps, and kidney disease consisting of multiple renal cysts, chronic kidney failure, and sometimes hematuria. Mutations producing HANAC syndrome localize within the integrin binding site containing CB3[IV] fragment of the COL4A1 protein. To investigate the pathophysiology of HANAC syndrome, we generated mice harboring the Col4a1 p.Gly498Val mutation identified in a family with the syndrome. Col4a1 G498V mutation resulted in delayed glomerulogenesis and podocyte differentiation without reduction of nephron number, causing albuminuria and hematuria in newborns. The glomerular defects resolved within the first month, but glomerular cysts developed in 3-month-old mutant mice. Abnormal structure of Bowman's capsule was associated with metalloproteinase induction and activation of the glomerular parietal epithelial cells that abnormally expressed CD44,α-SMA, ILK, and DDR1. Inflammatory infiltrates were observed around glomeruli and arterioles. Homozygous Col4a1 G498V mutant mice additionally showed dysmorphic papillae and urinary concentration defects. These results reveal a developmental role for the α1α1α2 collagen IV molecule in the embryonic glomerular basement membrane, affecting podocyte differentiation. The observed association between molecular alteration of the collagenous network in Bowman's capsule of the mature kidney and activation of parietal epithelial cells, matrix remodeling, and inflammation may account for glomerular cyst development and CKD in patients with COL4A1-related disorders.

  13. Ionization damage in NPN transistors caused by lower energy electrons

    NASA Astrophysics Data System (ADS)

    Li, Xingji; Xiao, Jingdong; Liu, Chaoming; Zhao, Zhiming; Geng, Hongbin; Lan, Mujie; Yang, Dezhuang; He, Shiyu

    2010-09-01

    Electrical degradation of two type NPN bipolar junction transistors (BJTs) with different emitter sizes was examined under exposures of 70 and 110 keV electrons. Base and collector currents as a function of base-emitter voltage were in-situ measured during exposure. Experimental results show that both the 70 and 110 keV electrons produce an evident ionization damage to the NPN BJTs. With increasing fluence, collector currents of the NPN BJTs hardly change in the whole range of base-emitter voltage from 0 to 1.2 V, while base currents increase in a gradually mitigative trend. Base currents vary more at lower base-emitter voltages than at higher ones for a given fluence. The change in the reciprocal of current gain at a fixed base-emitter voltage of 0.65 V increases non-linearly at lower fluences and tends to be gradually saturated at higher fluences. Sensitivity to ionization damage increases for BJTs with an emitter having a larger perimeter-to-area ratio.

  14. Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function.

    PubMed

    Guebre-Egziabher, Fitsum; Alix, Pascaline M; Koppe, Laetitia; Pelletier, Caroline C; Kalbacher, Emilie; Fouque, Denis; Soulage, Christophe O

    2013-11-01

    Ectopic lipid accumulation is now known to be a mechanism that contributes to organ injury in the context of metabolic diseases. In muscle and liver, accumulation of lipids impairs insulin signaling. This hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, aging and lipodystrophy. Increasing data suggest that lipid accumulation in the kidneys could also contribute to the alteration of kidney function in the context of metabolic syndrome and obesity. Furthermore and more unexpectedly, animal models of kidney disease exhibit a decreased adiposity and ectopic lipid redistribution suggesting that kidney disease may be a state of lipodystrophy. However, whether this abnormal lipid partitioning during chronic kidney disease (CKD) may have any functional impact in these tissues needs to be investigated. Here, we provide a perspective by defining the problem and analyzing the possible causes and consequences. Further human studies are required to strengthen these observations, and provide novel therapeutic approaches.

  15. Exome Sequencing Frequently Reveals the Cause of Early-Onset Chronic Kidney Disease

    PubMed Central

    Vivante, Asaf; Hildebrandt, Friedhelm

    2016-01-01

    The primary causes of chronic kidney disease (CKD) in children differ from those of adult onset CKD. In the United States the most common diagnostic groups of CKD that manifests before 25 years of age are: i) congenital anomalies of the kidneys and urinary tract (CAKUT) (49.1%), ii) steroid-resistant nephrotic syndrome (SRNS) (10.4%), iii) chronic glomerulonephritis (8.1%), and iv) renal cystic ciliopathies (5.3 %), encompassing >70% of CKD together. Recent findings suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. High-throughput sequencing has very recently rendered identification of causative mutations in this high number of genes feasible. Molecular genetic diagnostics in early onset-CKD (before the age of 25 years) will, i) provide patients and families with a molecular genetic diagnosis, ii) generate new insights into diseases mechanisms, iii) allow etiology-based classification of patient cohorts for clinical studies and, iv) may have consequences for personalized treatment and prevention of CKD. In this review, we will discuss the implications of next-generation sequencing for clinical genetic diagnostics and discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and therapeutic implications. PMID:26750453

  16. Exposure to benzene metabolites causes oxidative damage in Saccharomyces cerevisiae.

    PubMed

    Raj, Abhishek; Nachiappan, Vasanthi

    2016-06-01

    Hydroquinone (HQ) and benzoquinone (BQ) are known benzene metabolites that form reactive intermediates such as reactive oxygen species (ROS). This study attempts to understand the effect of benzene metabolites (HQ and BQ) on the antioxidant status, cell morphology, ROS levels and lipid alterations in the yeast Saccharomyces cerevisiae. There was a reduction in the growth pattern of wild-type cells exposed to HQ/BQ. Exposure of yeast cells to benzene metabolites increased the activity of the anti-oxidant enzymes catalase, superoxide dismutase and glutathione peroxidase but lead to a decrease in ascorbic acid and reduced glutathione. Increased triglyceride level and decreased phospholipid levels were observed with exposure to HQ and BQ. These results suggest that the enzymatic antioxidants were increased and are involved in the protection against macromolecular damage during oxidative stress; presumptively, these enzymes are essential for scavenging the pro-oxidant effects of benzene metabolites.

  17. Thirdhand smoke causes DNA damage in human cells.

    PubMed

    Hang, Bo; Sarker, Altaf H; Havel, Christopher; Saha, Saikat; Hazra, Tapas K; Schick, Suzaynn; Jacob, Peyton; Rehan, Virender K; Chenna, Ahmed; Sharan, Divya; Sleiman, Mohamad; Destaillats, Hugo; Gundel, Lara A

    2013-07-01

    Exposure to thirdhand smoke (THS) is a newly described health risk. Evidence supports its widespread presence in indoor environments. However, its genotoxic potential, a critical aspect in risk assessment, is virtually untested. An important characteristic of THS is its ability to undergo chemical transformations during aging periods, as demonstrated in a recent study showing that sorbed nicotine reacts with the indoor pollutant nitrous acid (HONO) to form tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The goal of this study was to assess the genotoxicity of THS in human cell lines using two in vitro assays. THS was generated in laboratory systems that simulated short (acute)- and long (chronic)-term exposures. Analysis by liquid chromatography-tandem mass spectrometry quantified TSNAs and common tobacco alkaloids in extracts of THS that had sorbed onto cellulose substrates. Exposure of human HepG2 cells to either acute or chronic THS for 24h resulted in significant increases in DNA strand breaks in the alkaline Comet assay. Cell cultures exposed to NNA alone showed significantly higher levels of DNA damage in the same assay. NNA is absent in freshly emitted secondhand smoke, but it is the main TSNA formed in THS when nicotine reacts with HONO long after smoking takes place. The long amplicon-quantitative PCR assay quantified significantly higher levels of oxidative DNA damage in hypoxanthine phosphoribosyltransferase 1 (HPRT) and polymerase β (POLB) genes of cultured human cells exposed to chronic THS for 24h compared with untreated cells, suggesting that THS exposure is related to increased oxidative stress and could be an important contributing factor in THS-mediated toxicity. The findings of this study demonstrate for the first time that exposure to THS is genotoxic in human cell lines.

  18. Protective effect of green tea extract against proline-induced oxidative damage in the rat kidney.

    PubMed

    Delwing-Dal Magro, Débora; Roecker, Roberto; Junges, Gustavo M; Rodrigues, André F; Delwing-de Lima, Daniela; da Cruz, José G P; Wyse, Angela T S; Pitz, Heloisa S; Zeni, Ana L B

    2016-10-01

    We investigated, in vivo (acute and chronic), the effects of proline on thiobarbituric acid-reactive substances (TBA-RS) and on the activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in renal tissues (cortex and medulla) of rats. For acute administration, 29-day-old rats received a single subcutaneous injection of proline (18.2μmol/g body weight) or an equivalent volume of 0.9% saline solution and were sacrificed 1h later. For chronic treatment, proline was injected subcutaneously in the rats twice a day from the 6th to the 28th day of age, and the animals were killed 12h after the last injection. The results showed that acute administration of proline enhanced CAT, SOD and GSH-Px activities, as well as, TBARS in the cortex and decreased CAT activity in the medulla, while chronic treatment increased the activities of SOD in the cortex and increased CAT, SOD and GSH-Px in the medulla of rats. Furthermore, the green tea extract treatment for one week or from the 6th to the 28th day of age prevented the alterations caused by acute and chronic, respectively, proline administration. Herein, we demonstrated that proline alters antioxidant defenses and induces lipid peroxidation in the kidney of rats and the green tea extract was capable to counteract the proline-induced alterations.

  19. Rotator Cuff Damage: Reexamining the Causes and Treatments.

    ERIC Educational Resources Information Center

    Nash, Heyward L.

    1988-01-01

    Sports medicine specialists are beginning to reexamine the causes and treatments of rotator cuff problems, questioning the role of primary impingement in a deficient or torn cuff and trying new surgical procedures as alternatives to the traditional open acromioplasty. (Author/CB)

  20. Solastalgia: living with the environmental damage caused by natural disasters.

    PubMed

    Warsini, Sri; Mills, Jane; Usher, Kim

    2014-02-01

    Forced separation from one's home may trigger emotional distress. People who remain in their homes may experience emotional distress due to living in a severely damaged environment. These people experience a type of 'homesickness' similar to nostalgia because the land around them no longer resembles the home they knew and loved. What they lack is solace or comfort from their home; they long for the home environment to be the way it was before. "Solastalgia" is a term created to describe feelings which arise in people when an environment changes so much that it negatively affects an individual's quality of life. Such changed environments may include drought-stricken areas and open-cut mines. The aim of this article is to describe how solastalgia, originally conceptualized as the result of man-made environmental change, can be similarly applied to the survivors of natural disasters. Using volcanic eruptions as a case example, the authors argue that people who experience a natural disaster are likely to suffer from solastalgia for a number of reasons, which may include the loss of housing, livestock and farmland, and the ongoing danger of living in a disaster-prone area. These losses and fears challenge people's established sense of place and identity and can lead to feelings of helplessness and depression.

  1. Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase.

    PubMed Central

    Baker, G L; Corry, R J; Autor, A P

    1985-01-01

    Superoxide anion free radical (O2-.) has been implicated in the pathogenesis of tissue injury consequent to ischemia/reperfusion in several different organs, including heart and bowel. Superoxide dismutase (SOD), an enzyme free radical scavenger specific for O2-., has been used successfully to protect these organs from structural damage during reoxygenation of ischemic tissue. It has been suggested that the catalytic action of xanthine oxidase in injured tissue is an important source of O2-. during reoxygenation. In order to evaluate the potential of SOD to protect against kidney damage resulting from transient ischemia followed by reperfusion with oxygenated blood, a model of warm renal ischemia was studied. LBNF1 rats underwent right nephrectomy and occlusion of the left renal artery for 45 minutes. Survival in the group of ischemic untreated rats (N = 30) was 56% at 7 days and serum creatinine was greatly elevated (p less than 0.01) in rats remaining alive over the full 7-day period. In strong contrast to these results, all of the animals treated with SOD before reperfusion (N = 18) were alive after 7 days similar to sham operated control rats (N = 8). Serum creatinine in the SOD treated rats was significantly elevated only to postoperative day 3 and thereafter returned to normal. Rats treated with inactive SOD (N = 4) or SOD before ischemia (N = 4) had decreased survival rates compared to ischemic untreated animals and prolonged elevation of serum creatinine. When the ischemia time was extended to 60 minutes, only 19% of the untreated animals (N = 16) survived at 7 days whereas nearly 60% of the SOD-treated animals survived (N = 19). Serum creatinine was greatly elevated during the full 7-day observation period in all surviving rats in the untreated ischemic group, whereas serum creatinine returned to normal (p less than 0.05) after 4 days in the surviving rats treated with SOD. To test whether the action of xanthine oxidase contributed to the kidney damage

  2. TLR4-mediated inflammation is a key pathogenic event leading to kidney damage and fibrosis in cyclosporine nephrotoxicity.

    PubMed

    González-Guerrero, Cristian; Cannata-Ortiz, Pablo; Guerri, Consuelo; Egido, Jesús; Ortiz, Alberto; Ramos, Adrián M

    2017-04-01

    Cyclosporine A (CsA) successfully prevents allograft rejection, but nephrotoxicity is still a dose-limiting adverse effect. TLR4 activation promotes kidney damage but whether this innate immunity receptor mediates CsA nephrotoxicity is unknown. The in vivo role of TLR4 during CsA nephrotoxicity was studied in mice co-treated with CsA and the TLR4 inhibitor TAK242 and also in TLR4(-/-) mice. CsA-induced renal TLR4 expression in wild-type mice. Pharmacological or genetic targeting of TLR4 reduced the activation of proinflammatory signaling, including JNK/c-jun, JAK2/STAT3, IRE1α and NF-κB and the expression of Fn14. Expression of proinflammatory factors and cytokines was also decreased, and kidney monocyte and lymphocyte influx was prevented. TLR4 inhibition also reduced tubular damage and drastically prevented the development of kidney fibrosis. In vivo and in vitro CsA promoted secretion of the TLR ligand HMGB1 by tubular cells upstream of TLR4 activation, and prevention of HMGB1 secretion significantly reduced CsA-induced synthesis of MCP-1, suggesting that HMGB1 may be one of the mediators of CsA-induced TLR4 activation. These results suggest that TLR4 is a potential pharmacological target in CsA nephrotoxicity.

  3. Comparison of myocardial damage among dogs at different stages of clinical leishmaniasis and dogs with idiopathic chronic kidney disease.

    PubMed

    Martínez-Hernández, L; Casamian-Sorrosal, D; Barrera-Chacón, R; Cuesta-Gerveno, J M; Belinchón-Lorenzo, S; Gómez Nieto, L C; Duque-Carrasco, F J

    2017-03-01

    Canine leishmaniasis (CanL) is a systemic disease caused by the protozoan parasite Leishmania infantum. Myocarditis in CanL has been described previously in CanL by histopathological analysis of post-mortem specimens and by evaluation of cardiac troponin I (cTnI) levels. However, the degree of myocardial damage at different stages of CanL and the role that concurrent azotaemia plays in this myocardial injury are unknown. The aim of this study was to prospectively evaluate and compare the presence of myocardial injury in dogs at different stages of clinical CanL and in dogs with severe idiopathic chronic kidney disease (CKD) by measuring cTnI. Forty-eight dogs were included in the study, divided into four groups: (1) group A (10 healthy dogs); (2) group B (17 dogs with CanL without renal azotaemia, classified as mild to severe in the LeishVet scheme); (3) group C (11 dogs with CanL and renal azotaemia, classified as very severe in the LeishVet scheme); and (4) group D (10 dogs with idiopathic CKD). Dogs in group C had significantly higher cTnI than dogs in groups B and D, although cTnI was also elevated in these groups. Dogs in group A had normal cTnI values. Dogs in groups D and C had similar renal IRIS classification scorers. Severe lymphoplasmocytic myocarditis and a positive real time PCR of L. infantum DNA were observed in all dogs in group C. Dogs with very severe CanL exhibit more myocardial injury than dogs with milder CanL or dogs with idiopathic CKD.

  4. Understanding transportation-caused rangeland damage in Mongolia.

    PubMed

    Keshkamat, S S; Tsendbazar, N E; Zuidgeest, M H P; Shiirev-Adiya, S; van der Veen, A; van Maarseveen, M F A M

    2013-01-15

    Mongolia, a vast and sparsely populated semi-arid country, has very little formal road infrastructure. Since the 1990s, private ownership and usage of vehicles has been increasing, which has created a web of dirt track corridors due to the communal land tenure and unobstructed terrain, with some of these corridors reaching over 4 km in width. This practice aids wind- and water-aided erosion and desertification, causing enormous negative environmental effects. Little is being done to counter the phenomenon, mainly because the logic of the driving behaviour that causes this dirt road widening is not fully understood. The research in this article postulates that this driving behaviour has rational foundations and is linked to various geographical factors (natural and man-made geographical features). We analysed 11,000 km of arterial routes in the country using spatial statistics and determined that geographically weighted regression (GWR) analysis offers a good explanation for whether, and by how much, the selected geographical factors affect the creation of corridor widths and how their effect varies across the landscape. We determined that corridor widths are correlated to factors such as proximity to river crossings, traffic intensity, and vegetation abundance. Knowing these factors can help local planners and engineers design counter-measures that could help to control and reduce the widths of these corridors, until paved roads can replace the dirt track corridors.

  5. INFLUENCE OF EXPERIMENTAL KIDNEY DAMAGE ON HISTOCHEMICALLY DEMONSTRABLE LIPASE ACTIVITY IN THE RAT. COMPARISON WITH ALKALINE PHOSPHATASE ACTIVITY

    PubMed Central

    Wachstein, M.

    1946-01-01

    Lipase activity was found in the cytoplasm of the proximal convoluted tubules in tissue sections of rat, rabbit, dog, mouse, hamster, and guinea pig, stained according to Gomori's method. Uranium and mercury poisoning do not inactivate the enzyme in necrotic cells of the proximal convoluted tubules. Its activity diminished in the atrophic and regenerating cells of the kidneys of rats, surviving the acute phase of the intoxication. In the acute stage of choline deficiency marked reduction in enzymatic activity was seen in the necrotic tubules, and in the atrophied and regenerating tubules in the subacute stage. Lipase activity was markedly diminished in hydronephrotic kidneys 10 to 12 days after ligation of the ureter. In sections stained for alkaline phosphatase activity nearly identical alterations were found. Experimental damage influences both histochemically demonstrable enzymes in a similar manner. PMID:19871551

  6. Pure red cell aplasia caused by Parvo B19 virus in a kidney transplant recipient.

    PubMed

    Baral, A; Poudel, B; Agrawal, R K; Hada, R; Gurung, S

    2012-01-01

    Parvo B19 is a single stranded DNA virus, which typically has affinity for erythroid progenitor cells in the bone marrow and produces a severe form of anemia known as pure red cell aplasia. This condition is particularly worse in immunocompromised individuals. We herein report a young Nepali male who developed severe and persistent anaemia after kidney transplantation while being on immunosuppressive therapy. His bone marrow examination revealed morphological changes of pure red cell aplasia, caused by parvovirus B19. The IgM antibody against the virus was positive and the virus was detected by polymerase chain reaction in the blood. He was managed with intravenous immunoglobulin. He responded well to the treatment and has normal hemoglobin levels three months post treatment. To the best of our knowledge, this is the first such case report from Nepal.

  7. Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2.

    PubMed

    Cabezas, Oscar Rubio; Flanagan, Sarah E; Stanescu, Horia; García-Martínez, Elena; Caswell, Richard; Lango-Allen, Hana; Antón-Gamero, Montserrat; Argente, Jesús; Bussell, Anna-Marie; Brandli, Andre; Cheshire, Chris; Crowne, Elizabeth; Dumitriu, Simona; Drynda, Robert; Hamilton-Shield, Julian P; Hayes, Wesley; Hofherr, Alexis; Iancu, Daniela; Issler, Naomi; Jefferies, Craig; Jones, Peter; Johnson, Matthew; Kesselheim, Anne; Klootwijk, Enriko; Koettgen, Michael; Lewis, Wendy; Martos, José María; Mozere, Monika; Norman, Jill; Patel, Vaksha; Parrish, Andrew; Pérez-Cerdá, Celia; Pozo, Jesús; Rahman, Sofia A; Sebire, Neil; Tekman, Mehmet; Turnpenny, Peter D; Hoff, William Van't; Viering, Daan H H M; Weedon, Michael N; Wilson, Patricia; Guay-Woodford, Lisa; Kleta, Robert; Hussain, Khalid; Ellard, Sian; Bockenhauer, Detlef

    2017-04-03

    Hyperinsulinemic hypoglycemia (HI) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders. The co-occurrence of these disorders (HIPKD) in 17 children from 11 unrelated families suggested an unrecognized genetic disorder. Whole-genome linkage analysis in five informative families identified a single significant locus on chromosome 16p13.2 (logarithm of odds score 6.5). Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, we found in all patients a promoter mutation (c.-167G>T) in the phosphomannomutase 2 gene (PMM2), either homozygous or in trans with PMM2 coding mutations. PMM2 encodes a key enzyme in N-glycosylation. Abnormal glycosylation has been associated with PKD, and we found that deglycosylation in cultured pancreatic β cells altered insulin secretion. Recessive coding mutations in PMM2 cause congenital disorder of glycosylation type 1a (CDG1A), a devastating multisystem disorder with prominent neurologic involvement. Yet our patients did not exhibit the typical clinical or diagnostic features of CDG1A. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2 We propose that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. Our findings extend the spectrum of genetic causes for both HI and PKD and provide insights into gene regulation and PMM2 pleiotropy.

  8. The cosmetic dye quinoline yellow causes DNA damage in vitro.

    PubMed

    Chequer, Farah Maria Drumond; Venâncio, Vinícius de Paula; de Souza Prado, Maíra Rocha; Campos da Silva e Cunha Junior, Luiz Raimundo; Lizier, Thiago Mescoloto; Zanoni, Maria Valnice Boldrin; Rodríguez Burbano, Rommel; Bianchi, Maria Lourdes Pires; Antunes, Lusânia Maria Greggi

    2015-01-01

    Quinoline yellow (QY) is a chinophthalon derivative used in cosmetic compositions for application to the skin, lips, and/or body surface. However, regulatory data about the genotoxicity and/or mutagenicity of this compound are still controversial. Therefore, this work evaluated the genotoxicity of QY using the comet assay and the cytokinesis-block micronucleus cytome assay (CBMN-Cyt) in the metabolically competent cell line HepG2, which closely mimics phase I metabolism. This research also identified the products formed after electrochemical oxidation of the QY dye, which simulates hepatic biotransformation. The primary products generated after the oxidation process were analyzed by High Performance Liquid Chromatography coupled with a Diode Array Detector (HPLC/DAD), which detected the production of 4,4'-diaminodiphenylmethane, 2-methoxy-5-methylaniline and 4,4'-oxydianiline. The results demonstrated that low (from 0.5 to 20 μg mL(-1)) QY concentrations were genotoxic in HepG2 cells on both assays and those harmful compounds were detected after the oxidation process. Our findings suggest that this colorant could cause harmful effects to humans if it is metabolized or absorbed through the skin.

  9. 78 FR 41991 - Pipeline Safety: Potential for Damage to Pipeline Facilities Caused by Flooding

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Potential for Damage to Pipeline Facilities Caused by Flooding AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA); DOT... operators should contact the appropriate state pipeline safety authority. A list of state pipeline...

  10. Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome.

    PubMed

    Mollet, Géraldine; Ratelade, Julien; Boyer, Olivia; Muda, Andrea Onetti; Morisset, Ludivine; Lavin, Tiphaine Aguirre; Kitzis, David; Dallman, Margaret J; Bugeon, Laurence; Hubner, Norbert; Gubler, Marie-Claire; Antignac, Corinne; Esquivel, Ernie L

    2009-10-01

    Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial and sporadic forms of steroid-resistant nephrotic syndrome. In mice, constitutive absence of podocin leads to rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis and nephrotic syndrome. Using established Cre-loxP technology, we inactivated podocin in the adult mouse kidney in a podocyte-specific manner. Progressive loss of podocin in the glomerulus recapitulated albuminuria, hypercholesterolemia, hypertension, and renal failure seen in nephrotic syndrome in humans. Lesions of FSGS appeared after 4 wk, with subsequent development of diffuse glomerulosclerosis and tubulointerstitial damage. Interestingly, conditional inactivation of podocin at birth resulted in a gradient of glomerular lesions, including mesangial proliferation, demonstrating a developmental stage dependence of renal histologic patterns of injury. The development of significant albuminuria in this model occurred only after early and focal foot process effacement had progressed to diffuse involvement, with complete absence of podocin immunolabeling at the slit diaphragm. Finally, we identified novel potential mediators and perturbed molecular pathways, including cellular proliferation, in the course of progression of renal disease leading to glomerulosclerosis, using global gene expression profiling.

  11. Podocin Inactivation in Mature Kidneys Causes Focal Segmental Glomerulosclerosis and Nephrotic Syndrome

    PubMed Central

    Mollet, Géraldine; Ratelade, Julien; Boyer, Olivia; Muda, Andrea Onetti; Morisset, Ludivine; Lavin, Tiphaine Aguirre; Kitzis, David; Dallman, Margaret J.; Bugeon, Laurence; Hubner, Norbert; Gubler, Marie-Claire; Esquivel, Ernie L.

    2009-01-01

    Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial and sporadic forms of steroid-resistant nephrotic syndrome. In mice, constitutive absence of podocin leads to rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis and nephrotic syndrome. Using established Cre-loxP technology, we inactivated podocin in the adult mouse kidney in a podocyte-specific manner. Progressive loss of podocin in the glomerulus recapitulated albuminuria, hypercholesterolemia, hypertension, and renal failure seen in nephrotic syndrome in humans. Lesions of FSGS appeared after 4 wk, with subsequent development of diffuse glomerulosclerosis and tubulointerstitial damage. Interestingly, conditional inactivation of podocin at birth resulted in a gradient of glomerular lesions, including mesangial proliferation, demonstrating a developmental stage dependence of renal histologic patterns of injury. The development of significant albuminuria in this model occurred only after early and focal foot process effacement had progressed to diffuse involvement, with complete absence of podocin immunolabeling at the slit diaphragm. Finally, we identified novel potential mediators and perturbed molecular pathways, including cellular proliferation, in the course of progression of renal disease leading to glomerulosclerosis, using global gene expression profiling. PMID:19713307

  12. Methanol exposure does not produce oxidatively damaged DNA in lung, liver or kidney of adult mice, rabbits or primates

    SciTech Connect

    McCallum, Gordon P.; Siu, Michelle; Sweeting, J. Nicole; Wells, Peter G.

    2011-01-15

    In vitro and in vivo genotoxicity tests indicate methanol (MeOH) is not mutagenic, but carcinogenic potential has been claimed in one controversial long-term rodent cancer bioassay that has not been replicated. To determine whether MeOH could indirectly damage DNA via reactive oxygen species (ROS)-mediated mechanisms, we treated male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys with MeOH (2.0 g/kg ip) and 6 h later assessed oxidative damage to DNA, measured as 8-oxo-2'-deoxyguanosine (8-oxodG) by HPLC with electrochemical detection. We found no MeOH-dependent increases in 8-oxodG in lung, liver or kidney of any species. Chronic treatment of CD-1 mice with MeOH (2.0 g/kg ip) daily for 15 days also did not increase 8-oxodG levels in these organs. These results were corroborated in DNA repair-deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice, which accumulated 8-oxodG in lung, kidney and liver with age, but exhibited no increase following MeOH, despite a 2-fold increase in renal 8-oxodG in Ogg1 KO mice following treatment with a ROS-initiating positive control, the renal carcinogen potassium bromate (KBrO{sub 3}; 100 mg/kg ip). These observations suggest that MeOH exposure does not promote the accumulation of oxidatively damaged DNA in lung, kidney or liver, and that environmental exposure to MeOH is unlikely to initiate carcinogenesis in these organs by DNA oxidation.

  13. Brief communication "The assessment of damage caused by historical landslide events"

    NASA Astrophysics Data System (ADS)

    Petrucci, O.

    2013-03-01

    The paper presents a methodology for relative damage assessment for historical landslide events, i.e. periods during which damage caused by rainfall-triggered landslides affected wide areas. The approach requires a minimum amount of data, and it is based on the assessment of direct, indirect and intangible damage indices at municipal and regional scale. An application to major events which occurred in Calabria (Italy) highlighted roads as the most vulnerable element, even representing the source of intangible damage for people forced to use alternative roads for their daily activities. Indirect costs seem mainly tied to displacement of people even for short periods.

  14. A case of acetaminophen (paracetamol) causing renal failure without liver damage in a child and review of literature.

    PubMed

    Ozkaya, Ozan; Genc, Gurkan; Bek, Kenan; Sullu, Yurdanur

    2010-01-01

    Acetaminophen (paracetamol) is a widely used drug and known as a safety antipyretic and analgesic drug in childhood. Acetaminophen-associated liver damage is more recognized than kidney damage. Nephrotoxicity and hepatotoxicity can be seen together after acetaminophen overdose, but renal damage without liver damage is a rarely seen entity in all age groups being reported more rarely in childhood. We present here a 16-year-old girl with renal failure without liver damage because of acetaminophen toxicity and a review of literature for pathophysiological mechanisms, clinical course, treatment, and outcome.

  15. Causes of forest damage in Europe: Major hypotheses and factors. [Picea rubens; Abies balsmea; Abies fraseri

    SciTech Connect

    Prinz, B. )

    1987-11-01

    Forest damage has become a major topic of public and scientific discussion in recent years. Significant controversy has developed regarding the causes of this damage. This is especially true in West Germany (Federal Republic of Germany), where forests are considered in both economic and emotional terms. The mythic bonds between man and forest go back into ancient history. This article first explains the difference between the novel character of recent forest damage and the classic form of smoke damage. The different forms of forest damage in Central Europe and North America are then compared, and evidence for and against several hypotheses of causation of chlorosis, or yellowing, of evergreen needles at upper elevations - the most important type of forest damage in Germany - is discussed in detail.

  16. Hyperactivation of Akt/mTOR and deficiency in tuberin increased the oxidative DNA damage in kidney cancer patients with diabetes.

    PubMed

    Habib, Samy L; Liang, Sitai

    2014-05-15

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have explored one of the mechanisms by which diabetes accelerates tumorigenesis in the kidney. Kidney cancer tissue from patients with diabetes showed a higher activity of Akt and decreased in total protein of tuberin compared to kidney cancer patient without diabetes or diabetes alone. In addition, a significant increase in phospho-Akt/tuberin expression was associated with an increase in Ki67 expression and activation of mTOR in kidney tumor with or without diabetes compared to diabetes alone. In addition, decrease in tuberin expression resulted in a significant decrease in protein expression of OGG1 and increased in oxidative DNA damage, 8-oxodG in kidney tissues from patients with cancer or cancer+diabetes. Importantly, these data showed that the majority of the staining of Akt/tuberin/p70S6K phosphorylation was more prominently in the tubular cells. In addition, accumulation of oxidative DNA damage is localized only in the nucleus of tubular cells within the cortex region. These data suggest that Akt/tuberin/mTOR pathway plays an important role in the regulation DNA damage and repair pathways that may predispose diabetic kidneys to pathogenesis of renal cell carcinoma.

  17. Comparison of damage to human hair fibers caused by monoethanolamine- and ammonia-based hair colorants.

    PubMed

    Bailey, Aaron D; Zhang, Guiru; Murphy, Bryan P

    2014-01-01

    The number of Level 3 hair color products that substitute 2-aminoethanol [monoethanolamine (MEA)] for ammonia is increasing. There is some anecdotal evidence that higher levels of MEA can be more damaging to hair and more irritating than a corresponding equivalent level of the typical alkalizer, ammonia (in the form of ammonium hydroxide). Our interest was to understand in more quantitative terms the relative hair damage from the two alkalizers, particularly at the upper limits of MEA on-head use. Limiting investigations of oxidative hair damage to increases in cysteic acid content (from cystine oxidation) can underreport the extent of total damage. Hence, we complemented Fourier transform infrared spectroscopy (FTIR) cysteic acid level measurement with scanning electron microscopy (SEM) photomicrographs to visualize cuticle damage, and protein loss to understand not only the oxidative damage but also the damage caused by other damage pathways, e.g., reaction of the more nucleophilic (than ammonia) MEA with hair protein. In fact, all methods show an increase in damage from MEA-based formulations, up to 85% versus ammonia in the most extreme case. Hence, if the odor of ammonia is a concern, a better approach may be to minimize the volatility of ammonia in specific chassis rather than replacing it with high levels of a potentially more damaging alkalizer such as MEA.

  18. The protective effects of Prunus armeniaca L (apricot) against methotrexate-induced oxidative damage and apoptosis in rat kidney.

    PubMed

    Vardi, Nigar; Parlakpinar, Hakan; Ates, Burhan; Cetin, Asli; Otlu, Ali

    2013-09-01

    This study was conducted to evaluate a possible protective role of apricot in apoptotic cell death induced by methotrexate (MTX) and renal damage by different histological and biochemical parameters. Twenty-eight rats were divided into four groups, control, apricot, methotrexate, and apricot + methotrexate. Methotrexate induced renal failure, as shown by significant serum creatinine and urea elevation. Additionally, the results indicated that methotrexate significantly induced lipid peroxidation and reduced antioxidant activities in rats. In contrast, apricot significantly prevented toxic effects of methotrexate via increased catalase, superoxide dismutase, and glutathione levels but decreased formation of malondialdehyde. Also, it was determined that exposure to methotrexate leads to significant histological damage in kidney tissue such as glomerulosclerosis and apoptosis. On the other hand, these effects can be eliminated with apricot diet. These data indicate that apricot may be useful in preventing undesirable effects of MTX such as nephrotoxicity.

  19. DNA damage in hemodialysis patients with chronic kidney disease; a test of the role of diabetes mellitus; a comet assay investigation.

    PubMed

    Mamur, Sevcan; Unal, Fatma; Altok, Kadriye; Deger, Serpil Muge; Yuzbasioglu, Deniz

    2016-04-01

    The incidence of chronic kidney disease (CKD) is increasing rapidly. Diabetes mellitus (DM) is the most important cause of CKD. We studied the possible role of DM in CKD patients with respect to DNA damage, as assessed by the comet assay in 60 CKD patients (with or without DM) undergoing hemodialysis and in 26 controls. Effects of other factors, such as age, sex, hypertension, duration of hemodialysis, body mass index (BMI), and levels of hemoglobin (HB), intact parathormone (iPTH), and ferritin (FER), were also examined. Primary DNA damage measured by the comet assay was significantly higher in CKD patients than in controls. Among CKD patients, the following correlations were observed. (1) There was no difference in comet tail length or tail intensity between diabetic and non-diabetic individuals. (2) Age, sex, hemoglobin, hypertension, duration of hemodialysis, and ferritin levels affected neither tail length nor intensity. (3) BMI values above 25kg/m(2) and iPTH levels above 300pg/ml were associated with significantly greater comet tail length. Our results indicate that primary DNA damage is increased in CKD patients undergoing hemodialysis, compared to controls; however, DM had no additional effect.

  20. The decline in living kidney donation in the United States: random variation or cause for concern?

    PubMed

    Rodrigue, James R; Schold, Jesse D; Mandelbrot, Didier A

    2013-11-15

    The annual number of living kidney donors in the United States peaked at 6647 in 2004. The preceding decade saw a 120% increase in living kidney donation. However, since 2004, living kidney donation has declined in all but 1 year, resulting in a 13% decline in the annual number of living kidney donors from 2004 to 2011. The proportional decline in living kidney donation has been more pronounced among men, blacks, younger adults, siblings, and parents. In this article, we explore several possible explanations for the decline in living kidney donation, including an increase in medical unsuitability, an aging transplant patient population, financial disincentives, public policies, and shifting practice patterns, among others. We conclude that the decline in living donation is not merely reflective of random variation but one that warrants action by the transplant centers, the broader transplant community, and the state and national governments.

  1. Indigofera oblongifolia mitigates lead-acetate-induced kidney damage and apoptosis in a rat model.

    PubMed

    Dkhil, Mohamed A; Al-Khalifa, Mohamed S; Al-Quraishy, Saleh; Zrieq, Rafat; Abdel Moneim, Ahmed Esmat

    2016-01-01

    This study was conducted to appraise the protective effect of Indigofera oblongifolia leaf extract on lead acetate (PbAc)-induced nephrotoxicity in rats. PbAc was intraperitoneally injected at a dose of 20 mg/kg body weight for 5 days, either alone or together with the methanol extract of I. oblongifolia (100 mg/kg). Kidney lead (Pb) concentration; oxidative stress markers including lipid peroxidation, nitrite/nitrate, and glutathione (GSH); and antioxidant enzyme activities, namely superoxide dismutase, catalase, GSH peroxidase, and GSH reductase were all determined. The PbAc injection elicited a marked elevation in Pb concentration, lipid peroxidation, and nitrite/nitrate, with a concomitant depletion in GSH content compared with the control and a remarkable decrease in antioxidant enzymes. Oxidant/antioxidant imbalance, Pb accumulation, and histological changes in the kidneys were successfully prevented by the pre-administration of I. oblongifolia extract. In addition, the elevated expression of proapoptotic protein, Bax, in the kidneys of the PbAc-injected rats was reduced as a result of I. oblongifolia pre-administration, while the hitherto reduced expression of the anti-apoptotic protein Bcl-2 was elevated. Based on the current findings, it can be concluded that I. oblongifolia successfully minimizes the deleterious effects in kidney function and histological coherence associated with nephrotoxicity by strengthening the antioxidant defense system, suppressing oxidative stress, and mitigating apoptosis.

  2. Indigofera oblongifolia mitigates lead-acetate-induced kidney damage and apoptosis in a rat model

    PubMed Central

    Dkhil, Mohamed A; Al-Khalifa, Mohamed S; Al-Quraishy, Saleh; Zrieq, Rafat; Abdel Moneim, Ahmed Esmat

    2016-01-01

    This study was conducted to appraise the protective effect of Indigofera oblongifolia leaf extract on lead acetate (PbAc)-induced nephrotoxicity in rats. PbAc was intraperitoneally injected at a dose of 20 mg/kg body weight for 5 days, either alone or together with the methanol extract of I. oblongifolia (100 mg/kg). Kidney lead (Pb) concentration; oxidative stress markers including lipid peroxidation, nitrite/nitrate, and glutathione (GSH); and antioxidant enzyme activities, namely superoxide dismutase, catalase, GSH peroxidase, and GSH reductase were all determined. The PbAc injection elicited a marked elevation in Pb concentration, lipid peroxidation, and nitrite/nitrate, with a concomitant depletion in GSH content compared with the control and a remarkable decrease in antioxidant enzymes. Oxidant/antioxidant imbalance, Pb accumulation, and histological changes in the kidneys were successfully prevented by the pre-administration of I. oblongifolia extract. In addition, the elevated expression of proapoptotic protein, Bax, in the kidneys of the PbAc-injected rats was reduced as a result of I. oblongifolia pre-administration, while the hitherto reduced expression of the anti-apoptotic protein Bcl-2 was elevated. Based on the current findings, it can be concluded that I. oblongifolia successfully minimizes the deleterious effects in kidney function and histological coherence associated with nephrotoxicity by strengthening the antioxidant defense system, suppressing oxidative stress, and mitigating apoptosis. PMID:27330278

  3. Nickel chloride (NiCl2)-caused inflammatory responses via activation of NF-κB pathway and reduction of anti-inflammatory mediator expression in the kidney

    PubMed Central

    Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Wu, Bangyuan; Chen, Kejie

    2015-01-01

    Nickel (Ni) or Ni compounds target a number of organs and produce multiple toxic effects. Kidney is the major organ for Ni accumulation and excretion. There are no investigations on the Ni- or Ni compounds-induced renal inflammatory responses in human beings and animals at present. Therefore, we determined NiCl2-caused alteration of inflammatory mediators, and functional damage in the broiler's kidney by the methods of biochemistry, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Dietary NiCl2 in excess of 300 mg/kg caused the renal inflammatory responses that characterized by increasing mRNA expression levels of the pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) via the activation of nucleic factor κB (NF-κB), and decreasing mRNA expression levels of the anti-inflammatory mediators including interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-13 (IL-13). Concurrently, NiCl2 caused degeneration, necrosis and apoptosis of the tubular cells, which was consistent with the alteration of renal function parameters including elevated alkaline phosphatase (AKP) activity, and reduced activities of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), calcium adenosine triphosphatase (Ca2+-ATPase), lactic dehydrogenase (LDH), succinate dehydrogenase (SDH) and acid phosphatase (ACP) in the kidney. The above-mentioned results present that the activation of NF-κB pathway and reduction of anti-inflammatory mediator expression are main mechanisms of NiCl2-caused renal inflammatory responses and that the renal function is decreased or impaired after NiCl2-treated. PMID:26417933

  4. Chronic Kidney Disease

    MedlinePlus

    You have two kidneys, each about the size of your fist. Their main job is to filter wastes and excess water out of ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

  5. Chronic Broca's Aphasia Is Caused by Damage to Broca's and Wernicke's Areas

    PubMed Central

    Fridriksson, Julius; Fillmore, Paul; Guo, Dazhou; Rorden, Chris

    2015-01-01

    Despite being perhaps the most studied form of aphasia, the critical lesion location for Broca's aphasia has long been debated, and in chronic patients, cortical damage often extends far beyond Broca's area. In a group of 70 patients, we examined brain damage associated with Broca's aphasia using voxel-wise lesion-symptom mapping (VLSM). We found that damage to the posterior portion of Broca's area, the pars opercularis, is associated with Broca's aphasia. However, several individuals with other aphasic patterns had considerable damage to pars opercularis, suggesting that involvement of this region is not sufficient to cause Broca's aphasia. When examining only individuals with pars opercularis damage, we found that patients with Broca's aphasia had greater damage in the left superior temporal gyrus (STG; roughly Wernicke's area) than those with other aphasia types. Using discriminant function analysis and logistic regression, based on proportional damage to the pars opercularis and Wernicke's area, to predict whether individuals had Broca's or another types of aphasia, over 95% were classified correctly. Our findings suggest that persons with Broca's aphasia have damage to both Broca's and Wernicke's areas, a conclusion that is incongruent with classical neuropsychology, which has rarely considered the effects of damage to both areas. PMID:25016386

  6. Limited damage of tissue mimic caused by a collapsing bubble under low-frequency ultrasound exposure.

    PubMed

    Yoshida, Kenji; Obata, Kazuya; Tsukamoto, Akira; Ushida, Takashi; Watanabe, Yoshiaki

    2014-08-01

    In this study, we investigated the bubble induced serious damage to tissue mimic exposed to 27-kHz ultrasound. The initial bubble radius ranged from 80 to 100 μm, which corresponded approximately to the experimentally-evaluated resonant radius of the given ultrasound frequency. The tissue mimic consisted of 10 wt% gelatine gel covered with cultured canine kidney epithelial cells. The collapsing bubble behaviour during the ultrasound exposure with negative peak pressures of several hundred kPa was captured by a high-speed camera system. After ultrasound exposure, a cell viability test was conducted based on microscopic bright-field images and fluorescence images for living and dead cells. In the viability test, cells played a role in indicating the damaged area. The bubble oscillations killed the cells, and on occasion detached layers of cultured cells from the gel. The damaged area was comparable or slightly larger than the initial bubble size, and smaller than the maximum bubble size. We concluded that only a small area in close proximity to the bubble could be damaged even above transient cavitation threshold.

  7. The Ask-Upmark kidney: a curable cause of hypertension in young patients.

    PubMed

    Babin, J; Sackett, M; Delage, C; Lebel, M

    2005-04-01

    We are reporting a case of arterial hypertension in a young woman who had an atrophic kidney with a cortical groove and histological features of the Ask-Upmark kidney. Her hypertension was renin dependent and the patient was cured following nephrectomy. Controversy on the pathogenesis of this clinical entity is briefly reviewed.

  8. DNA Damage in Euonymus japonicus Leaf Cells Caused by Roadside Pollution in Beijing

    PubMed Central

    Li, Tianxin; Zhang, Minjie; Gu, Ke; Herman, Uwizeyimana; Crittenden, John; Lu, Zhongming

    2016-01-01

    The inhalable particles from vehicle exhaust can cause DNA damage to exposed organisms. Research on DNA damage is primarily focused on the influence of specific pollutants on certain species or the effect of environmental pollution on human beings. To date, little research has quantitatively studied the relationship between roadside pollution and DNA damage. Based on an investigation of the roadside pollution in Beijing, Euonymus japonicus leaves of differing ages grown in heavily-polluted sections were chosen as biomonitors to detect DNA damage using the comet assay technique. The percentage of DNA in the tail and tail moment was chosen as the analysis index based on SPSS data analysis. The roadside samples showed significantly higher levels of DNA damage than non-roadside samples, which increased in older leaves, and the DNA damage to Euonymus japonicus leaf cells was positively correlated with haze-aggravated roadside pollution. The correlation between damage and the Air Quality Index (AQI) are 0.921 (one-year-old leaves), 0.894 (two-year-old leaves), and 0.878 (three-year-old leaves). Over time, the connection between DNA damage and AQI weakened, with the sensitivity coefficient for δyear 1 being larger than δyear 2 and δyear 3. These findings support the suitability and sensitivity of the comet assay for surveying plants for an estimation of DNA damage induced by environmental genotoxic agents. This study might be applied as a preliminary quantitative method for Chinese urban air pollution damage assessment caused by environmental stress. PMID:27455298

  9. [MALT B cell lymphoma with kidney damage and monoclonal gammopathy: a case study and literature review].

    PubMed

    Peces, R; Vega-Cabrera, C; Peces, C; Pobes, A; Fresno, M F

    2010-01-01

    We report a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) involving the left kidney and simultaneous onset of a monoclonal gammopathy IgM kappa. No predisposing local inflammatory condition was identified. Following left nephrectomy, the renal specimen showed the centrocyte like cells and lymphoid cells in the lymphoepithelial lesions were positive for CD20 and CD79α. The neoplastic cells expressed monotypic cytoplasmic IgM kappa. The demonstration of bone marrow cells of B-lineage expressing the same monoclonal protein as the tumor suggested bone marrow involvement, even in the absence of identical morphology. Despite chemotherapy and rituximab treatment, clinical follow-up showed right kidney extension with high-grade transformation, and finally systemic dissemination. This case illustrates that the kidney is among the sites that may be involved by MALT B-cell lymphomas in a primary or secondary fashion, and the need for expanded investigation of the possible dissemination. We review the literature on this unusual extranodal lymphoma.

  10. Hypogonadism in males with chronic kidney disease: another cause of resistance to erythropoiesis-stimulating agents?

    PubMed

    Stenvinkel, Peter; Bárány, Peter

    2012-01-01

    Anemia, inflammation, resistance to erythropoiesis-stimulating agents (ESA) and hypogonadism (testosterone deficiency) are highly prevalent conditions, which heralds poor prognosis, in chronic kidney disease (CKD). It has been speculated that testosterone stimulates erythropoiesis via production of hematopoietic growth factors and possibly improvement of iron bioavailability. Where as inflammation stimulates synthesis of the liver-derived iron regulatory protein hepcidin, a recent study suggests that testosterone inhibits hepcidin synthesis, thus offering a possible novel mechanism for testosterone-induced erythropoiesis. As any agent that lowers hepcidin may be an effective strategy to normalize iron homeostasis and overcome renal anemia, testosterone deficiency should be considered in this patient group. Indeed, a recent study in males with CKD showed that hypogonadism may be an additional cause of anemia and reduced ESA responsiveness. Thus, a randomized controlled trial is needed to test the possibility that restoration of testosterone levels in hypogonadal CKD males may translate into lower prevalence of anemia, better ESA responsiveness and better quality of life.

  11. Multiple liver cyst infection caused by Salmonella ajiobo in autosomal dominant polycystic kidney disease.

    PubMed

    Himeno, Akihiro; Suzuki, Hiromichi; Suzuki, Yumiko; Kawaguchi, Hiroshi; Isozaki, Taisuke

    2013-06-01

    Most Salmonella infections are usually self-limited; however, some cases of enteritis result in bacteremia, and there have been reports of extra-intestinal manifestations. Cyst infections are rare, and few cases have been reported. We report a 77-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) complicated with a multiple liver cyst infection caused by Salmonella ajiobo. The patient was hospitalized for fever, abdominal pain, and diarrhea. The blood culture identified Salmonella sp., but the source of infection was not detected by computed tomography or echography. The patient was initially treated with meropenem followed by fluoroquinolones for 3 weeks; however, her C-reactive protein level was high (10-20 mg/dL) even after the antimicrobial therapy. The patient had a fever again on day 51, and Salmonella sp. was detected again from 2 sets of blood cultures. Despite the antimicrobial treatment, her general condition gradually deteriorated, and she died on day 66. The autopsy revealed that most of the liver had been replaced by cysts. Several cysts filled with pus were detected and Salmonella ajiobo was identified in the pus of the infected cysts.

  12. Acute Kidney Failure

    MedlinePlus

    ... through your urine Impaired blood flow to the kidneys Diseases and conditions that may slow blood flow ... anaphylaxis) Severe burns Severe dehydration Damage to the kidneys These diseases, conditions and agents may damage the ...

  13. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence.

    PubMed

    Sellarés, J; de Freitas, D G; Mengel, M; Reeve, J; Einecke, G; Sis, B; Hidalgo, L G; Famulski, K; Matas, A; Halloran, P F

    2012-02-01

    We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming to assign a cause to every failure. We followed 315 allograft recipients who underwent indication biopsies at 6 days to 32 years posttransplant. Sixty kidneys progressed to failure in the follow-up period (median 31.4 months). Failure was rare after T-cell-mediated rejection and acute kidney injury and common after antibody-mediated rejection or glomerulonephritis. We developed rules for using biopsy diagnoses, HLA antibody and clinical data to explain each failure. Excluding four with missing information, 56 failures were attributed to four causes: rejection 36 (64%), glomerulonephritis 10 (18%), polyoma virus nephropathy 4 (7%) and intercurrent events 6 (11%). Every rejection loss had evidence of antibody-mediated rejection by the time of failure. Among rejection losses, 17 of 36 (47%) had been independently identified as nonadherent by attending clinicians. Nonadherence was more frequent in patients who progressed to failure (32%) versus those who survived (3%). Pure T-cell-mediated rejection, acute kidney injury, drug toxicity and unexplained progressive fibrosis were not causes of loss. This prospective cohort indicates that many actual failures after indication biopsies manifest phenotypic features of antibody-mediated or mixed rejection and also underscores the major role of nonadherence.

  14. Ricin crosses polarized human intestinal cells and intestines of ricin-gavaged mice without evident damage and then disseminates to mouse kidneys.

    PubMed

    Flora, Alyssa D; Teel, Louise D; Smith, Mark A; Sinclair, James F; Melton-Celsa, Angela R; O'Brien, Alison D

    2013-01-01

    Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin on the gastrointestinal tract and organs of mice after dissemination of toxin from the gut. We first showed that ricin adhered in a specific pattern to human small bowel intestinal sections, the site within the mouse gut in which a variable degree of damage has been reported by others. We then monitored the movement of ricin across polarized human HCT-8 intestinal monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed that, in both systems, ricin trafficked through the cells without apparent damage until 24 hours post intoxication. We delivered a lethal dose of purified fluorescently-labeled ricin to mice by oral gavage and followed transit of the toxin from the gastrointestinal tracts to the internal organs by in vivo imaging of whole animals over time and ex vivo imaging of organs at various time points. In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed them for the presence of ricin and for histological damage. Finally, we compared serum chemistry values from buffer-treated versus ricin-intoxicated animals. We conclude that ricin transverses human intestinal cells and mouse intestinal cells in situ prior to any indication of enterocyte damage and that ricin rapidly reaches the kidneys of intoxicated mice. We also propose that mice intoxicated orally with ricin likely die from distributive shock.

  15. Association of TSH Elevation with All-Cause Mortality in Elderly Patients with Chronic Kidney Disease

    PubMed Central

    Chuang, Mei-hsing; Liao, Kuo-Meng; Hung, Yao-Min; Chou, Yi-Chang; Chou, Pesus

    2017-01-01

    Chronic kidney disease (CKD) is a widespread condition in the global population and is more common in the elderly. Thyroid-stimulating hormone (TSH) level increases with aging, and hypothyroidism is highly prevalent in CKD patients. However, the relationship between low thyroid function and mortality in CKD patients is unclear. Therefore, we conducted a retrospective cohort study to examine the relationship between TSH elevation and all-cause mortality in elderly patients with CKD. This retrospective cohort study included individuals ≥65 years old with CKD (n = 23,786) in Taipei City. Health examination data from 2005 to 2010 were provided by the Taipei Databank for Public Health Analysis. Subjects were categorized according to thyroid-stimulating hormone (TSH) level as follows: low normal (0.34cause mortality was increased in the elevated I group (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.02–1.45) and elevated II group (HR, 1.30; 95% CI, 1.00–1.69). We found a significant association between TSH elevation and all-cause mortality in this cohort of elderly persons with CKD. However, determining the benefit of treatment for moderately elevated TSH level (5.2–10 mIU/L) in elderly patients with CKD will require a

  16. Association of TSH Elevation with All-Cause Mortality in Elderly Patients with Chronic Kidney Disease.

    PubMed

    Chuang, Mei-Hsing; Liao, Kuo-Meng; Hung, Yao-Min; Chou, Yi-Chang; Chou, Pesus

    2017-01-01

    Chronic kidney disease (CKD) is a widespread condition in the global population and is more common in the elderly. Thyroid-stimulating hormone (TSH) level increases with aging, and hypothyroidism is highly prevalent in CKD patients. However, the relationship between low thyroid function and mortality in CKD patients is unclear. Therefore, we conducted a retrospective cohort study to examine the relationship between TSH elevation and all-cause mortality in elderly patients with CKD. This retrospective cohort study included individuals ≥65 years old with CKD (n = 23,786) in Taipei City. Health examination data from 2005 to 2010 were provided by the Taipei Databank for Public Health Analysis. Subjects were categorized according to thyroid-stimulating hormone (TSH) level as follows: low normal (0.34cause mortality was increased in the elevated I group (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.02-1.45) and elevated II group (HR, 1.30; 95% CI, 1.00-1.69). We found a significant association between TSH elevation and all-cause mortality in this cohort of elderly persons with CKD. However, determining the benefit of treatment for moderately elevated TSH level (5.2-10 mIU/L) in elderly patients with CKD will require a well

  17. 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.

  18. Hydrogen sulfide ameliorates the kidney dysfunction and damage in cisplatin-induced nephrotoxicity in rat

    PubMed Central

    Ahangarpour, Akram; Abdollahzade Fard, Amin; Gharibnaseri, Mohammad Kazem; Jalali, Taha; Rashidi, Iran

    2014-01-01

    Hydrogen Sulfide (H2S) prevents and treats a variety of disorders via its cytoprotective effects. However, the effects of H2S on rats with cisplatin (CP) nephrotoxicity are unclear. The aim was to study the effects of H2S on rats with CP nephrotoxicity. Thirty male Sprague-Dawley rats were divided into three groups: control group, nephrotoxic group received single dose of CP (6 mg kg-1) and nephrotoxic groups that received single dose 100 µmol kg-1 NaHS. On fifth day after injection, urine of each rat was collected over a 24-hr period. Animals were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and kidneys were obtained, prepared for light microscopy evaluation, lipid peroxidation content and laboratory analysis. The results showed that plasma urea (226%), creatinine (271%), renal lipid peroxidation content (151%), Na and K fractional excretion, urine protein, volume and kidney weight in CP nephrotoxic rats were significantly higher and urine osmolarity and creatinine clearance lower than in controls. Increases of the proximal tubular cells apoptosis and mesangial matrix in CP nephrotoxicity group rats were observed. Hydrogen sulfide reversed the CP-induced changes in the experimental rats H2S prevented the progression of CP nephrotoxicity in rats possibly through its cytoprotective effects such as antioxidant properties. PMID:25568705

  19. Effects of atrazine on the oxidative damage of kidney in Wister rats

    PubMed Central

    Liu, Wei; Du, Yanwei; Liu, Jian; Wang, Hebin; Sun, Daguang; Liang, Dongmei; Zhao, Lijing; Shang, Jincheng

    2014-01-01

    The environmental persistence and bioaccumulation of herbicide atrazine may pose a significant threat to human health. In this experiment, 4 weeks old female Wister rats were treated by 0, 5, 25 and 125 mg/kg atrazine respectively for 28 days, and the oxidative stress responses as well as the activations of Nrf2 signaling pathway in kidney tissues induced by atrazine were observed. The results showed that after be treated by atrazine, the Blood urea nitrogen (BUN) and creatinine (CREA) levels in serum were increased, the contents of nitric oxide (NO) and malondialdehyde (MDA) in the kidney tissue homogenates were increased, the over-expressed Nrf2 transferred into the nuclei and played an antioxidant role by up-regulated the expression of II phase detoxifying enzymes such as heme oxygenase-1 (HO1) and NAD(P)H quinone oxidoreductase (NQO1) and the expression of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). PMID:25419354

  20. Measurements and analysis of surface damage on oil-impregnated insulation paper caused by partial discharge

    NASA Astrophysics Data System (ADS)

    Yan, Jiaming; Liao, Ruijin; Yang, Lijun; Zhu, Mengzhao

    2011-05-01

    Surface topography, surface roughness, and surface conductivity of oil-impregnated insulation paper were studied during the damage process caused by partial discharge within the cavity of the paper. Products generated on the surface during this process were studied, as well. According to phase-resolved partial discharge patterns, the damage process can be divided into five stages. At each of the stages, surface conditions of insulation were analyzed by optical microscopy, scanning electron microscopy, atomic force microscopy and high-resistance meter. 'Ablating', 'peeling', 'cracking in silk', 'pitting' and 'electrical treeing' appear on insulation surfaces one after another during the five stages of the damage process, along with sequential generation of droplets and crystalline solids. Surface roughness initially decreases, then increases. Finally, surface conductivity exhibits a general increasing trend, before it eventually stabilizes. However, its growth rate varies in different stages of damage.

  1. 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.

  2. Subcutis calcinosis caused by injection of calcium-containing heparin in a chronic kidney injury patient.

    PubMed

    Fatma, Lilia Ben; El Ati, Zohra; Azzouz, Haifa; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hédi Ben; Béji, Soumaya; Zouaghi, Karim; Zitouna, Moncef; Moussa, Fatma Ben

    2014-09-01

    Subcutis calcinosis, characterized by abnormal calcium deposits in the skin, is a rare complication of using calcium-containing heparin occurring in patients with advanced renal failure. We report the case of an 83-year-old female, a known case of chronic kidney disease (CKD) for four years with recent worsening of renal failure requiring hospitalization and hemodialysis. She developed subcutis calcinosis following injection of calcium-containing heparin. Biochemical tests showed serum parathormone level at 400 pg/dL, hypercalcemia, elevated calcium-phosphate product and monoclonal gammopathy related to multiple myeloma. She developed firm subcutaneous nodules in the abdomen and the thighs, the injection sites of Calciparin ® (calcium nadroparin) that was given as a preventive measure against deep vein thrombosis. The diagnosis of subcutis calcinosis was confirmed by the histological examination showing calcium deposit in the dermis and hypodermis. These lesions completely disappeared after discontinuing calcium nadroparin injections. Subcutis calcinosis caused by injections of calcium-containing heparin is rare, and, to the best our knowledge, not more than 12 cases have been reported in the literature. Pathogenesis is not well established but is attributed to the calcium disorders usually seen in advanced renal failure. Diagnosis is confirmed by histological tests. Outcome is mostly favorable. The main differential diagnosis is calciphylaxis, which has a poor prognosis. Even though rarely reported, we should be aware that CKD patients with elevated calcium-phosphorus product can develop subcutis calcinosis induced by calcium-containing heparin. When it occurs, fortunately and unlike calciphylaxis, outcome is favorable.

  3. Foliar Nutritional Quality Explains Patchy Browsing Damage Caused by an Invasive Mammal

    PubMed Central

    Windley, Hannah R.; Barron, Mandy C.; Holland, E. Penelope; Starrs, Danswell; Ruscoe, Wendy A.; Foley, William J.

    2016-01-01

    Introduced herbivores frequently inflict significant, yet patchy damage on native ecosystems through selective browsing. However, there are few instances where the underlying cause of this patchy damage has been revealed. We aimed to determine if the nutritional quality of foliage could predict the browsing preferences of an invasive mammalian herbivore, the common brushtail possum (Trichosurus vulpecula), in a temperate forest in New Zealand. We quantified the spatial and temporal variation in four key aspects of the foliar chemistry (total nitrogen, available nitrogen, in vitro dry matter digestibility and tannin effect) of 275 trees representing five native tree species. Simultaneously, we assessed the severity of browsing damage caused by possums on those trees in order to relate selective browsing to foliar nutritional quality. We found significant spatial and temporal variation in nutritional quality among individuals of each tree species examined, as well as among tree species. There was a positive relationship between the available nitrogen concentration of foliage (a measure of in vitro digestible protein) and the severity of damage caused by browsing by possums. This study highlights the importance of nutritional quality, specifically, the foliar available nitrogen concentration of individual trees, in predicting the impact of an invasive mammal. Revealing the underlying cause of patchy browsing by an invasive mammal provides new insights for conservation of native forests and targeted control of invasive herbivores in forest ecosystems. PMID:27171381

  4. 76 FR 44985 - Pipeline Safety: Potential for Damage to Pipeline Facilities Caused by Flooding

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-27

    ...] [FR Doc No: 2011-19029] DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket No. PHMSA-2011-0177] Pipeline Safety: Potential for Damage to Pipeline Facilities Caused by Flooding AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT....

  5. Crop damage caused by Powdery Mildew on Hop and its relationship to late season management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Powdery mildew of hop (Podosphaera macularis) may cause economic loss due to reductions in cone yield and quality. Quantitative estimates of crop damage from powdery mildew remain poorly characterised, especially the effect of late season disease management on crop yield and quality. Field studies i...

  6. Chelation in metal intoxication. XIV. Comparative effect of thiol and amino chelators on lead-poisoned rats with normal or damaged kidneys

    SciTech Connect

    Tandon, S.K.; Flora, S.J.; Singh, S.

    1985-06-30

    D-Penicillamine (DPA), diethyldithiocarbamate (DDC), L-cysteine, ethylenediaminetetraacetic acid (EDTA), cyclohexylenediaminetetraacetic acid (CDTA), and diethylene triamine pentaacetic acid (DTPA) were compared for their efficacy to enhance urinary excretion of Pb, to reduce Pb concentration of body organs, and to restore the enhanced urinary excretion of delta-aminolevulinic acid (delta-ALA), the inhibited activities of blood delta-ALA dehydratase, and renal enzymes in Pb-administered rats (10 mg/kg, po, 4 weeks) with normal or experimentally damaged kidneys. The acute renal damage was induced by uranyl acetate (3 mg/kg, sc, once) prior to treatment with the chelators (0.3 mmol/kg, ip, twice) and evaluated by enhanced urinary excretion of diagnostic enzymes and inhibition in their renal activities. Among thiol chelators, DPA was the most effective followed by DDC in enhancing the urinary excretion of Pb, reducing the concentration of Pb in blood, kidneys and liver, and in restoring Pb-induced biological alterations in urine, blood, and kidneys. Among amino carboxylic acids, DTPA was the most effective and EDTA and CDTA were about equally potent in countering Pb toxicity. Protection was more marked in animals with normal kidneys than in those with acutely damaged kidneys.

  7. Untethering an unusual cause of kidney injury in a teenager with Down syndrome.

    PubMed

    Yen, Elizabeth; Miele, Niel F; Barone, Joseph G; Tyagi, Rachana; Weiss, Lynne S

    2014-11-01

    Acute kidney injury (AKI) is characterized by the acute nature and the inability of kidneys to maintain fluid homeostasis as well as adequate electrolyte and acid-base balance, resulting in an accumulation of nitrogenous waste and elevation of serum blood urea nitrogen and creatinine values. Acute kidney injury may be a single isolated event, yet oftentimes, it results from an acute chronic kidney disease. It is critical to seek out the etiology of AKI and to promptly manage the underlying chronic kidney disease to prevent comorbidities and mortality that may ensue. We described a case of a 16-year-old adolescent girl with Down syndrome who presented with AKI and electrolyte aberrance.Abdominal and renal ultrasounds demonstrated a significantly dilated bladder as well as frank hydronephrosis and hydroureter bilaterally. Foley catheter was successful in relieving the obstruction and improving her renal function. However, a magnetic resonance imaging was pursued in light of her chronic constipation and back pain, and it revealed a structural defect (tethered cord) that underlies a chronic process that was highly likely contributory to her AKI. She was managed accordingly with a guarded result and required long-term and close monitoring.

  8. Air purifiers that diffuse reactive oxygen species potentially cause DNA damage in the lung.

    PubMed

    Kawamoto, Kosuke; Sato, Itaru; Yoshida, Midori; Tsuda, Shuji

    2010-12-01

    Several appliance manufacturers have recently released new type air purifiers that can disinfect bacteria, fungi and viruses by diffusing reactive oxygen species (ROS) into the air. In this study, mice were exposed to the outlet air from each of 3 air purifiers from different manufacturers (A, B, C), and the lung was examined for DNA damage, lipid peroxidation and histopathology to confirm the safety of these air purifiers. Neither abnormal behavior during exposure nor gross abnormality at necropsy was observed. No histopathological changes were also observed in the lung. However, significant increase of DNA damage was detected by the comet assay in the lung immediately after the direct exposure for 48 hr to models A and B, and for 16 hr to model B. As for model B, DNA migration was also increased by 2 hr exposure in a 1 m(3) plastic chamber but not by 48 hr exposure in a room (12.6 m(3)). Model C did not cause DNA damage. Lipid peroxidation and 8-hydroxy deoxyguanosine (8-OH-dG) was not increased under the conditions DNA damage was detected by the comet assay. The present results revealed that some models of air purifiers that diffuse ROS potentially cause DNA damage in the lung although the mechanism was left unsolved.

  9. Analyses of the secondary particle radiation and the DNA damage it causes to human keratinocytes

    SciTech Connect

    Lebel E.; Rusek A.; Sivertz, M.; Yip, K.; Thompson, K.; Tafrov, S.

    2011-11-22

    High-energy protons, and high mass and energy ions, along with the secondary particles they produce, are the main contributors to the radiation hazard during space explorations. Skin, particularly the epidermis, consisting mainly of keratinocytes with potential for proliferation and malignant transformation, absorbs the majority of the radiation dose. Therefore, we used normal human keratinocytes to investigate and quantify the DNA damage caused by secondary radiation. Its manifestation depends on the presence of retinol in the serum-free media, and is regulated by phosphatidylinositol 3-kinases. We simulated the generation of secondary radiation after the impact of protons and iron ions on an aluminum shield. We also measured the intensity and the type of the resulting secondary particles at two sample locations; our findings agreed well with our predictions. We showed that secondary particles inflict DNA damage to different extents, depending on the type of primary radiation. Low-energy protons produce fewer secondary particles and cause less DNA damage than do high-energy protons. However, both generate fewer secondary particles and inflict less DNA damage than do high mass and energy ions. The majority of cells repaired the initial damage, as denoted by the presence of 53BPI foci, within the first 24 hours after exposure, but some cells maintained the 53BP1 foci longer.

  10. Analyses of the Secondary Particle Radiation and the DNA Damage it Causes to Human Keratinocytes

    SciTech Connect

    Lebel E. A.; Tafrov S.; Rusek, A.; Sivertz, M. B.; Yip, K.; Thompson, K. H.

    2011-11-01

    High-energy protons, and high mass and energy ions, along with the secondary particles they produce, are the main contributors to the radiation hazard during space explorations. Skin, particularly the epidermis, consisting mainly of keratinocytes with potential for proliferation and malignant transformation, absorbs the majority of the radiation dose. Therefore, we used normal human keratinocytes to investigate and quantify the DNA damage caused by secondary radiation. Its manifestation depends on the presence of retinol in the serum-free media, and is regulated by phosphatidylinositol 3-kinases. We simulated the generation of secondary radiation after the impact of protons and iron ions on an aluminum shield. We also measured the intensity and the type of the resulting secondary particles at two sample locations; our findings agreed well with our predictions. We showed that secondary particles inflict DNA damage to different extents, depending on the type of primary radiation. Low-energy protons produce fewer secondary particles and cause less DNA damage than do high-energy protons. However, both generate fewer secondary particles and inflict less DNA damage than do high mass and energy ions. The majority of cells repaired the initial damage, as denoted by the presence of 53BPI foci, within the first 24 hours after exposure, but some cells maintained the 53BP1 foci longer.

  11. Management of wildlife causing damage at Argonne National Laboratory-East, DuPage County, Illinois

    SciTech Connect

    1995-04-01

    The DOE, after an independent review, has adopted an Environmental Assessment (EA) prepared by the US Department of Agriculture (USDA) which evaluates use of an Integrated Wildlife Damage Management approach at Argonne National Laboratory-East (ANL-E) in DuPage County, Illinois (April 1995). In 1994, the USDA issued a programmatic Environmental Impact Statement (EIS) that covers nationwide animal damage control activities. The EA for Management of Wildlife Causing Damage at ANL-E tiers off this programmatic EIS. The USDA wrote the EA as a result of DOE`s request to USDA to prepare and implement a comprehensive Wildlife Management Damage Plan; the USDA has authority for animal damage control under the Animal Damage Control Act of 1931, as amended, and the Rural Development, Agriculture and Related Agencies Appropriations Act of 1988. DOE has determined, based on the analysis in the EA, that the proposed action does not constitute a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act of 1969 (NEPA). Therefore, the preparation of an EIS is not required. This report contains the Environmental Assessment, as well as the Finding of No Significant Impact (FONSI).

  12. Example Building Damage Caused by Mining Exploitation in Disturbed Rock Mass

    NASA Astrophysics Data System (ADS)

    Florkowska, Lucyna

    2013-06-01

    Issues concerning protection of buildings against the impact of underground coal mining pose significant scientific and engineering challenges. In Poland, where mining is a potent and prominent industry assuring domestic energy security, regions within reach of mining influences are plenty. Moreover, due to their industrial character they are also densely built-up areas. Because minerals have been extracted on an industrial scale in majority of those areas for many years, the rock mass structure has been significantly disturbed. Hence, exploitation of successive layers of multi-seam deposits might cause considerable damage - both in terms of surface and existing infrastructure networks. In the light of those facts, the means of mining and building prevention have to be improved on a regular basis. Moreover, they have to be underpinned by reliable analyses holistically capturing the comprehensive picture of the mining, geotechnical and constructional situation of structures. Scientific research conducted based on observations and measurements of mining-induced strain in buildings is deployed to do just that. Presented in this paper examples of damage sustained by buildings armed with protection against mining influences give an account of impact the mining exploitation in disturbed rock mass can have. This paper is based on analyses of mining damage to church and Nursing Home owned by Evangelical Augsburg Parish in Bytom-Miechowice. Neighbouring buildings differ in the date they were built, construction, building technology, geometry of the building body and fitted protection against mining damage. Both the buildings, however, have sustained lately significant deformation and damage caused by repeated mining exploitation. Selected damage has been discussed hereunder. The structures have been characterised, their current situation and mining history have been outlined, which have taken their toll on character and magnitude of damage. Description has been supplemented

  13. Escalating chronic kidney diseases of multi-factorial origin in Sri Lanka: causes, solutions, and recommendations.

    PubMed

    Wimalawansa, Sunil J

    2014-11-01

    During the last two decades, Sri Lanka, located close to the equator, has experienced an escalating incidence of chronic kidney disease (CKD) of unknown aetiology (CKDue) in dry zonal areas. Similar incidences of unusual CKDs have been reported in the dry zonal, agricultural areas of several other equatorial countries. In Sri Lanka, the incidence of CKDue is highest in the North Central Province (NCP), where approximately 45 % of the country's paddy fields are located. However, in recent years, the disease has spread into areas adjacent to as well as distant from the NCP. The cause of CKD in Sri Lanka is unknown, and may likely due to interactions of different potential agents; thus, CKD is of multi-factorial origin (CKD-mfo). These factors include, the negative effects from overuse of agrochemicals. Nevertheless, the potential interactions and synergism between probable agents have not been studied. This systematic review discusses the proposed hypotheses and causes of CKD-mfo in Sri Lanka, and ways to decrease the incidence of this disease and to eradicate it, and provide some recommendations. During the past decade, a number of groups have investigated this disorder using different methodologies and reported various correlations, but failed to find a cause. Research has focussed on the contamination of water with heavy metals, agrochemicals, hard water, algae, ionicity, climate change, and so forth. Nevertheless, the levels of any of the pollutants or conditions reported in water in NPC are inconsistent not correlated with the prevalence of the disease, and are too low to be the sole cause of CKD-mfo. Meanwhile, several nephrotoxins prevalent in the region, including medications, leptospirosis, toxic herbs, illicit alcohol, locally grown tobacco, and petrochemicals, as well as the effects of changed habits occured over the past four decades have not been studied to date. Taken together, the geographical distribution and overall findings indicate that

  14. Systemic Autoimmunity in TAM Triple Knockout Mice Causes Inflammatory Brain Damage and Cell Death

    PubMed Central

    Li, Qiutang; Lu, Qingjun; Lu, Huayi; Tian, Shifu; Lu, Qingxian

    2013-01-01

    The Tyro3, Axl and Mertk (TAM) triply knockout (TKO) mice exhibit systemic autoimmune diseases, with characteristics of increased proinflammatory cytokine production, autoantibody deposition and autoreactive lymphocyte infiltration into a variety of tissues. Here we show that TKO mice produce high level of serum TNF-α and specific autoantibodies deposited onto brain blood vessels. The brain-blood barrier (BBB) in mutant brains exhibited increased permeability for Evans blue and fluorescent-dextran, suggesting a breakdown of the BBB in the mutant brains. Impaired BBB integrity facilitated autoreactive T cells infiltrating into all regions of the mutant brains. Brain autoimmune disorder caused accumulation of the ubiquitin-reactive aggregates in the mutant hippocampus, and early formation of autofluorescent lipofuscins in the neurons throughout the entire brains. Chronic neuroinflammation caused damage of the hippocampal mossy fibers and neuronal apoptotic death. This study shows that chronic systemic inflammation and autoimmune disorders in the TKO mice cause neuronal damage and death. PMID:23840307

  15. Combusted but not smokeless tobacco products cause DNA damage in oral cavity cells.

    PubMed

    Gao, Hong; Prasad, G L; Zacharias, Wolfgang

    2014-05-01

    The aim of this work was to investigate genomic DNA damage in human oral cavity cells after exposure to different tobacco product preparations (TPPs). The oral carcinoma cell line 101A, gingival epithelial cells HGEC, and gingival fibroblasts HGF were exposed to TPM (total particulate matter from 3R4F cigarettes), ST/CAS (2S3 smokeless tobacco extract in complete artificial saliva), and NIC (nicotine). Treatments were for 24 h using TPM at its EC-50 doses, ST/CAS and NIC at doses with equi-nicotine units, and high doses for ST/CAS and NIC. Comet assays showed that TPM, but not ST/CAS or NIC, caused substantial DNA breaks in cells; only the high ST/CAS dose caused weak DNA damage. These results were confirmed by immunofluorescence for γ-H2AX protein. These data revealed that the combusted TPP caused substantial DNA damage in all cell types, whereas the two non-combusted TPPs exerted no or only minimal DNA damage. They support epidemiologic evidence on the relative risk associated with consumption of non-combusted versus combusted tobacco products, and help to understand potential genotoxic effects of such products on oral cavity cells.

  16. Pulmonary Phaeohyphomycosis Caused by Phaeoacremonium in a Kidney Transplant Recipient: Successful Treatment with Posaconazole

    PubMed Central

    Monaganti, Saivaralaxmi; Santos, Carlos A. Q.; Markwardt, Andrea; Pence, Morgan A.; Brennan, Daniel C.

    2014-01-01

    We report a rare case of pulmonary phaeohyphomycosis in a 49-year-old woman 6 years after kidney transplantation. She presented with dyspnea, cough, and fatigue. Her chest CT scan revealed nodular opacities in the right upper lung. A fine needle aspirate biopsy culture yielded Phaeoacremonium and surgical pathology of the biopsy showed chronic inflammation. We successfully treated her with posaconazole and managed drug interactions between posaconazole and tacrolimus. This is the second reported case of biopsy-proven pulmonary infection by Phaeoacremonium in a kidney transplant recipient and successfully treated with posaconazole. PMID:24959182

  17. Meta-analysis of attitudes toward damage-causing mammalian wildlife.

    PubMed

    Kansky, Ruth; Kidd, Martin; Knight, Andrew T

    2014-08-01

    Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments.

  18. Possible involvement of microRNAs in vascular damage in experimental chronic kidney disease.

    PubMed

    Taïbi, Fatiha; Metzinger-Le Meuth, Valérie; M'Baya-Moutoula, Eléonore; Djelouat, Mohamed seif el Islam; Louvet, Loïc; Bugnicourt, Jean-Marc; Poirot, Sabrina; Bengrine, Abderrahmane; Chillon, Jean-Marc; Massy, Ziad A; Metzinger, Laurent

    2014-01-01

    Chronic kidney disease (CKD) is associated with vascular calcifications and atherosclerosis. There is a need for novel predictors to allow earlier diagnosis of these disorders, predict disease progression, and improve assessment of treatment response. We focused on microRNAs since they are implicated in a variety of cellular functions in cardiovascular pathology. We examined changes of microRNA expression in aortas of CKD and non-CKD wild type mice and apolipoprotein E knock-out mice, respectively. Both vascular smooth muscle-specific miR-143 and miR-145 expressions were decreased in states of atherosclerosis and/or CKD or both, and the expression level of protein target Myocardin was increased. The inflammatory miR-223 was increased in more advanced stages of CKD, and specific protein targets NFI-A and GLUT-4 were dramatically decreased. Expression of miR-126 was markedly increased and expression of protein targets VCAM-1 and SDF-1 was altered during the course of CKD. The drug sevelamer, commonly used in CKD, corrected partially these changes in microRNA expression, suggesting a direct link between the observed microRNA alterations and uremic vascular toxicity. Finally, miR-126, -143 and -223 expression levels were deregulated in murine serum during the course of experimental CKD. In conclusion, these miRNAs could have role(s) in CKD vascular remodeling and may therefore represent useful targets to prevent or treat complications of CKD.

  19. Proximal fiber tip damage during Holmium:YAG and thulium fiber laser ablation of kidney stones

    NASA Astrophysics Data System (ADS)

    Wilson, Christopher R.; Hardy, Luke A.; Irby, Pierce B.; Fried, Nathaniel M.

    2016-02-01

    The Thulium fiber laser (TFL) is being studied as an alternative to Holmium:YAG laser for lithotripsy. TFL beam originates within an 18-μm-core thulium doped silica fiber, and its near single mode, Gaussian beam profile enables transmission of higher laser power through smaller fibers than possible during Holmium laser lithotripsy. This study examines whether TFL beam profile also reduces proximal fiber tip damage compared to Holmium laser multimodal beam. TFL beam at wavelength of 1908 nm was coupled into 105-μm-core silica fibers, with 35-mJ energy, 500-μs pulse duration, and pulse rates of 50-500 Hz. For each pulse rate, 500,000 pulses were delivered. Magnified images of proximal fiber surfaces were taken before and after each trial. For comparison, 20 single-use, 270-μm-core fibers were collected after clinical Holmium laser lithotripsy procedures using standard settings (600 mJ, 350 μs, 6 Hz). Total laser energy, number of laser pulses, and laser irradiation time were recorded, and fibers were rated for damage. For TFL studies, output power was stable, and no proximal fiber damage was observed after delivery of 500,000 pulses at settings up to 35 mJ, 500 Hz, and 17.5 W average power. In contrast, confocal microscopy images of fiber tips after Holmium lithotripsy showed proximal fiber tip degradation in all 20 fibers. The proximal fiber tip of a 105-μm-core fiber transmitted 17.5 W of TFL power without degradation, compared to degradation of 270-μm-core fibers after transmission of 3.6 W of Holmium laser power. The smaller and more uniform TFL beam profile may improve fiber lifetime, and potentially reduce costs for the surgical disposables as well.

  20. Testicular necrosis and DNA damage caused by deuterated and methylated analogs of 1,2-dibromo-3-chloropropane in the rat

    SciTech Connect

    Soderlund, E.J.; Brunborg, G.; Omichinski, J.G.; Holme, J.A.; Dahl, J.E.; Nelson, S.D.; Dybing, E.

    1988-07-01

    To study the role of metabolism in 1,2-dibromo-3-chloropropane (DBCP)-induced testicular damage in rats, selectively deuterated and methylated analogs of DBCP were given as a single ip dose of 340 mumol/kg and testicular toxicity was determined 10 days after treatment. None of the four deuterated analogs C1-D2-, C2-D1-, C3-D2-, or C1-C2-C3-D5-DBCP reduced the degree of testicular damage compared to DBCP, indicating that metabolic cleavage of a C-H bond was not rate-limiting in DBCP-induced testicular toxicity. Of the five methylated analogs, C1-methyl-, C1-dimethyl-, C2-methyl-, and C3-methyl-DBCP and 1,2-dibromo-4-chlorobutane, only C3-methyl-DBCP caused testicular toxicity. DBCP treatment resulted in increased testicular DNA damage at doses of 85-170 mumol/kg as measured by alkaline elution of DNA from testicular cells isolated 3 hr after in vivo treatment. The perdeutero-DBCP analog induced testicular DNA damage that was at least as extensive as that induced by DBCP. Of the methylated analogs tested, only C3-methyl-DBCP gave a marked dose-dependent increase in testicular DNA damage between 170 and 540 mumol/kg. There were no significant differences in the testicular tissue distribution between DBCP, perdeutero-DBCP, and the methylated DBCP analogs. Furthermore, in distribution studies with DBCP, C1-methyl- and C3-methyl-DBCP, and 1,2-dibromo-4-chlorobutane, the highest tissue concentrations were found in the kidneys, followed by the liver and then the testes. The fact that testicular DNA damage of DBCP and its deuterated and methylated analogs paralleled their ability to cause testicular necrosis and atrophy makes measurement of DNA damage a very useful correlate in mechanistic studies of DBCP-induced testicular cell death.

  1. Fatal Granulomatous Amoebic Encephalitis Caused by Acanthamoeba in a Patient With Kidney Transplant: A Case Report

    PubMed Central

    Salameh, Ahmad; Bello, Nancy; Becker, Jennifer; Zangeneh, Tirdad

    2015-01-01

    Granulomatous amoebic encephalitis (GAE) due to Acanthamoeba is almost a uniformly fatal infection in immune-compromised hosts despite multidrug combination therapy. We report a case of GAE in a female who received a deceased donor kidney graft. She was treated with a combination of miltefosine, pentamidine, sulfadiazine, fluconazole, flucytosine, and azithromycin. PMID:26280011

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

    PubMed

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

    2016-05-01

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

  3. Cyclooxygenase activity contributes to the monoaminergic damage caused by serial exposure to stress and methamphetamine.

    PubMed

    Northrop, Nicole A; Yamamoto, Bryan K

    2013-09-01

    Methamphetamine (Meth) is a widely abused psychostimulant that causes long-term dopamine (DA) and serotonin (5-HT) depletions. Stress and Meth abuse are comorbid events in society and stress exacerbates Meth-induced monoaminergic terminal damage. Stress is also known to produce neuroinflammation. This study examined the role of the neuroinflammatory mediator, cyclooxygenase (COX), in the depletions of monoamines caused by serial exposure to chronic unpredictable stress (CUS) and Meth. CUS produced an increase in COX-2 protein expression and enhanced Meth-induced monoaminergic depletions in the striatum and hippocampus. The enhanced DA and 5-HT depletions in the striatum, but not the hippocampus, were prevented by pretreatment with COX inhibitor, ketoprofen, during stress or during Meth; however, ketoprofen did not attenuate the monoaminergic damage caused by Meth alone. The COX-dependent enhancement by stress of Meth-induced monoaminergic depletions was independent of hyperthermia, as ketoprofen did not attenuate Meth-induced hyperthermia. In addition, the EP1 receptor antagonist, SC-51089, did not attenuate DA or 5-HT depletions caused by stress and Meth. These findings illustrate that COX activity, but not activation of the EP1 receptor, is responsible for the potentiation of Meth-induced damage to striatal monoamine terminals by stress and suggests the use of anti-inflammatory drugs for mitigating the neurotoxic effects associated with the combination of stress and Meth.

  4. Remote conditioning or erythropoietin before surgery primes kidneys to clear ischemia-reperfusion-damaged cells: a renoprotective mechanism?

    PubMed

    Gardner, David S; Welham, Simon J M; Dunford, Louise J; McCulloch, Thomas A; Hodi, Zsolt; Sleeman, Philippa; O'Sullivan, Saoirse; Devonald, Mark A J

    2014-04-15

    Acute kidney injury is common, serious with no specific treatment. Ischemia-reperfusion is a common cause of acute kidney injury (AKI). Clinical trials suggest that preoperative erythropoietin (EPO) or remote ischemic preconditioning may have a renoprotective effect. Using a porcine model of warm ischemia-reperfusion-induced AKI (40-min bilateral cross-clamping of renal arteries, 48-h reperfusion), we examined the renoprotective efficacy of EPO (1,000 iu/kg iv.) or remote ischemic preconditioning (3 cycles, 5-min inflation/deflation to 200 mmHg of a hindlimb sphygmomanometer cuff). Ischemia-reperfusion induced significant kidney injury at 24 and 48 h (χ(2), 1 degree of freedom, >10 for 6/7 histopathological features). At 2 h, a panel of biomarkers including plasma creatinine, neutrophil gelatinase-associated lipocalin, and IL-1β, and urinary albumin:creatinine could be used to predict histopathological injury. Ischemia-reperfusion increased cell proliferation and apoptosis in the renal cortex but, for pretreated groups, the apoptotic cells were predominantly intratubular rather than interstitial. At 48-h reperfusion, plasma IL-1β and the number of subcapsular cells in G2-M arrest were reduced after preoperative EPO, but not after remote ischemic preconditioning. These data suggest an intrarenal mechanism acting within cortical cells that may underpin a renoprotective function for preoperative EPO and, to a limited extent, remote ischemic preconditioning. Despite equivocal longer-term outcomes in clinical studies investigating EPO as a renoprotective agent in AKI, optimal clinical dosing and administration have not been established. Our data suggest further clinical studies on the potential renoprotective effect of EPO and remote ischemic preconditioning are justified.

  5. Exposure to Silica Nanoparticles Causes Reversible Damage of the Spermatogenic Process in Mice

    PubMed Central

    Yu, Yang; Li, Yang; Li, Yan-Bo; Yu, Yong-Bo; Zhou, Xian-Qing; Sun, Zhi-Wei

    2014-01-01

    Environmental exposure to nanomaterials is inevitable, as nanomaterials have become part of our daily life now. In this study, we firstly investigated the effects of silica nanoparticles on the spermatogenic process according to their time course in male mice. 48 male mice were randomly divided into control group and silica nanoparticle group with 24 mice per group, with three evaluation time points (15, 35 and 60 days after the first dose) per group. Mice were exposed to the vehicle control and silica nanoparticles at a dosage of 20 mg/kg every 3 days, five times over a 13-day period, and were sacrificed at 15, 35 and 60 days after the first dose. The results showed that silica nanoparticles caused damage to the mitochondrial cristae and decreased the levels of ATP, resulting in oxidative stress in the testis by days 15 and 35; however, the damage was repaired by day 60. DNA damage and the decreases in the quantity and quality of epididymal sperm were found by days 15 and 35; but these changes were recovered by day 60. In contrast, the acrosome integrity and fertility in epididymal sperm, the numbers of spermatogonia and sperm in the testes, and the levels of three major sex hormones were not significantly affected throughout the 60-day period. The results suggest that nanoparticles can cause reversible damage to the sperms in the epididymis without affecting fertility, they are more sensitive than both spermatogonia and spermatocytes to silica nanoparticle toxicity. Considering the spermatogenesis time course, silica nanoparticles primarily influence the maturation process of sperm in the epididymis by causing oxidative stress and damage to the mitochondrial structure, resulting in energy metabolism dysfunction. PMID:25003337

  6. Identification of high-risk population and prevalence of kidney damage among asymptomatic central government employees in Delhi, India.

    PubMed

    Mahapatra, Himanshu Sekhar; Gupta, Yadunanandan Prasad; Sharma, Neera; Buxi, Gurdeep

    2016-03-01

    Chronic kidney disease (CKD) has attained epidemic proportions in India due to increased incidence of diabetes and hypertension (HTN). It was surmised that identification of only high-risk groups (HRGs) through a questionnaire would be sufficient to identify cases of kidney damage (KD). The study attempted to device a questionnaire to classify the subjects in to HRG and low-risk group (LRG) and assess the extent of early KD. The central government employees were classified into HRG and LRG based on "SCreening for Occult REnal Disease (SCORED)" and "EXTENDED" questionnaire formulated after addition of 10 more parameters apart from diabetes and HTN. Urine examination by dipstick, quantitative microalbumin, serum creatinine, and estimated glomerular filtration rate were assessed to determine KD. The data were analyzed for risk-group classification. Sensitivity was calculated based on the number of KD cases in the HRG. Of the 1104 employees screened, 58% and 42% were classified in HRG and LRG, respectively. There were 306 KD cases of whom, 65% were in the HRG. The sensitivity of the EXTENDED questionnaire to detect CKD was much higher (60%) compared to the SCORED questionnaire (25%). The prevalence of KD according to stage was: stage-1, 13.4%; stage-2, 9.9%; and late stages (3, 4, and 5), 4.5%. Microalbuminuria and dipstick-positive proteinuria showed statistically higher proportion in the HRG (25% and 4.1%) than in the LRG (19% and 1%, respectively) (P <0.05). Although the EXTENDED questionnaire was more sensitive in detecting KD, only screening the high-risk population will leave behind 35% of KD cases. There is, therefore, a need for mass screening at regular intervals.

  7. White and dark kidney beans reduce colonic mucosal damage and inflammation in response to dextran sodium sulfate.

    PubMed

    Monk, Jennifer M; Zhang, Claire P; Wu, Wenqing; Zarepoor, Leila; Lu, Jenifer T; Liu, Ronghua; Pauls, K Peter; Wood, Geoffrey A; Tsao, Rong; Robinson, Lindsay E; Power, Krista A

    2015-07-01

    Common beans are a rich source of nondigestible fermentable components and phenolic compounds that have anti-inflammatory effects. We assessed the gut-health-promoting potential of kidney beans in healthy mice and their ability to attenuate colonic inflammation following dextran sodium sulphate (DSS) exposure (via drinking water, 2% DSS w/v, 7 days). C57BL/6 mice were fed one of three isocaloric diets: basal diet control (BD), or BD supplemented with 20% cooked white (WK) or dark red kidney (DK) bean flour for 3 weeks. In healthy mice, anti-inflammatory microbial-derived cecal short chain fatty acid (SCFA) levels (acetate, butyrate and propionate), colon crypt height and colonic Mucin 1 (MUC1) and Resistin-like Molecule beta (Relmβ) mRNA expression all increased in WK- and DK-fed mice compared to BD, indicative of enhanced microbial activity, gut barrier integrity and antimicrobial defense response. During colitis, both bean diets reduced (a) disease severity, (b) colonic histological damage and (c) increased mRNA expression of antimicrobial and barrier integrity-promoting genes (Toll-like Receptor 4 (TLR4), MUC1-3, Relmβ and Trefoil Factor 3 (TFF3)) and reduced proinflammatory mediator expression [interleukin (IL)-1β, IL-6, interferon (IFN)γ, tumor necrosis factor (TNF)α and monocyte chemoattractant protein-1], which correlated with reduced colon tissue protein levels. Further, bean diets exerted a systemic anti-inflammatory effect during colitis by reducing serum levels of IL-17A, IFNγ, TNFα, IL-1β and IL-6. In conclusion, both WK and DK bean-supplemented diets enhanced microbial-derived SCFA metabolite production, gut barrier integrity and the microbial defensive response in the healthy colon, which supported an anti-inflammatory phenotype during colitis. Collectively, these data demonstrate a beneficial colon-function priming effect of bean consumption that mitigates colitis severity.

  8. ANALYSIS OF DAMAGE TO WASTE PACKAGES CAUSED BY SEISMIC EVENTS DURING POST-CLOSURE

    SciTech Connect

    Alves, S W; Blair, S C; Carlson, S R; Gerhard, M; Buscheck, T A

    2008-05-27

    This paper presents methodology and results of an analysis of damage due to seismic ground motion for waste packages emplaced in a nuclear waste repository at Yucca Mountain, Nevada. A series of three-dimensional rigid body kinematic simulations of waste packages, pallets, and drip shields subjected to seismic ground motions was performed. The simulations included strings of several waste packages and were used to characterize the number, location, and velocity of impacts that occur during seismic ground motion. Impacts were categorized as either waste package-to-waste package (WP-WP) or waste package-to-pallet (WP-P). In addition, a series of simulations was performed for WP-WP and WP-P impacts using a detailed representation of a single waste package. The detailed simulations were used to determine the amount of damage from individual impacts, and to form a damage catalog, indexed according to the type, angle, location and force/velocity of the impact. Finally, the results from the two analyses were combined to estimate the total damage to a waste package that may occur during an episode of seismic ground motion. This study addressed two waste package types, four levels of peak ground velocity (PGV), and 17 ground motions at each PGV. Selected aspects of waste package degradation, such as effective wall thickness and condition of the internals, were also considered. As expected, increasing the PGV level of the vibratory ground motion increases the damage to the waste packages. Results show that most of the damage is caused by WP-P impacts. TAD-bearing waste packages with intact internals are highly resistant to damage, even at a PGV of 4.07 m/s, which is the highest level analyzed.

  9. Severe mortality in wild Atlantic salmon Salmo salar due to proliferative kidney disease (PKD) caused by Tetracapsuloides bryosalmonae (myxozoa).

    PubMed

    Sterud, Erik; Forseth, Torbjørn; Ugedal, Ola; Poppe, Trygve T; Jørgensen, Anders; Bruheim, Torkjell; Fjeldstad, Hans-Petter; Mo, Tor Atle

    2007-10-15

    Extensive mortality in Atlantic salmon fry was reported in the River Aelva from 2002 to 2004. Dead fish were collected in late summer 2006, and live fish were sampled by electrofishing in September the same year. At autopsy and in histological sections, the fish kidneys were found to be pale and considerably enlarged. Proliferative lesions with characteristic PKX cells were seen in a majority of the fish. DNA from kidney samples of diseased fish was subjected to PCR and sequencing, and the amplified sequences matched those of Tetracapsuloides bryosalmonae. We concluded that this myxozoan transmitted from bryozoans was the main cause of the observed mortality in salmon fry in 2006. Results from quantitative electrofishing in 2005 and 2006, combined with the observed fry mortality from 2002 to 2004, show that the smolt production in the river is severely reduced and that T. bryosalmonae is the most likely explanation for this decline. The present study is the first to report a considerable negative population effect in wild Atlantic salmon due to proliferative kidney disease (PKD). It also represents the northernmost PKD outbreak in wild fish. The river is regulated for hydroelectric power purposes, causing reduced water flow and elevated summer temperatures, and the present PKD outbreak may serve as an example of increased disease vulnerability of northern fish populations in a warmer climate.

  10. Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

    SciTech Connect

    Arriba, G. de Perez de Hornedo, J.; Ramirez Rubio, S.; Calvino Fernandez, M.; Benito Martinez, S.; Maiques Camarero, M.; Parra Cid, T.

    2009-09-15

    Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry and confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondria.

  11. [Forensic medical characteristics of the damages to the human clothes caused by blowgun shots of various types of darts].

    PubMed

    Makarov, I Yu; Baibarza, N V; Lorents, A S

    2016-01-01

    The objective of the present experimental study was to determine certain regular features of the damages to the human clothes caused by blowgun shots of various types of darts and to elucidate the mechanisms underlying the formation of the damages. The study revealed the objective morphological features of the damages inflicted by various types of darts shot from the blowguns of two calibers.

  12. Extensive facial damage caused by a blast injury arising from a 6 volt lead accumulator.

    PubMed

    Singh, S K; Jain, P; Sinha, J K

    1999-03-01

    Low-voltage electrical injuries are relatively uncommon. Injury caused by flow of heavy current due to short-circuiting a low-voltage battery has not been described in the English literature. A 9-year-old boy connected two thin household electrical wires to the two terminals of a 6 volt (lead accumulator) battery and pressed the other two ends between his teeth. This resulted in a blast causing a compound comminuted fracture of the mandible and extensive tissue damage in the oral cavity. The low internal resistance of a lead accumulator (approximately 0.03 ohms) permits the flow of a heavy current (approximately 200 amps) when short-circuited. This instantaneously vaporises a minuscule portion of wire at approximately 2000 K resulting in a sudden rise of intraoral pressure to 30 kg cm-2 leading to tissue damage.

  13. Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA

    PubMed Central

    Gao, Qiuqiang; Liou, Liang-Chun; Ren, Qun; Bao, Xiaoming; Zhang, Zhaojie

    2014-01-01

    The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ0). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS). Also, SCW11 mRNA levels are elevated in ρ0 cells. Deletion of SCW11 significantly decreases the sensitivity of ρ0 cells to SDS after salt treatment, while overexpression of SCW11 results in higher sensitivity. In addition, salt stress in ρ0 cells induces high levels of reactive oxygen species (ROS), which further damages the cell wall, causing cells to become more sensitive towards the cell wall-perturbing agent. PMID:28357227

  14. Kidney Dysplasia

    MedlinePlus

    ... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

  15. Experimental Investigation of Widespread Delamination Damage to Composite Materials Caused by Radiant Heating

    DTIC Science & Technology

    2013-06-30

    epoxy laminate fiberglass stock material bonded with epoxy resin (Armstrong A-12). After manufacture, plates were stored at room temperature and...sell any patented invention that may relate to them. This report was cleared for public release by the...delamination damage caused by the thermal environment. Three classes of matrix resins were evaluated with IM7 carbon fibers; epoxy 977-3, modified

  16. Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage

    PubMed Central

    Vermeulen Windsant, Iris C.; de Wit, Norbert C. J.; Sertorio, Jonas T. C.; van Bijnen, Annemarie A.; Ganushchak, Yuri M.; Heijmans, John H.; Tanus-Santos, Jose E.; Jacobs, Michael J.; Maessen, Jos G.; Buurman, Wim A.

    2014-01-01

    Introduction: Acute kidney injury (AKI) and intestinal injury negatively impact patient outcome after cardiac surgery. Enhanced nitric oxide (NO) consumption due to intraoperative intravascular hemolysis, may play an important role in this setting. This study investigated the impact of hemolysis on plasma NO consumption, AKI, and intestinal tissue damage, after cardiac surgery. Methods: Hemolysis (by plasma extracellular (free) hemoglobin; fHb), plasma NO-consumption, plasma fHb-binding capacity by haptoglobin (Hp), renal tubular injury (using urinary N-Acetyl-β-D-glucosaminidase; NAG), intestinal mucosal injury (through plasma intestinal fatty acid binding protein; IFABP), and AKI were studied in patients undergoing off-pump cardiac surgery (OPCAB, N = 7), on-pump coronary artery bypass grafting (CABG, N = 30), or combined CABG and valve surgery (CABG+Valve, N = 30). Results: FHb plasma levels and NO-consumption significantly increased, while plasma Hp concentrations significantly decreased in CABG and CABG+Valve patients (p < 0.0001) during surgery. The extent of hemolysis and NO-consumption correlated significantly (r2 = 0.75, p < 0.0001). Also, NAG and IFABP increased in both groups (p < 0.0001, and p < 0.001, respectively), and both were significantly associated with hemolysis (Rs = 0.70, p < 0.0001, and Rs = 0.26, p = 0.04, respectively) and NO-consumption (Rs = 0.55, p = 0.002, and Rs = 0.41, p = 0.03, respectively), also after multivariable logistic regression analysis. OPCAB patients did not show increased fHb, NO-consumption, NAG, or IFABP levels. Patients suffering from AKI (N = 9, 13.4%) displayed significantly higher fHb and NAG levels already during surgery compared to non-AKI patients. Conclusions: Hemolysis appears to be an important contributor to postoperative kidney injury and intestinal mucosal damage, potentially by limiting NO-bioavailability. This observation offers a novel diagnostic and therapeutic target to improve patient outcome after

  17. A potential cause for kidney stone formation during space flights: enhanced growth of nanobacteria in microgravity

    NASA Technical Reports Server (NTRS)

    Ciftcioglu, Neva; Haddad, Ruwaida S.; Golden, D. C.; Morrison, Dennis R.; McKay, David S.

    2005-01-01

    BACKGROUND: Although some information is available regarding the cellular/molecular changes in immune system exposed to microgravity, little is known about the reasons of the increase in the kidney stone formation in astronauts during and/or after long duration missions at zero gravity (0 g). In our earlier studies, we have assessed a unique agent, nanobacteria (NB), in kidney stones and hypothesized that NB have an active role in calcium phosphate-carbonate deposition in kidney. In this research we studied effect of microgravity on multiplication and calcification of NB in vitro. METHODS: We examined NB cultures in High Aspect Rotating Vessels (HARVs) designed at the NASA's Johnson Space Center, which are designed to stimulate some aspects of microgravity. Multiplication rate and calcium phosphate composition of those NB were compared with NB cultured on stationary and shaker flasks. Collected aliquots of the cultures from different incubation periods were analyzed using spectrophotometer, SEM, TEM, EDX, and x-ray diffraction techniques. RESULTS: The results showed that NB multiplied 4.6x faster in HARVs compared to stationary cultures, and 3.2x faster than shaker flask conditions. X-ray diffraction and EDX analysis showed that the degree of apatite crystal formation and the properties of the apatite depend on the specific culture conditions used. CONCLUSION: We now report an increased multiplication rate of NB in microgravity-simulated conditions. Thus, NB infection may have a potential role in kidney stone formation in crew members during space flights. For further proof to this hypothesis, screening of the NB antigen and antibody level in flight crew before and after flight would be necessary.

  18. Spectrum of glomerular diseases causing acute kidney injury; 25 years experience from a single center

    PubMed Central

    Naqvi, Rubina; Mubarak, Muhammed; Ahmed, Ejaz; Akhtar, Fazal; Bhatti, Sajid; Naqvi, Anwar; Rizvi, Adib

    2015-01-01

    Introduction: Acute kidney injury (AKI) is common in nephro-urological practice. Its incidence, prevalence and etiology vary widely, mainly due to variations in the definitions of AKI. Objectives: We aim to report the spectrum of glomerular diseases presenting as AKI at a kidney referral center in Pakistan. Patients and Methods: An observational cohort of patients identified as having AKI which was defined according to RIFLE criteria, with normal size, non-obstructed kidneys on ultrasonography, along with active urine sediment, edema and new onset hypertension. Results: From 1990 to 2014, 236 cases of AKI secondary to acute glomerulonephritis (AGN) registered at this institution. Mean age of patients was 27.94± 12.79 years and M:F ratio was 0.77:1. Thirty percent patients revealed crescents on renal biopsy. AGN without crescents was seen in 33.05% of cases. Postinfectious GN was found in 14.4%, lupus nephritis in 8.5% and mesangiocapillary GN in 3.4% cases. Renal replacement therapy (RRT) required in 75.84% patients. Pulse steroids were given in 45.33% cases followed by oral steroids. Pulse cyclophoshphamide was given in 23.7% cases and plasmapheresis was used in 3.38% cases. Complete recovery was seen in 44%, while 11.44% died during acute phase of illness. About 19.49 % developed chronic kidney disease (CKD) and 25.84% were lost to long- term follow-up. Conclusion: Although glomerular diseases contribute only 4.19 % of total AKI at this center, morbidity associated with illness and its treatment is more marked than other AKI groups. Another notable factor is late referral of these patients to specialized centers resulting in undesirable outcome. PMID:26693497

  19. Modulating effect of Allium cepa on kidney apoptosis caused by Toxoplasma gondii

    PubMed Central

    Gharadaghi, Yaghub; Shojaee, Saeedeh; Khaki, Arash; Hatef, Amir; Ahmadi Ashtiani, Hamid Reza; Rastegar, Hossin; Fathiazad, Fatemeh

    2012-01-01

    Purpose: Toxoplasma gondii is a widespread protozoan parasite that infects a broad range of warm blooded animals as well as humans. The present study was investigated to evaluate the effects of allium cepa on renal failur in male rats which experimentally infected by Toxoplasma gondii, RH strain. Methods: Wistar male rat (n=40) were allocated into four groups, group one that received tachyzoites of T. gondii (ip) (n=10), group two that received tachyzoites of T. gondii (ip), plus fresh onion juice by gavages method (n=10), group three received just fresh onion juice by gavages method (n=10) and control group (n=10) that received nothing. Animals were kept in standard condition. In 30 day after inducing Toxoplasma infection, 5cc blood was collected for serum protein and TAC levels. Kidney tissues of Rat in whole groups were removed and prepared for apopetosis analysis. Results: Serum protein and kidneys weights were significantly decreased in groups that were infected with T. gondii, in comparison to control and onions groups. Kidneys Apopetosis in toxoplasma group significantly increased in comparison to control group (P<0.05).level of TAC was significantly increased in groups that received onio juice (P<0.05). Conclusion: This study showed that T. gondii have significantly effect on serum protein and TAC, apopetosis and fresh onion juice returned and treated this harmful effect, so it is suggested that eating of onion is useful in toxoplasma infection. PMID:24312764

  20. Caffeic acid phenethyl ester as a protective agent against nephrotoxicity and/or oxidative kidney damage: a detailed systematic review.

    PubMed

    Akyol, Sumeyya; Ugurcu, Veli; Altuntas, Aynur; Hasgul, Rukiye; Cakmak, Ozlem; Akyol, Omer

    2014-01-01

    Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R). In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility.

  1. Caffeic Acid Phenethyl Ester as a Protective Agent against Nephrotoxicity and/or Oxidative Kidney Damage: A Detailed Systematic Review

    PubMed Central

    Akyol, Sumeyya; Ugurcu, Veli; Altuntas, Aynur; Hasgul, Rukiye; Cakmak, Ozlem

    2014-01-01

    Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R). In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility. PMID:25003138

  2. NLRP3 inflammasome activation is involved in Ang II-induced kidney damage via mitochondrial dysfunction

    PubMed Central

    Wen, Yi; Liu, Yiran; Tang, Taotao; Lv, Linli; Liu, Hong; Ma, Kunling; Liu, Bicheng

    2016-01-01

    Growing evidence has shown that NLRP3 inflammasome activation promotes the development of tubulointerstitial inflammation and progression of renal injury. We previously found that mitochondrial dysfunction is a critical determinant for the activation of NLRP3 inflammasome in albumin-overload rats. Angiotensin (Ang) II plays an important role in mitochondrial homeostasis. Here, we investigated the role of Ang II in NLRP3 inflammasome activation and the involvement of mitochondrial dysfunction in this process. In vitro, Ang II triggered NLRP3 inflammasome activation in a dose- and time-dependent manner, and this effect is mediated by AT1 receptor rather than AT2 receptor. MitoTEMPO, a mitochondrial targeted antioxidant, attenuated Ang II induced mitochondrial reactive oxygen species (mROS) production and NLRP3 inflammation activation. Following chronic Ang II infusion for 28 days, we observed remarkable tubular epithelial cells (TECs) injury, mitochondrial damage, and albuminuria in WT mice. However, these abnormalities were significantly attenuated in AT1 receptor KO mice. Then, we examined the role of mitochondria in Ang II-infused mice with or without mitoTEMPO treatment. As expected, Ang II-induced mitochondrial dysfunction and NLRP3 inflammasome activation was markedly inhibited by mitoTEMPO. Notably, NLRP3 deletion signally protected TECs from Ang II-triggered mitochondrial dysfunction and NLRP3 inflammasome activation. Taken together, these data demonstrate that Ang II induces NLRP3 inflammasome activation in TECs which is mediated by mitochondrial dysfunction. PMID:27509058

  3. Damage to lens fiber cells causes TRPV4-dependent Src family kinase activation in the epithelium.

    PubMed

    Shahidullah, M; Mandal, A; Delamere, N A

    2015-11-01

    The bulk of the lens consists of tightly packed fiber cells. Because mature lens fibers lack mitochondria and other organelles, lens homeostasis relies on a monolayer of epithelial cells at the anterior surface. The detection of various signaling pathways in lens epithelial cells suggests they respond to stimuli that influence lens function. Focusing on Src Family Kinases (SFKs) and Transient Receptor Potential Vanilloid 4 (TRPV4), we tested whether the epithelium can sense and respond to an event that occurs in fiber mass. The pig lens was subjected to localized freeze-thaw (FT) damage to fibers at posterior pole then the lens was incubated for 1-10 min in Krebs solution at 37 °C. Transient SFK activation in the epithelium was detectable at 1 min. Using a western blot approach, the ion channel TRPV4 was detected in the epithelium but was sparse or absent in fiber cells. Even though TRPV4 expression appears low at the actual site of FT damage to the fibers, SFK activation in the epithelium was suppressed in lenses subjected to FT damage then incubated with the TRPV4 antagonist HC067047 (10 μM). Na,K-ATPase activity was examined because previous studies report changes of Na,K-ATPase activity associated with SFK activation. Na,K-ATPase activity doubled in the epithelium removed from FT-damaged lenses and the response was prevented by HC067047 or the SFK inhibitor PP2 (10 μM). Similar changes were observed in response to fiber damage caused by injection of 5 μl hyperosmotic NaCl or mannitol solution beneath the surface of the posterior pole. The findings point to a TRPV4-dependent mechanism that enables the epithelial cells to detect remote damage in the fiber mass and respond within minutes by activating SFK and increasing Na,K-ATPase activity. Because TRPV4 channels are mechanosensitive, we speculate they may be stimulated by swelling of the lens structure caused by damage to the fibers. Increased Na,K-ATPase activity gives the lens greater capacity to

  4. Urinary CD133+ Extracellular Vesicles Are Decreased in Kidney Transplanted Patients with Slow Graft Function and Vascular Damage

    PubMed Central

    Dimuccio, Veronica; Ranghino, Andrea; Praticò Barbato, Loredana; Fop, Fabrizio; Biancone, Luigi; Camussi, Giovanni; Bussolati, Benedetta

    2014-01-01

    Extracellular vesicles (EVs) present in the urine are mainly released from cells of the nephron and can therefore provide information on kidney function. We here evaluated the presence of vesicles expressing the progenitor marker CD133 in the urine of normal subjects and of patients undergoing renal transplant. We found that EV expressing CD133 were present in the urine of normal subjects, but not of patients with end stage renal disease. The first day after transplant, urinary CD133+ EVs were present at low levels, to increase thereafter (at day 7). Urinary CD133+ EVs significantly increased in patients with slow graft function in respect to those with early graft function. In patients with a severe pre-transplant vascular damage of the graft, CD133+ EVs did not increase at day 7. At variance, the levels of EVs expressing the renal exosomal marker CD24 did not vary in the urine of patients with end stage renal disease or in transplanted patients in respect to controls. Sorted CD133+ EVs were found to express glomerular and proximal tubular markers. These data indicate that urinary CD133+ EVs are continuously released during the homeostatic turnover of the nephron and may provide information on its function or regenerative potential. PMID:25100147

  5. Low level exposure to weathered crude oil causes genetic damage and malformations in larval herring

    SciTech Connect

    Carls, M.; Rice, S.D.; Hose, J.E.

    1995-12-31

    An initial concentration of 0.7 ppb polycyclic aromatic hydrocarbons (PAHs) in weathered Alaska North Slope crude oil caused genetic damage in newly hatched Pacific herring (Clupea pallasi) exposed for 16 days during incubation. The endpoint for genetic damage was a significant increase in the percentage of anaphase aberrations in pectoral fin cells, a response that has been previously shown to be a highly sensitive indicator of crude oil exposure in larval herring. At this exposure level, there were also significant decreases in the percentages of larval survival, normal development and competent swimming, and increased percentages of yolk sac edema. Composition of the PAH, which ranged from naphthalenes through chrysenes, was weighted toward the larger ring compounds, particularly phenanthrenes. Genetic response was not as sensitive an indicator of oil exposure as yolk sac edema, jaw size, and formation of pectoral fin rays. The consequences of chromosomal aberrations in larval herring are not clear. Other experiments have shown that although the frequency of genetic damage decreases with age, malformations persist and are coupled with growth reductions. It is likely that malformed larvae die; evidence for this comes from simultaneous measurements of mortality, malformations and genetic damage in the field.

  6. A systematic approach for the prevention and treatment of formation damage caused by asphaltene deposition

    SciTech Connect

    Leontaritis, K.J.; Amaefule, J.O.; Charles, R.E. )

    1994-08-01

    Asphaltene plugging is a known cause of near-wellbore formation damage. Deposited asphaltenes can reduce effective hydrocarbon mobility by (1) blocking the pore throats; (2) adsorbing onto the rock, thereby altering the formation wettability from water-wet to oil-wet; and (3) increasing hydrocarbon viscosity by nucleating water-in-oil emulsions. Asphaltene flocculation and deposition can be avoided in some, but not all, cases. Some formation damage resulting from asphaltene plugging is permanent and hence must be prevented rather than treated. Prevention of asphaltene-induced formation damage should be started in the early stages of drilling and well completion, once the oil is known to be asphaltenic. This paper presents a systematic approach to successful diagnosis, prevention, and mitigation of asphaltene problems during recovery of asphaltenic oils. A mechanism of asphaltene flocculation and deposition is proposed and analyzed, and the previously defined concept of asphaltene deposition envelope is further refined. Diagnostic technology is presented that can test the compatibility of drilling and completion fluids with any asphaltenic oil. Important issues that need to be considered in the design of treatments for asphaltene removal are discussed. Finally, the paper presents a methodology for restoring unfavorable wettability changes caused by asphaltene deposition.

  7. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility

    NASA Astrophysics Data System (ADS)

    Bai, Yuhong; Zhang, Yi; Zhang, Jingping; Mu, Qingxin; Zhang, Weidong; Butch, Elizabeth R.; Snyder, Scott E.; Yan, Bing

    2010-09-01

    Soluble carbon nanotubes show promise as materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, but their effects on male reproduction have not been examined. Here, we show that repeated intravenous injections of water-soluble multiwalled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired at 60 and 90 days. The quantity, quality and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice.

  8. Assessing the damage caused by Deepwater Horizon: not just another Exxon Valdez.

    PubMed

    Perrons, Robert K

    2013-06-15

    In light of the high stakes of the Deepwater Horizon civil trial and the important precedent-setting role that the case will have on the assessment of future marine disasters, the methodologies underpinning the calculations of damage on both sides will be subjected to considerable scrutiny. Despite the importance of the case, however, there seems to be a pronounced lack of convergence about it in the academic literature. Contributions from scientific journals frequently make comparisons to the Ixtoc I oil spill off the coast of Mexico in 1979; the legal literature, by stark contrast, seems to be much more focused on the Exxon Valdez spill that occurred off the shores of Alaska in 1989. This paper accordingly calls for a more thorough consideration of other analogs beyond the Exxon Valdez spill-most notably, the Ixtoc I incident-in arriving at an assessment of the damage caused by the Deepwater Horizon disaster.

  9. Localized-impact damage caused by proton bombarding in mercury target

    NASA Astrophysics Data System (ADS)

    Futakawa, M.; Kogawa, H.; Ishikura, S.; Kyudo, H.; Soyama, H.

    2003-09-01

    A liquid-mercury target system for the MW-scale target is being developed in the world. The moment the proton beams bombard the target, stress waves will be imposed on the beam window and pressure waves will be generated in the mercury by the thermally shocked heat deposition. Provided that the negative pressure generates through its propagation in the mercury target and causes cavitation in the mercury, there is the possibility for the cavitation bubbles collapse to form pits on the interface between the mercury and the target vessel wall. In order to estimate the cavitation erosion damage off-line tests were performed using Split Hopkinson Pressure Bar (SHPB) technique. It was confirrned through the experiments that the pitfing damage is suppressed by surface hardening treatments : Kolsterising, coatings, etc. Relative hardness appears to be a good correlating parameter on impact erosion resistance evaluated by the SHBP and conventional vibratory hone tests.

  10. Repeated carbon nanotube administrations in male mice cause reversible testis damage without affecting fertility

    PubMed Central

    Bai, Yuhong; Zhang, Yi; Zhang, Jingping; Mu, Qingxin; Zhang, Weidong; Butch, Elizabeth R.; Snyder, Scott E.; Yan, Bing

    2010-01-01

    Soluble carbon nanotubes are promising materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, however, their effects on male reproduction have not been examined. Here we show that repeated intravenous injections of water-soluble multi-walled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress, and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired after 60 and 90 days. The quantity, quality, and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice. PMID:20693989

  11. Thrombotic microangiopathy caused by oral contraceptives in a kidney transplant recipient.

    PubMed

    Shirai, Hiroyuki; Yashima, Jun; Tojimbara, Tamotsu; Honda, Kazuho

    2016-07-01

    Thrombotic microangiopathy (TMA) after kidney transplantation has various aetiologies, including acute antibody-mediated rejection, bacterial or viral infection and immunosuppressive drugs, particularly calcineurin inhibitors. We present the case of a 28-year-old woman who developed TMA 30 months after the transplantation of an ABO-incompatible kidney from a living unrelated donor. The patient developed a sudden onset of allograft renal dysfunction and became uremic. She was transferred to our institution from a community hospital with strongly suspected acute allograft rejection. Intensive treatments for both T- and B-cell mediated acute rejection, including steroid pulse therapy, double-filtration plasmapheresis, antithymocyte globulin (1.5 mg/kg × 14 days) and rituximab (100 mg), were initiated during haemodialysis. However, her renal allograft function did not improve. Histopathological analysis 8 days after the treatment indicated TMA, despite the absence of apparent acute T-cell- or acute antibody-mediated rejection. There were no symptoms of infectious diseases, such as intestinal haemorrhagic colitis or viral infection. We concluded that the use of oral contraceptives, which had been initiated 3 weeks before TMA onset for the treatment of irregular vaginal bleeding, was the aetiologic agent.

  12. The isolated perfused kidney: an in vitro test system for evaluation of renal tissue damage induced by high-energy shockwaves sources.

    PubMed

    Bergsdorf, Th; Thüroff, S; Chaussy, Ch

    2005-09-01

    Most of our knowledge of shockwave-induced renal damage is based on animal experiments and clinical observation. We developed a tissue model using isolated porcine kidneys perfused with Berliner Blau dye in physiologic saline using a Ureteromat Perez-Castro peristaltic pump connected to the renal artery. Reproducible results were obtained under a variety of experimental conditions. Further refinements of the model might consist of interposition of tissue layers in the shockwave path or simulation of ventilatory movements.

  13. Causes of excitation-induced muscle cell damage in isometric contractions: mechanical stress or calcium overload?

    PubMed

    Fredsted, Anne; Gissel, Hanne; Madsen, Klavs; Clausen, Torben

    2007-06-01

    Prolonged or unaccustomed exercise leads to muscle cell membrane damage, detectable as release of the intracellular enzyme lactic acid dehydrogenase (LDH). This is correlated to excitation-induced influx of Ca2+, but it cannot be excluded that mechanical stress contributes to the damage. We here explore this question using N-benzyl-p-toluene sulfonamide (BTS), which specifically blocks muscle contraction. Extensor digitorum longus muscles were prepared from 4-wk-old rats and mounted on holders for isometric contractions. Muscles were stimulated intermittently at 40 Hz for 15-60 min or exposed to the Ca2+ ionophore A23187. Electrical stimulation increased 45Ca influx 3-5 fold. This was followed by a progressive release of LDH, which was correlated to the influx of Ca2+. BTS (50 microM) caused a 90% inhibition of contractile force but had no effect on the excitation-induced 45Ca influx. After stimulation, ATP and creatine phosphate levels were higher in BTS-treated muscles, most likely due to the cessation of ATP-utilization for cross-bridge cycling, indicating a better energy status of these muscles. No release of LDH was observed in BTS-treated muscles. However, when exposed to anoxia, electrical stimulation caused a marked increase in LDH release that was not suppressed by BTS but associated with a decrease in the content of ATP. Dynamic passive stretching caused no increase in muscle Ca2+ content and only a minor release of LDH, whereas treatment with A23187 markedly increased LDH release both in control and BTS-treated muscles. In conclusion, after isometric contractions, muscle cell membrane damage depends on Ca2+ influx and energy status and not on mechanical stress.

  14. Evaluation of the damages caused by lightning current flowing through bearings

    NASA Technical Reports Server (NTRS)

    Celi, O.; Pigini, A.; Garbagnati, E.

    1991-01-01

    A laboratory for lightning current tests was set up allowing the generation of the lightning currents foreseen by the Standards. Lightning tests are carried out on different objects, aircraft materials and components, evaluating the direct and indirect effects of lightning. Recently a research was carried out to evaluate the effects of the lightning current flow through bearings with special reference to wind power generator applications. For this purpose, lightning currents of different amplitude were applied to bearings in different test conditions and the damages caused by the lightning current flow were analyzed. The influence of the load acting on the bearing, the presence of lubricant and the bearing rotation were studied.

  15. Methoxychlor causes mitochondrial dysfunction and oxidative damage in the mouse ovary

    SciTech Connect

    Gupta, R.K.; Schuh, R.A.; Fiskum, G.; Flaws, J.A. . E-mail: jflaws@epi.umaryland.edu

    2006-11-01

    Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in female rodents by causing ovarian atrophy, persistent estrous cyclicity, and antral follicle atresia (apoptotic cell death). Oxidative damage resulting from reactive oxygen species (ROS) generation has been demonstrated to lead to toxicant-induced cell death. Thus, this work tested the hypothesis that MXC causes oxidative damage to the mouse ovary and affects mitochondrial respiration in a manner that stimulates ROS production. For the in vitro experiments, mitochondria were collected from adult cycling mouse ovaries, treated with vehicle (dimethyl sulfoxide; DMSO) or MXC, and subjected to polarographic measurements of respiration. For the in vivo experiments, adult cycling CD-1 mice were dosed with either vehicle (sesame oil) or MXC for 20 days. After treatment, ovarian mitochondria were isolated and subjected to measurements of respiration and fluorimetric measurements of H{sub 2}O{sub 2} production. Some ovaries were also fixed and processed for immunohistochemistry using antibodies for ROS production markers: nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OHG). Ovaries from in vivo experiments were also used to measure the mRNA expression and activity of antioxidants such as Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX), and catalase (CAT). The results indicate that MXC significantly impairs mitochondrial respiration, increases production of H{sub 2}O{sub 2}, causes more staining for nitrotyrosine and 8-OHG in antral follicles, and decreases the expression and activity of SOD1, GPX, and CAT as compared to controls. Collectively, these data indicate that MXC inhibits mitochondrial respiration, causes ROS production, and decreases antioxidant expression and activity in the ovary, specifically in the antral follicles. Therefore, it is possible that MXC causes atresia of ovarian antral follicles by inducing oxidative stress through mitochondrial production of ROS.

  16. Deficiency of antidiuretic hormone: a rare cause of massive polyuria after kidney transplantation.

    PubMed

    Jang, Kyung Mi; Sohn, Young Soo; Hwang, Young Ju; Choi, Bong Seok; Cho, Min Hyun

    2016-04-01

    A 15-year-old boy, who was diagnosed with Alport syndrome and end-stage renal disease, received a renal transplant from a living-related donor. On postoperative day 1, his daily urine output was 10,000 mL despite normal graft function. His laboratory findings including urine, serum osmolality, and antidiuretic hormone levels showed signs similar to central diabetes insipidus, so he was administered desmopressin acetate nasal spray. After administering the desmopressin, urine specific gravity and osmolality increased abruptly, and daily urine output declined to the normal range. The desmopressin acetate was tapered gradually and discontinued 3 months later. Graft function was good, and urine output was maintained within the normal range without desmopressin 20 months after the transplantation. We present a case of a massive polyuria due to transient deficiency of antidiuretic hormone with the necessity of desmopressin therapy immediately after kidney transplantation in a pediatric patient.

  17. Causes and consequences of lipoprotein(a) abnormalities in kidney disease.

    PubMed

    Kronenberg, Florian

    2014-04-01

    Lipoprotein(a) is one of the strongest genetically determined risk factors for cardiovascular disease, and patients with chronic kidney disease have major disturbances in lipoprotein(a) metabolism. Concentrations are increased and are influenced by glomerular filtration rate (GFR) and the amount of proteinuria. The reason for this elevation can be increased synthesis, as is the case for patients with nephrotic syndrome or those treated by peritoneal dialysis. In hemodialysis patients, a catabolic block is the reason for this elevation. The elevated concentrations might contribute to the tremendous cardiovascular risk in this particular population. In particular, the genetically determined small apolipoprotein(a) isoforms are associated with an increased risk for cardiovascular events and total mortality.

  18. Copy-number disorders are a common cause of congenital kidney malformations.

    PubMed

    Sanna-Cherchi, Simone; Kiryluk, Krzysztof; Burgess, Katelyn E; Bodria, Monica; Sampson, Matthew G; Hadley, Dexter; Nees, Shannon N; Verbitsky, Miguel; Perry, Brittany J; Sterken, Roel; Lozanovski, Vladimir J; Materna-Kiryluk, Anna; Barlassina, Cristina; Kini, Akshata; Corbani, Valentina; Carrea, Alba; Somenzi, Danio; Murtas, Corrado; Ristoska-Bojkovska, Nadica; Izzi, Claudia; Bianco, Beatrice; Zaniew, Marcin; Flogelova, Hana; Weng, Patricia L; Kacak, Nilgun; Giberti, Stefania; Gigante, Maddalena; Arapovic, Adela; Drnasin, Kristina; Caridi, Gianluca; Curioni, Simona; Allegri, Franca; Ammenti, Anita; Ferretti, Stefania; Goj, Vinicio; Bernardo, Luca; Jobanputra, Vaidehi; Chung, Wendy K; Lifton, Richard P; Sanders, Stephan; State, Matthew; Clark, Lorraine N; Saraga, Marijan; Padmanabhan, Sandosh; Dominiczak, Anna F; Foroud, Tatiana; Gesualdo, Loreto; Gucev, Zoran; Allegri, Landino; Latos-Bielenska, Anna; Cusi, Daniele; Scolari, Francesco; Tasic, Velibor; Hakonarson, Hakon; Ghiggeri, Gian Marco; Gharavi, Ali G

    2012-12-07

    We examined the burden of large, rare, copy-number variants (CNVs) in 192 individuals with renal hypodysplasia (RHD) and replicated findings in 330 RHD cases from two independent cohorts. CNV distribution was significantly skewed toward larger gene-disrupting events in RHD cases compared to 4,733 ethnicity-matched controls (p = 4.8 × 10(-11)). This excess was attributable to known and novel (i.e., not present in any database or in the literature) genomic disorders. All together, 55/522 (10.5%) RHD cases harbored 34 distinct known genomic disorders, which were detected in only 0.2% of 13,839 population controls (p = 1.2 × 10(-58)). Another 32 (6.1%) RHD cases harbored large gene-disrupting CNVs that were absent from or extremely rare in the 13,839 population controls, identifying 38 potential novel or rare genomic disorders for this trait. Deletions at the HNF1B locus and the DiGeorge/velocardiofacial locus were most frequent. However, the majority of disorders were detected in a single individual. Genomic disorders were detected in 22.5% of individuals with multiple malformations and 14.5% of individuals with isolated urinary-tract defects; 14 individuals harbored two or more diagnostic or rare CNVs. Strikingly, the majority of the known CNV disorders detected in the RHD cohort have previous associations with developmental delay or neuropsychiatric diseases. Up to 16.6% of individuals with kidney malformations had a molecular diagnosis attributable to a copy-number disorder, suggesting kidney malformations as a sentinel manifestation of pathogenic genomic imbalances. A search for pathogenic CNVs should be considered in this population for the diagnosis of their specific genomic disorders and for the evaluation of the potential for developmental delay.

  19. Copy-Number Disorders Are a Common Cause of Congenital Kidney Malformations

    PubMed Central

    Sanna-Cherchi, Simone; Kiryluk, Krzysztof; Burgess, Katelyn E.; Bodria, Monica; Sampson, Matthew G.; Hadley, Dexter; Nees, Shannon N.; Verbitsky, Miguel; Perry, Brittany J.; Sterken, Roel; Lozanovski, Vladimir J.; Materna-Kiryluk, Anna; Barlassina, Cristina; Kini, Akshata; Corbani, Valentina; Carrea, Alba; Somenzi, Danio; Murtas, Corrado; Ristoska-Bojkovska, Nadica; Izzi, Claudia; Bianco, Beatrice; Zaniew, Marcin; Flogelova, Hana; Weng, Patricia L.; Kacak, Nilgun; Giberti, Stefania; Gigante, Maddalena; Arapovic, Adela; Drnasin, Kristina; Caridi, Gianluca; Curioni, Simona; Allegri, Franca; Ammenti, Anita; Ferretti, Stefania; Goj, Vinicio; Bernardo, Luca; Jobanputra, Vaidehi; Chung, Wendy K.; Lifton, Richard P.; Sanders, Stephan; State, Matthew; Clark, Lorraine N.; Saraga, Marijan; Padmanabhan, Sandosh; Dominiczak, Anna F.; Foroud, Tatiana; Gesualdo, Loreto; Gucev, Zoran; Allegri, Landino; Latos-Bielenska, Anna; Cusi, Daniele; Scolari, Francesco; Tasic, Velibor; Hakonarson, Hakon; Ghiggeri, Gian Marco; Gharavi, Ali G.

    2012-01-01

    We examined the burden of large, rare, copy-number variants (CNVs) in 192 individuals with renal hypodysplasia (RHD) and replicated findings in 330 RHD cases from two independent cohorts. CNV distribution was significantly skewed toward larger gene-disrupting events in RHD cases compared to 4,733 ethnicity-matched controls (p = 4.8 × 10−11). This excess was attributable to known and novel (i.e., not present in any database or in the literature) genomic disorders. All together, 55/522 (10.5%) RHD cases harbored 34 distinct known genomic disorders, which were detected in only 0.2% of 13,839 population controls (p = 1.2 × 10−58). Another 32 (6.1%) RHD cases harbored large gene-disrupting CNVs that were absent from or extremely rare in the 13,839 population controls, identifying 38 potential novel or rare genomic disorders for this trait. Deletions at the HNF1B locus and the DiGeorge/velocardiofacial locus were most frequent. However, the majority of disorders were detected in a single individual. Genomic disorders were detected in 22.5% of individuals with multiple malformations and 14.5% of individuals with isolated urinary-tract defects; 14 individuals harbored two or more diagnostic or rare CNVs. Strikingly, the majority of the known CNV disorders detected in the RHD cohort have previous associations with developmental delay or neuropsychiatric diseases. Up to 16.6% of individuals with kidney malformations had a molecular diagnosis attributable to a copy-number disorder, suggesting kidney malformations as a sentinel manifestation of pathogenic genomic imbalances. A search for pathogenic CNVs should be considered in this population for the diagnosis of their specific genomic disorders and for the evaluation of the potential for developmental delay. PMID:23159250

  20. Localized damage caused by topographic amplification during the 2010 M7.0 Haiti earthquake

    USGS Publications Warehouse

    Hough, S.E.; Altidor, J.R.; Anglade, D.; Given, D.; Janvier, M.G.; Maharrey, J.Z.; Meremonte, M.; Mildor, B.S.-L.; Prepetit, C.; Yong, A.

    2010-01-01

    Local geological conditions, including both near-surface sedimentary layers and topographic features, are known to significantly influence ground motions caused by earthquakes. Microzonation maps use local geological conditions to characterize seismic hazard, but commonly incorporate the effect of only sedimentary layers. Microzonation does not take into account local topography, because significant topographic amplification is assumed to be rare. Here we show that, although the extent of structural damage in the 2010 Haiti earthquake was primarily due to poor construction, topographic amplification contributed significantly to damage in the district of Petionville, south of central Port-au-Prince. A large number of substantial, relatively well-built structures situated along a foothill ridge in this district sustained serious damage or collapse. Using recordings of aftershocks, we calculate the ground motion response at two seismic stations along the topographic ridge and at two stations in the adjacent valley. Ground motions on the ridge are amplified relative to both sites in the valley and a hard-rock reference site, and thus cannot be explained by sediment-induced amplification. Instead, the amplitude and predominant frequencies of ground motion indicate the amplification of seismic waves by a narrow, steep ridge. We suggest that microzonation maps can potentially be significantly improved by incorporation of topographic effects. ?? 2010 Macmillan Publishers Limited. All rights reserved.

  1. v-Src Causes Chromosome Bridges in a Caffeine-Sensitive Manner by Generating DNA Damage.

    PubMed

    Ikeuchi, Masayoshi; Fukumoto, Yasunori; Honda, Takuya; Kuga, Takahisa; Saito, Youhei; Yamaguchi, Naoto; Nakayama, Yuji

    2016-06-02

    An increase in Src activity is commonly observed in epithelial cancers. Aberrant activation of the kinase activity is associated with malignant progression. However, the mechanisms that underlie the Src-induced malignant progression of cancer are not completely understood. We show here that v-Src, an oncogene that was first identified from a Rous sarcoma virus and a mutant variant of c-Src, leads to an increase in the number of anaphase and telophase cells having chromosome bridges. v-Src increases the number of γH2AX foci, and this increase is inhibited by treatment with PP2, a Src kinase inhibitor. v-Src induces the phosphorylation of KAP1 at Ser824, Chk2 at Thr68, and Chk1 at Ser345, suggesting the activation of the ATM/ATR pathway. Caffeine decreases the number of cells having chromosome bridges at a concentration incapable of inhibiting Chk1 phosphorylation at Ser345. These results suggest that v-Src induces chromosome bridges via generation of DNA damage and the subsequent DNA damage response, possibly by homologous recombination. A chromosome bridge gives rise to the accumulation of DNA damage directly through chromosome breakage and indirectly through cytokinesis failure-induced multinucleation. We propose that v-Src-induced chromosome bridge formation is one of the causes of the v-Src-induced malignant progression of cancer cells.

  2. Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage.

    PubMed

    Stork, Caroline Townsend; Bocek, Michael; Crossley, Madzia P; Sollier, Julie; Sanz, Lionel A; Chédin, Frédéric; Swigut, Tomek; Cimprich, Karlene A

    2016-08-23

    The hormone estrogen (E2) binds the estrogen receptor to promote transcription of E2-responsive genes in the breast and other tissues. E2 also has links to genomic instability, and elevated E2 levels are tied to breast cancer. Here, we show that E2 stimulation causes a rapid, global increase in the formation of R-loops, co-transcriptional RNA-DNA products, which in some instances have been linked to DNA damage. We show that E2-dependent R-loop formation and breast cancer rearrangements are highly enriched at E2-responsive genomic loci and that E2 induces DNA replication-dependent double-strand breaks (DSBs). Strikingly, many DSBs that accumulate in response to E2 are R-loop dependent. Thus, R-loops resulting from the E2 transcriptional response are a significant source of DNA damage. This work reveals a novel mechanism by which E2 stimulation leads to genomic instability and highlights how transcriptional programs play an important role in shaping the genomic landscape of DNA damage susceptibility.

  3. Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage

    PubMed Central

    Stork, Caroline Townsend; Bocek, Michael; Crossley, Madzia P; Sollier, Julie; Sanz, Lionel A; Chédin, Frédéric; Swigut, Tomek; Cimprich, Karlene A

    2016-01-01

    The hormone estrogen (E2) binds the estrogen receptor to promote transcription of E2-responsive genes in the breast and other tissues. E2 also has links to genomic instability, and elevated E2 levels are tied to breast cancer. Here, we show that E2 stimulation causes a rapid, global increase in the formation of R-loops, co-transcriptional RNA-DNA products, which in some instances have been linked to DNA damage. We show that E2-dependent R-loop formation and breast cancer rearrangements are highly enriched at E2-responsive genomic loci and that E2 induces DNA replication-dependent double-strand breaks (DSBs). Strikingly, many DSBs that accumulate in response to E2 are R-loop dependent. Thus, R-loops resulting from the E2 transcriptional response are a significant source of DNA damage. This work reveals a novel mechanism by which E2 stimulation leads to genomic instability and highlights how transcriptional programs play an important role in shaping the genomic landscape of DNA damage susceptibility. DOI: http://dx.doi.org/10.7554/eLife.17548.001 PMID:27552054

  4. Evaluation of oxidative stress and genetic damage caused by detergents in the zebrafish Danio rerio (Cyprinidae).

    PubMed

    Sobrino-Figueroa, Alma S

    2013-08-01

    Detergents are used in large quantities and some of their ingredients are highly toxic to aquatic organisms. In the present study the toxicity (lipid peroxidation) and genotoxic (frequency of DNA strand breaks) effects were evaluated in the gill and liver tissues of zebrafish (Danio rerio), exposed for 16days to a sublethal concentration (CL10) of two commercial detergents (laundry and dishwasher use) and an anionic surfactant: alkyl lauryl sulfonate (LAS). The results demonstrated high toxicity with dishwasher detergent, resulting in high lipid peroxidation levels (MDA malondialdehyde evaluation). No differences in MDA concentrations were found among fish exposed to laundry detergent and organisms exposed to LAS. In the genetic damage evaluation, significant differences in the number of cells with DNA strand breaks (comets) were observed: the fish exposed to dishwasher detergent presented the highest number of damaged cells (79%), in comparison with those exposed to other products (laundry and LAS) and the control group (8% damaged cells). The toxicity of dishwasher detergent (biological detergent containing enzymes and perfume) was higher than the value observed with LAS. Laundry detergent does not contain enzymes or perfume and its toxicity was similar to LAS. Since detergents are complex mixtures of different substances, in which additive and/or synergistic effects may occur, the deleterious effect caused by the dishwasher detergent was probably due to the combined effects of the ingredients of detergent.

  5. Causes and Consequences of Sensory Hair Cell Damage and Recovery in Fishes.

    PubMed

    Smith, Michael E; Monroe, J David

    2016-01-01

    Sensory hair cells are the mechanotransductive receptors that detect gravity, sound, and vibration in all vertebrates. Damage to these sensitive receptors often results in deficits in vestibular function and hearing. There are currently two main reasons for studying the process of hair cell loss in fishes. First, fishes, like other non-mammalian vertebrates, have the ability to regenerate hair cells that have been damaged or lost via exposure to ototoxic chemicals or acoustic overstimulation. Thus, they are used as a biomedical model to understand the process of hair cell death and regeneration and find therapeutics that treat or prevent human hearing loss. Secondly, scientists and governmental natural resource managers are concerned about the potential effects of intense anthropogenic sounds on aquatic organisms, including fishes. Dr. Arthur N. Popper and his students, postdocs and research associates have performed pioneering experiments in both of these lines of fish hearing research. This review will discuss the current knowledge regarding the causes and consequences of both lateral line and inner ear hair cell damage in teleost fishes.

  6. Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium) from Corals

    PubMed Central

    Fujise, Lisa; Yamashita, Hiroshi; Suzuki, Go; Sasaki, Kengo; Liao, Lawrence M.; Koike, Kazuhiko

    2014-01-01

    The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium). Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae) in aquaria under non-thermal stress (27°C) and moderate thermal stress conditions (30°C), and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress conditions corals actively expel a degraded form of Symbiodinium, which are thought to be digested by their host coral. This response was also observed at 30°C. However, while the expulsion rates of Symbiodinium cells remained constant, the proportion of degraded cells significantly increased at 30°C. This result indicates that corals more actively digest and expel damaged Symbiodinium under thermal stress conditions, likely as a mechanism for coping with environmental change. However, the increase in digested Symbiodinium expulsion under thermal stress may not fully keep up with accumulation of the damaged cells. There are more photosynthetically damaged Symbiodinium upon prolonged exposure to thermal stress, and corals release them without digestion to prevent their accumulation. This response may be an adaptive strategy to moderate stress to ensure survival, but the accumulation of damaged Symbiodinium, which causes subsequent coral deterioration, may occur when the response cannot cope with the magnitude or duration of environmental stress, and this might be a possible mechanism underlying coral bleaching during prolonged moderate thermal stress. PMID:25493938

  7. Oxidative DNA damage caused by pulsed discharge with cavitation on the bactericidal function

    NASA Astrophysics Data System (ADS)

    Kudo, Ken-ichi; Ito, Hironori; Ihara, Satoshi; Terato, Hiroaki

    2015-09-01

    Plasma-based techniques are expected to have practical use for wastewater purification with a potential for killing contaminated microorganisms and degrading recalcitrant materials. In the present study, we analysed oxidative DNA damage in bacterial cells treated by the plasma to unveil its mechanisms in the bactericidal process. Escherichia coli cell suspension was exposed to the plasma induced by applying an alternating-current voltage of about 1 kV with bubbling formed by water-cavitation, termed pulsed discharge with cavitation. Chromosomal DNA damage, such as double strand break (DSB) and oxidative base lesions, increased proportionally with the applied energy, as determined by electrophoretic and mass spectrometric analyses. Among the base lesions identified, the yields of 8-hydroxyguanine (8-OH-G) and 5-hydroxycytosine (5-OH-C) in chromosomal DNA increased by up to 4- and 15-fold, respectively, compared to untreated samples. The progeny DNA sequences, derived from plasmid DNA exposed to the plasma, indicated that the production rate of 5-OH-C exceeded that of 8-OH-G, as G:C to A:T transitions accounted for 65% of all base changes, but only a few G:C to T:A transversions were observed. The cell viabilities of E. coli cells decreased in direct proportion to increases in the applied energy. Therefore, the plasma-induced bactericidal mechanism appears to relate to oxidative damage caused to bacterial DNA. These results were confirmed by observing the generation of hydroxyl radicals and hydrogen peroxide molecules following the plasma exposure. We also compared our results with the plasma to those obtained with 137Cs γ-rays, as a well-known ROS generator to confirm the DNA-damaging mechanism involved.

  8. Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium) from Corals.

    PubMed

    Fujise, Lisa; Yamashita, Hiroshi; Suzuki, Go; Sasaki, Kengo; Liao, Lawrence M; Koike, Kazuhiko

    2014-01-01

    The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium). Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae) in aquaria under non-thermal stress (27°C) and moderate thermal stress conditions (30°C), and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress conditions corals actively expel a degraded form of Symbiodinium, which are thought to be digested by their host coral. This response was also observed at 30°C. However, while the expulsion rates of Symbiodinium cells remained constant, the proportion of degraded cells significantly increased at 30°C. This result indicates that corals more actively digest and expel damaged Symbiodinium under thermal stress conditions, likely as a mechanism for coping with environmental change. However, the increase in digested Symbiodinium expulsion under thermal stress may not fully keep up with accumulation of the damaged cells. There are more photosynthetically damaged Symbiodinium upon prolonged exposure to thermal stress, and corals release them without digestion to prevent their accumulation. This response may be an adaptive strategy to moderate stress to ensure survival, but the accumulation of damaged Symbiodinium, which causes subsequent coral deterioration, may occur when the response cannot cope with the magnitude or duration of environmental stress, and this might be a possible mechanism underlying coral bleaching during prolonged moderate thermal stress.

  9. Time-frequency vibration analysis for the detection of motor damages caused by bearing currents

    NASA Astrophysics Data System (ADS)

    Prudhom, Aurelien; Antonino-Daviu, Jose; Razik, Hubert; Climente-Alarcon, Vicente

    2017-02-01

    Motor failure due to bearing currents is an issue that has drawn an increasing industrial interest over recent years. Bearing currents usually appear in motors operated by variable frequency drives (VFD); these drives may lead to common voltage modes which cause currents induced in the motor shaft that are discharged through the bearings. The presence of these currents may lead to the motor bearing failure only few months after system startup. Vibration monitoring is one of the most common ways for detecting bearing damages caused by circulating currents; the evaluation of the amplitudes of well-known characteristic components in the vibration Fourier spectrum that are associated with race, ball or cage defects enables to evaluate the bearing condition and, hence, to identify an eventual damage due to bearing currents. However, the inherent constraints of the Fourier transform may complicate the detection of the progressive bearing degradation; for instance, in some cases, other frequency components may mask or be confused with bearing defect-related while, in other cases, the analysis may not be suitable due to the eventual non-stationary nature of the captured vibration signals. Moreover, the fact that this analysis implies to lose the time-dimension limits the amount of information obtained from this technique. This work proposes the use of time-frequency (T-F) transforms to analyse vibration data in motors affected by bearing currents. The experimental results obtained in real machines show that the vibration analysis via T-F tools may provide significant advantages for the detection of bearing current damages; among other, these techniques enable to visualise the progressive degradation of the bearing while providing an effective discrimination versus other components that are not related with the fault. Moreover, their application is valid regardless of the operation regime of the machine. Both factors confirm the robustness and reliability of these tools

  10. SMN deficiency in severe models of spinal muscular atrophy causes widespread intron retention and DNA damage.

    PubMed

    Jangi, Mohini; Fleet, Christina; Cullen, Patrick; Gupta, Shipra V; Mekhoubad, Shila; Chiao, Eric; Allaire, Norm; Bennett, C Frank; Rigo, Frank; Krainer, Adrian R; Hurt, Jessica A; Carulli, John P; Staropoli, John F

    2017-03-21

    Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease, is the leading monogenic cause of infant mortality. Homozygous loss of the gene survival of motor neuron 1 (SMN1) causes the selective degeneration of lower motor neurons and subsequent atrophy of proximal skeletal muscles. The SMN1 protein product, survival of motor neuron (SMN), is ubiquitously expressed and is a key factor in the assembly of the core splicing machinery. The molecular mechanisms by which disruption of the broad functions of SMN leads to neurodegeneration remain unclear. We used an antisense oligonucleotide (ASO)-based inducible mouse model of SMA to investigate the SMN-specific transcriptome changes associated with neurodegeneration. We found evidence of widespread intron retention, particularly of minor U12 introns, in the spinal cord of mice 30 d after SMA induction, which was then rescued by a therapeutic ASO. Intron retention was concomitant with a strong induction of the p53 pathway and DNA damage response, manifesting as γ-H2A.X positivity in neurons of the spinal cord and brain. Widespread intron retention and markers of the DNA damage response were also observed with SMN depletion in human SH-SY5Y neuroblastoma cells and human induced pluripotent stem cell-derived motor neurons. We also found that retained introns, high in GC content, served as substrates for the formation of transcriptional R-loops. We propose that defects in intron removal in SMA promote DNA damage in part through the formation of RNA:DNA hybrid structures, leading to motor neuron death.

  11. SMN deficiency in severe models of spinal muscular atrophy causes widespread intron retention and DNA damage

    PubMed Central

    Jangi, Mohini; Fleet, Christina; Cullen, Patrick; Gupta, Shipra V.; Mekhoubad, Shila; Chiao, Eric; Allaire, Norm; Bennett, C. Frank; Rigo, Frank; Krainer, Adrian R.; Hurt, Jessica A.; Carulli, John P.; Staropoli, John F.

    2017-01-01

    Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease, is the leading monogenic cause of infant mortality. Homozygous loss of the gene survival of motor neuron 1 (SMN1) causes the selective degeneration of lower motor neurons and subsequent atrophy of proximal skeletal muscles. The SMN1 protein product, survival of motor neuron (SMN), is ubiquitously expressed and is a key factor in the assembly of the core splicing machinery. The molecular mechanisms by which disruption of the broad functions of SMN leads to neurodegeneration remain unclear. We used an antisense oligonucleotide (ASO)-based inducible mouse model of SMA to investigate the SMN-specific transcriptome changes associated with neurodegeneration. We found evidence of widespread intron retention, particularly of minor U12 introns, in the spinal cord of mice 30 d after SMA induction, which was then rescued by a therapeutic ASO. Intron retention was concomitant with a strong induction of the p53 pathway and DNA damage response, manifesting as γ-H2A.X positivity in neurons of the spinal cord and brain. Widespread intron retention and markers of the DNA damage response were also observed with SMN depletion in human SH-SY5Y neuroblastoma cells and human induced pluripotent stem cell-derived motor neurons. We also found that retained introns, high in GC content, served as substrates for the formation of transcriptional R-loops. We propose that defects in intron removal in SMA promote DNA damage in part through the formation of RNA:DNA hybrid structures, leading to motor neuron death. PMID:28270613

  12. Methamphetamine causes mitrochondrial oxidative damage in human T lymphocytes leading to functional impairment.

    PubMed

    Potula, Raghava; Hawkins, Brian J; Cenna, Jonathan M; Fan, Shongshan; Dykstra, Holly; Ramirez, Servio H; Morsey, Brenda; Brodie, Michael R; Persidsky, Yuri

    2010-09-01

    Methamphetamine (METH) abuse is known to be associated with an inordinate rate of infections. Although many studies have described the association of METH exposure and immunosuppression, so far the underlying mechanism still remains elusive. In this study, we present evidence that METH exposure resulted in mitochondrial oxidative damage and caused dysfunction of primary human T cells. METH treatment of T lymphocytes led to a rise in intracellular calcium levels that enhanced the generation of reactive oxygen species. TCR-CD28 linked calcium mobilization and subsequent uptake by mitochondria in METH-treated T cells correlated with an increase in mitochondrion-derived superoxide. Exposure to METH-induced mitochondrial dysfunction in the form of marked decrease in mitochondrial membrane potential, increased mitochondrial mass, enhanced protein nitrosylation and diminished protein levels of complexes I, III, and IV of the electron transport chain. These changes paralleled reduced IL-2 secretion and T cell proliferative responses after TCR-CD28 stimulation indicating impaired T cell function. Furthermore, antioxidants attenuated METH-induced mitochondrial damage by preserving the protein levels of mitochondrial complexes I, III, and IV. Altogether, our data indicate that METH can cause T cell dysfunction via induction of oxidative stress and mitochondrial injury as underlying mechanism of immune impairment secondary to METH abuse.

  13. Managing crop damage caused by house mice (Mus domesticus) in Australia.

    PubMed

    Kaboodvandpour, Shahram; Leung, Luke K-P

    2010-03-01

    A large-scale outbreak of the house mouse populations occurs in grain growing in Australia on average once every four years. High densities of mice cause major yield losses to cereal crops, and low to moderate densities of mice also cause some losses. Several predictive models based on rainfall patterns have been developed to forecast mouse density. These models carry some uncertainty and the economic value of basing management actions on these models is not clear. Baiting is the most commonly used method and zinc phosphide and other rodenticide bait are effective in reducing up to 90% of mouse populations. Ecologically-based best farming practice for controlling mice has recently been developed on the basis of long-term field studies of mouse populations. No effective biological control method has been developed for mice. However, grain growers still cannot make economically rational decisions to implement control because they do not know the pest threshold density (D(T)) above which the economic benefits of control exceed the economic costs of control. Applied predator-prey theory suggests that understanding the relationship between mouse density and damage is the basis for determining D(T). Understanding this relationship is the first research priority for managing mouse damage. The other research priority is to develop a reliable method to estimate unbiased mouse density.

  14. Two-peptide bacteriocin PlnEF causes cell membrane damage to Lactobacillus plantarum.

    PubMed

    Zhang, Xu; Wang, Yang; Liu, Lei; Wei, Yunlu; Shang, Nan; Zhang, Xiangmei; Li, Pinglan

    2016-02-01

    Biologically active, artificially synthesized two-peptide bacteriocin PlnEF was used to study its mode of action on sensitive bacteria Lactobacillus plantarum pl2. The data obtained showed that PlnEF induced membrane permeabilization, allowing for the efflux of electrolytes, which was evidenced by the increased extracellular conductivity, the dissipation of transmembrane electrical potential and pH gradient, and rapid intracellular ATP depletion after L. plantarum pl2 cells were treated with PlnEF for minutes. Laser confocal microscopy showed that PlnEF accumulated very quickly in L. plantarum pl2 cells and the accumulation of PlnEF caused damage to cell membrane. Scanning electron microscopy and transmission electron microscopy further showed that PlnEF induced morphological changes and structure disruption to L. plantarum pl2 cells, such as the formation of blebs, microspheres, membrane deformation and cell lysis. In summary, the data obtained show that PlnEF caused cell membrane damage to L. plantarum pl2 cells. Our study reveals the antimicrobial mechanism of two-peptide bacteriocin PlnEF against L. plantarum.

  15. The innervation of the kidney in renal injury and inflammation: A cause and consequence of deranged cardiovascular control.

    PubMed

    Abdulla, Mohammed H; Johns, Edward J

    2017-02-09

    Extensive investigations have revealed that renal sympathetic nerves regulate renin secretion, tubular fluid reabsorption and renal haemodynamics which can impact on cardiovascular homoeostasis normally and in pathophysiological states. The significance of the renal afferent innervation and its role in determining the autonomic control of the cardiovascular system is uncertain. The transduction pathways at the renal afferent nerves have been shown to require pro-inflammatory mediators and TRPV1 channels. Reno-renal reflexes have been described, both inhibitory and excitatory, demonstrating that a neural link exists between kidneys and may determine the distribution of excretory and haemodynamic function between the two kidneys. The impact of renal afferent nerve activity on basal and reflex regulation of global sympathetic drive remains opaque. There is clinical and experimental evidence that in states of chronic kidney disease and renal injury there is infiltration of T-helper cells with a sympatho-excitation and blunting of the high and low pressure baroreceptor reflexes regulating renal sympathetic nerve activity. The baroreceptor deficits are renal nerve-dependent as the dysregulation can be relieved by renal denervation. There is also experimental evidence that in obese states there is a sympatho-excitation and disrupted baroreflex regulation of renal sympathetic nerve activity which is mediated by the renal innervation. This body of information provides an important basis for directing greater attention to the role of renal injury/inflammation causing an inappropriate activation of the renal afferent nerves as an important initiator of aberrant autonomic cardiovascular control. This article is protected by copyright. All rights reserved.

  16. What Happens After Treatment for Kidney Cancer?

    MedlinePlus

    ... Cancer After Treatment What Happens After Treatment for Kidney Cancer? For some people with kidney cancer, treatment can ... Treatment for Kidney Cancer Stops Working More In Kidney Cancer About Kidney Cancer Causes, Risk Factors, and Prevention ...

  17. Refractory hypotension and edema caused by right atrial compression in a woman with polycystic kidney disease.

    PubMed

    Lasic, Lada Beara; DeVita, Maria V; Spiegel, Paul J; Marino, Nino D; Mellow, Ellen; Michelis, Michael F

    2004-03-01

    We present the case of a 60-year-old woman with a history of autosomal dominant polycystic kidney disease and long-standing hypertension who developed persistent hypotension. While in the hospital for the treatment of bacteriemia, the patient had low systolic blood pressures (90 to 100 mm Hg), which was thought to be the consequence of infection. After the infection was adequately controlled and the blood pressure did not improve, an echocardiogram was done to further elucidate her hypotension. It was nondiagnostic and revealed an ejection fraction of 70% with left ventricular hypertrophy. Shortly after discharge, she developed significant lower extremity edema and her blood pressure remained low. Due to the low blood pressure it was not possible to mobilize the fluid with her dialysis treatments. A repeat transthoracic echocardiogram at that time revealed that the right atrium was partially compressed throughout the cardiac cycle by polycystic hepatic tissue. This tissue invaginated up through the right hemidiaphragm. A partial liver resection was considered for the patient. Instead, right nephrectomy was performed and the blood pressure improved.

  18. Cutaneous and renal glomerular vasculopathy as a cause of acute kidney injury in dogs in the UK

    PubMed Central

    Hawkins, I.; Robin, C.; Newton, R. J.; Jepson, R.; Stanzani, G.; McMahon, L. A.; Pesavento, P.; Carr, T.; Cogan, T.; Couto, C. G.; Cianciolo, R.; Walker, D. J.

    2015-01-01

    To describe the signalment, clinicopathological findings and outcome in dogs presenting with acute kidney injury (AKI) and skin lesions between November 2012 and March 2014, in whom cutaneous and renal glomerular vasculopathy (CRGV) was suspected and renal thrombotic microangiopathy (TMA) was histopathologically confirmed. The medical records of dogs with skin lesions and AKI, with histopathologically confirmed renal TMA, were retrospectively reviewed. Thirty dogs from across the UK were identified with clinicopathological findings compatible with CRGV. These findings included the following: skin lesions, predominantly affecting the distal extremities; AKI; and variably, anaemia, thrombocytopaenia and hyperbilirubinaemia. Known causes of AKI were excluded. The major renal histopathogical finding was TMA. All thirty dogs died or were euthanised. Shiga toxin was not identified in the kidneys of affected dogs. Escherichia coli genes encoding shiga toxin were not identified in faeces from affected dogs. CRGV has previously been reported in greyhounds in the USA, a greyhound in the UK, without renal involvement, and a Great Dane in Germany. This is the first report of a series of non-greyhound dogs with CRGV and AKI in the UK. CRGV is a disease of unknown aetiology carrying a poor prognosis when azotaemia develops. PMID:25802439

  19. Assessment of infrastructure functional damages caused by natural-technological disasters

    NASA Astrophysics Data System (ADS)

    Massabò, Marco; Trasforini, Eva; Traverso, Stefania; Rudari, Roberto; De Angeli, Silvia; Cecinati, Francesca; Cerruti, Valentina

    2013-04-01

    The assessment of infrastructure damages caused by technological disaster poses several challenges, from gathering needed information on the territorial system to the definition of functionality curves for infrastructures elements (such as, buildings, road school) that are exposed to both natural and technological event. Moreover, areas affected by natural or natech (technological disasters triggered by natural events) disasters have often very large extensions and a rapid survey of them to gather all the needed information is a very difficult task, for many reasons, not least the difficult access to the existing databases and resources. We use multispectral optical imagery with other geographical and unconventional data to identify and characterize exposed elements. Our efforts in the virtual survey and during the investigation steps have different aims: to identify the vulnerability of infrastructures, buildings or activities; to execute calculations of exposition to risk; to estimate physical and functional damages. Subsequently, we apply specific algorithms to estimate values of acting forces and physical and functional damages. The updated picture of target areas in terms of risk-prone people, infrastructures and their connections is very important. It is possible to develop algorithms providing values of systemic functionality for each network element. The methodology is here applied to a natech disaster, arising from the combination of a flood event (specifically, the January 2010 flooding of Drin and Buna rivers, with a worsening in the road safety levels in the Shkoder area) with and the subsequent overturning of a truck transporting hazardous material. The accident causes the loss of containment and the total material release. Once the release has taken place, the evolution will depend on the physical state of the substance spilled (liquid, gas or dust). As a specific case we consider the rupture of a trucks transporting liquid fuels such as gasoline

  20. 6-Gingerol-Rich Fraction from Zingiber officinale Prevents Hematotoxicity and Oxidative Damage in Kidney and Liver of Rats Exposed to Carbendazim.

    PubMed

    Salihu, Mariama; Ajayi, Babajide O; Adedara, Isaac A; Farombi, Ebenezer O

    2016-01-01

    Ginger (Zingiber officinale) is a globally marketed flavoring agent and cooking spice with a long history of human health benefits. The fungicide carbendazim (CBZ) is often detected in fruits and vegetables for human nutrition and has been reported to elicit toxic effects in different experimental animal models. The present study investigated the protective effects of 6-Gingerol-rich fraction (6-GRF) from ginger on hematotoxicity and hepatorenal damage in rats exposed to CBZ. CBZ was administered at a dose of 50 mg/kg alone or simultaneously administered with 6-GRF at 50, 100, and 200 mg/kg, whereas control rats received corn oil alone at 2 mL/kg for 14 days. Hematological examination showed that CBZ-mediated toxicity to the total white blood cell (WBC), neutrophils, lymphocytes, and platelets counts were normalized to the control values in rats cotreated with 6-GRF. Moreover, administration of CBZ significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase as well as glutathione level in the livers and kidneys of rats compared with control. However, the levels of hydrogen peroxide (H2O2) and malondialdehyde were markedly elevated in kidneys and livers of CBZ-treated rats compared with control. The significant elevation in the plasma indices of renal and hepatic dysfunction in CBZ-treated rats was confirmed by light microscopy. Coadministration of 6-GRF exhibited chemoprotection against CBZ-mediated hematotoxicity, augmented antioxidant status, and prevented oxidative damage in the kidney and liver of rats.

  1. Mild recessive mutations in six Fraser syndrome-related genes cause isolated congenital anomalies of the kidney and urinary tract.

    PubMed

    Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hilger, Alina C; Saisawat, Pawaree; Vivante, Asaf; Stajic, Natasa; Bogdanovic, Radovan; Reutter, Heiko M; Kehinde, Elijah O; Tasic, Velibor; Hildebrandt, Friedhelm

    2014-09-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) account for approximately 40% of children with ESRD in the United States. Hitherto, mutations in 23 genes have been described as causing autosomal dominant isolated CAKUT in humans. However, >90% of cases of isolated CAKUT still remain without a molecular diagnosis. Here, we hypothesized that genes mutated in recessive mouse models with the specific CAKUT phenotype of unilateral renal agenesis may also be mutated in humans with isolated CAKUT. We applied next-generation sequencing technology for targeted exon sequencing of 12 recessive murine candidate genes in 574 individuals with isolated CAKUT from 590 families. In 15 of 590 families, we identified recessive mutations in the genes FRAS1, FREM2, GRIP1, FREM1, ITGA8, and GREM1, all of which function in the interaction of the ureteric bud and the metanephric mesenchyme. We show that isolated CAKUT may be caused partially by mutations in recessive genes. Our results also indicate that biallelic missense mutations in the Fraser/MOTA/BNAR spectrum genes cause isolated CAKUT, whereas truncating mutations are found in the multiorgan form of Fraser syndrome. The newly identified recessive biallelic mutations in these six genes represent the molecular cause of isolated CAKUT in 2.5% of the 590 affected families in this study.

  2. The damage to a person caused by venous thromboembolism in the civil responsibility.

    PubMed

    Di Blasi, A; Di Blasi, L; Manferoce, O; Napoli, P

    2000-01-01

    The venous thromboembolism can clinically show itself as deep venous thrombosis or as pulmonary embolism. Both serious and potentially fatal, for this high incidence, they assume importance in social economic sphere. The authors take into account the medicolegal diagnostics methodology of the deep venous thrombosis and of the pulmonary embolism, the traumatic and post traumatic etiology, to determine the connection of causality and the estimating parameters of the damage to a person in the sphere of civil responsibility. To attain to a certain diagnosis of thromboembolism, since its difficult cause of paucisymtomaticity or asymtomaticity of the pathology after an attentive evaluation of symptoms, clinic manifestations and factors of risk, it can't be disregarded to utilize scientific diagnostic criteria, and instrumental ascertainments, serial too, helped by conventional means of standardization, such as the new American system of classification CEAP. The following phases of medicolegal ascertainment consist in identifying the causal connection between disease and event and in estimating of the damage to a person, with rigorous and objective methodology and using tabular orientation guides, that have to indicate the percentage incidence of the undergone disablement on the person's validity for indemnity. It is showed the particular delicacy of the medical examiner's evaluation in thromboembolic disease, in the sphere of civil responsibility, both for the difficulties of the diagnostic identification of the deep venous thrombosis, and of the pulmonary embolism, and for the determination of the connection of causality with traumatic events and with following operation of orthopedics-traumatology and neurosurgery (sector on which the most difficult problems of professional responsibility can connect) and finally for the real evaluation of the consequent damage to a persons, in order to its indemnity.

  3. Loss of p21 Permits Carcinogenesis from Chronically Damaged Liver and Kidney Epithelial Cells Despite Unchecked Apoptosis

    PubMed Central

    Willenbring, Holger; Sharma, Amar Deep; Vogel, Arndt; Lee, Andrew Young; Rothfuss, Andreas; Wang, Zhongya; Finegold, Milton; Grompe, Markus

    2008-01-01

    SUMMARY Accumulation of toxic metabolites in tyrosinemia type I (HT1) patients leads to chronic DNA damage and the highest risk for hepatocellular carcinomas (HCCs) of any human disease. Here we show that hepatocytes of HT1 mice exhibit a profound cell cycle arrest which, despite concomitant apoptosis resistance, causes mortality from impaired liver regeneration. However, additional loss of p21 in HT1 mice restores the proliferative capabilities of hepatocytes and renal proximal tubular cells. This growth response compensates cell loss due to uninhibited apoptosis and enables animal survival but rapidly leads to HCCs, renal cysts and renal carcinomas. Thus, p21’s antiproliferative function is indispensable for the suppression of carcinogenesis from chronically injured liver and renal epithelial cells and cannot be compensated by apoptosis. PMID:18598944

  4. Repair of clustered DNA damage caused by high LET radiation in human fibroblasts

    NASA Technical Reports Server (NTRS)

    Rydberg, B.; Lobrich, M.; Cooper, P. K.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    It has recently been demonstrated experimentally that DNA damage induced by high LET radiation in mammalian cells is non-randomly distributed along the DNA molecule in the form of clusters of various sizes. The sizes of such clusters range from a few base-pairs to at least 200 kilobase-pairs. The high biological efficiency of high LET radiation for induction of relevant biological endpoints is probably a consequence of this clustering, although the exact mechanisms by which the clustering affects the biological outcome is not known. We discuss here results for induction and repair of base damage, single-strand breaks and double-strand breaks for low and high LET radiations. These results are discussed in the context of clustering. Of particular interest is to determine how clustering at different scales affects overall rejoining and fidelity of rejoining of DNA double-strand breaks. However, existing methods for measuring repair of DNA strand breaks are unable to resolve breaks that are close together in a cluster. This causes problems in interpretation of current results from high LET radiation and will require new methods to be developed.

  5. Importance of cell damage causing growth delay for high pressure inactivation of Saccharomyces cerevisiae

    NASA Astrophysics Data System (ADS)

    Nanba, Masaru; Nomura, Kazuki; Nasuhara, Yusuke; Hayashi, Manabu; Kido, Miyuki; Hayashi, Mayumi; Iguchi, Akinori; Shigematsu, Toru; Hirayama, Masao; Ueno, Shigeaki; Fujii, Tomoyuki

    2013-06-01

    A high pressure (HP) tolerant (barotolerant) mutant a2568D8 and a variably barotolerant mutant a1210H12 were generated from Saccharomyces cerevisiae using ultra-violet mutagenesis. The two mutants, a barosensitive mutant a924E1 and the wild-type strain, were pressurized (225 MPa), and pressure inactivation behavior was analyzed. In the wild-type strain, a proportion of the growth-delayed cells were detected after exposure to HP. In a924E1, the proportion of growth-delayed cells significantly decreased compared with the wild-type. In a2568D8, the proportion of growth-delayed cells increased and the proportion of inactivated cells decreased compared with the wild-type. In a1210H12, the growth-delayed cells could not be detected within 120 s of exposure to HP. The proportion of growth-delayed cells, which incurred the damage, would affect the survival ratio by HP. These results suggested that cellular changes in barotolerance caused by mutations are remarkably affected by the ability to recover from cellular damage, which results in a growth delay.

  6. Three variables are better than one: detection of european winter windstorms causing important damages

    NASA Astrophysics Data System (ADS)

    Deroche, M.-S.; Choux, M.; Codron, F.; Yiou, P.

    2014-04-01

    In this paper, we present a new approach for detecting potentially damaging European winter windstorms from a multi-variable perspective. European winter windstorms being usually associated with extra-tropical cyclones (ETCs), there is a coupling between the intensity of the surface wind speeds and other meso-scale and large-scale features characteristic of ETCs. Here we focus on the relative vorticity at 850 hPa and the sea level pressure anomaly, which are also used in ETC detection studies, along with the ratio of the 10 m wind speed to its 98th percentile. When analysing 10 events known by the insurance industry to have caused extreme damages, we find that they share an intense signature in each of the 3 fields. This shows that the relative vorticity and the mean sea level pressure have a predictive value of the intensity of the generated windstorms. The 10 major events are not the most intense in any of the 3 variables considered separately, but we show that the combination of the 3 variables is an efficient way of extracting these events from a reanalysis data set.

  7. Assessment of concrete damage and strength degradation caused by reinforcement corrosion

    NASA Astrophysics Data System (ADS)

    Nepal, Jaya; Chen, Hua-Peng

    2015-07-01

    Structural performance deterioration of reinforced concrete structures has been extensively investigated, but very limited studies have been carried out to investigate the effect of reinforcement corrosion on time-dependent reliability with consideration of the influence of mechanical characteristics of the bond interface due to corrosion. This paper deals with how corrosion in reinforcement creates different types of defects in concrete structure and how they are responsible for the structural capacity deterioration of corrosion affected reinforced concrete structures during their service life. Cracking in cover concrete due to reinforcement corrosion is investigated by using rebar-concrete model and realistic concrete properties. The flexural strength deterioration is analytically predicted on the basis of bond strength evolution due to reinforcement corrosion, which is examined by the experimental data available. The time-dependent reliability analysis is undertaken to calculate the life time structural reliability of corrosion damaged concrete structures by stochastic deterioration modelling of reinforced concrete. The results from the numerical example show that the proposed approach is capable of evaluating the damage caused by reinforcement corrosion and also predicting the structural reliability of concrete structures during their lifecycle.

  8. A Rare Cause of Acute Kidney Injury in a Female Patient with Breast Cancer Presenting as Renal Colic

    PubMed Central

    2016-01-01

    Renal infarction is a rare cause of acute kidney injury which could lead to permanent loss of renal function. A prompt diagnosis is necessary in order to achieve a successful revascularization of the occluded artery. Given the rarity of the disease and the paucity of the reported cases in the previous literature a high index of suspicion must be maintained not only in the classical cardiac sources of systemic emboli (atrial fibrillation, dilated cardiomyopathy, or endocarditis), but also in the situations when a hypercoagulable state is presumed. The unspecific presenting symptoms often mask the true etiology of the patient's complaints. We present here a rare case of renal infarction that occurred in the setting of a hypercoagulable state, in a female patient with a history of breast cancer and documented hepatic metastases. PMID:27293927

  9. Monitoring of Maize Damage Caused by Western Corn Rootworm by Remote Sensing

    NASA Astrophysics Data System (ADS)

    Nádor, G.; Fényes, D.; Vasas, L.; Surek, G.

    2009-04-01

    The gradual dispersion of western corn rootworm (WCR) is becoming a serious maize pest in Europe, and all over the world. In 2008 using remote sensing data, the Remote Sensing Centre of Institute of Geodesy, Cartography and Remote Sensing (FÖMI RSC) carried out this project to identify WCR larval damage. Our goal with the present project is to assess and identify the disorder and structural changes caused by WCR larvae using optical (IRS-P6 AWiFS, IRS-P6 LISS, SPOT4 and SPOT5) and polarimetic radar (ALOS PALSAR) satellite images. We used 3 different individual features (Mono-maize feature, Optical feature, Radar feature) derived from remote sensing data to accomplish this goal. Findings were tested against on-the-spot ground assessments. Using radar polarimetry increased the accuracy significantly. The final results have implications for plant protection strategy, farming practices, pesticide producers, state authorities and research institutes.

  10. Estrogen inhibits tuberoinfundibular dopaminergic neurons but does not cause irreversible damage.

    PubMed

    Morel, Gustavo R; Carón, Rubén W; Cónsole, Gloria M; Soaje, Marta; Sosa, Yolanda E; Rodríguez, Silvia S; Jahn, Graciela A; Goya, Rodolfo G

    2009-12-16

    Dopaminergic neurons of the hypothalamic tuberoinfundibular dopaminergic (TIDA) system exert a tonic inhibitory control on prolactin (PRL) secretion whereas estrogen, known to inhibit TIDA neuron function, has been postulated to be toxic to TIDA neurons when it is chronically high. In order to determine whether estrogen in high doses can cause permanent damage to TIDA function, we submitted young female rats to continue high doses of estrogen administered, either centrally (intrahypothalamic estrogen implants) or peripherally (subcutaneous estrogen implants or weekly intramuscular (i.m.) injections for 7 weeks), subsequently withdrawing the steroid and observing the evolution of lactotrophes, serum PRL and TIDA neurons. Serum PRL was measured by radioimmunoassay whereas tyrosine hydroxylase positive (TH+) neurons and PRL cells were morphometrically assessed in sections of fixed hypothalami and pituitaries, respectively. After 30 days, hypothalamic estrogen implants induced a significant increase in serum PRL, whereas TH+ neurons were not detectable in the arcuate-periventricular hypothalamic (ARC) region of estrogen-implanted rats. Removal of implants on day 30 restored TH expression in the ARC and brought serum PRL back to basal levels 30 days after estrogen withdrawal. Subcutaneous or i.m. administration of estrogen for 7 weeks induced a marked hyperprolactinemia. However, 30 weeks after estrogen withdrawal, TH neuron numbers in the ARC were back to normal and serum PRL returned to basal levels. After peripheral but not central estrogen withdrawal, pituitary weight and lactotrophic cell numbers remained slightly increased. Our data suggest that estrogen even at high doses, does not cause permanent damage to TIDA neurons.

  11. Mutations of the Thyroid Hormone Transporter MCT8 Cause Prenatal Brain Damage and Persistent Hypomyelination

    PubMed Central

    López-Espíndola, Daniela; Morales-Bastos, Carmen; Grijota-Martínez, Carmen; Liao, Xiao-Hui; Lev, Dorit; Sugo, Ella; Verge, Charles F.; Refetoff, Samuel

    2014-01-01

    Context: Mutations in the MCT8 (SLC16A2) gene, encoding a specific thyroid hormone transporter, cause an X-linked disease with profound psychomotor retardation, neurological impairment, and abnormal serum thyroid hormone levels. The nature of the central nervous system damage is unknown. Objective: The objective of the study was to define the neuropathology of the syndrome by analyzing brain tissue sections from MCT8-deficient subjects. Design: We analyzed brain sections from a 30th gestational week male fetus and an 11-year-old boy and as controls, brain tissue from a 30th and 28th gestational week male and female fetuses, respectively, and a 10-year-old girl and a 12-year-old boy. Methods: Staining with hematoxylin-eosin and immunostaining for myelin basic protein, 70-kDa neurofilament, parvalbumin, calbindin-D28k, and synaptophysin were performed. Thyroid hormone determinations and quantitative PCR for deiodinases were also performed. Results: The MCT8-deficient fetus showed a delay in cortical and cerebellar development and myelination, loss of parvalbumin expression, abnormal calbindin-D28k content, impaired axonal maturation, and diminished biochemical differentiation of Purkinje cells. The 11-year-old boy showed altered cerebellar structure, deficient myelination, deficient synaptophysin and parvalbumin expression, and abnormal calbindin-D28k expression. The MCT8-deficient fetal cerebral cortex showed 50% reduction of thyroid hormones and increased type 2 deiodinase and decreased type 3 deiodinase mRNAs. Conclusions: The following conclusions were reached: 1) brain damage in MCT8 deficiency is diffuse, without evidence of focal lesions, and present from fetal stages despite apparent normality at birth; 2) deficient hypomyelination persists up to 11 years of age; and 3) the findings are compatible with the deficient action of thyroid hormones in the developing brain caused by impaired transport to the target neural cells. PMID:25222753

  12. Calcium citrate without aluminum antacids does not cause aluminum retention in patients with functioning kidneys

    NASA Technical Reports Server (NTRS)

    Sakhaee, K.; Wabner, C. L.; Zerwekh, J. E.; Copley, J. B.; Pak, L.; Poindexter, J. R.; Pak, C. Y.

    1993-01-01

    It has been suggested that calcium citrate might enhance aluminum absorption from food, posing a threat of aluminum toxicity even in patients with normal renal function. We therefore measured serum and urinary aluminum before and following calcium citrate therapy in patients with moderate renal failure and in normal subjects maintained on constant metabolic diets with known aluminum content (967-1034 mumol/day, or 26.1-27.9 mg/day, in patients and either 834 or 1579 mumol/day, or 22.5 and 42.6 mg/day, in normal subjects). Seven patients with moderate renal failure (endogenous creatinine clearance of 43 ml/min) took 50 mmol (2 g) calcium/day as effervescent calcium citrate with meals for 17 days. Eight normal women received 25 mmol (1 g) calcium/day as tricalcium dicitrate tablets with meals for 7 days. In patients with moderate renal failure, serum and urinary aluminum were normal before treatment at 489 +/- 293 SD nmol/l (13.2 +/- 7.9 micrograms/l) and 767 +/- 497 nmol/day (20.7 +/- 13.4 micrograms/day), respectively. They remained within normal limits and did not change significantly during calcium citrate treatment (400 +/- 148 nmol/l and 600 +/- 441 nmol/day, respectively). Similarly, no significant change in serum and urinary aluminum was detected in normal women during calcium citrate administration (271 +/- 59 vs 293 +/- 85 nmol/l and 515 +/- 138 vs 615 +/- 170 nmol/day, respectively). In addition, skeletal bone aluminum content did not change significantly in 14 osteoporotic patients (endogenous creatinine clearance of 68.5 ml/min) treated for 24 months with calcium citrate, 10 mmol calcium twice/day separately from meals (29.3 +/- 13.9 ng/mg ash bone to 27.9 +/0- 10.4, P = 0.727). In them, histomorphometric examination did not show any evidence of mineralization defect. Thus, calcium citrate given alone without aluminum-containing drugs does not pose a risk of aluminum toxicity in subjects with normal or functioning kidneys, when it is administered on an

  13. 99mTc-labeled HYNIC-DAPI causes plasmid DNA damage with high efficiency.

    PubMed

    Kotzerke, Joerg; Punzet, Robert; Runge, Roswitha; Ferl, Sandra; Oehme, Liane; Wunderlich, Gerd; Freudenberg, Robert

    2014-01-01

    (99m)Tc is the standard radionuclide used for nuclear medicine imaging. In addition to gamma irradiation, (99m)Tc emits low-energy Auger and conversion electrons that deposit their energy within nanometers of the decay site. To study the potential for DNA damage, direct DNA binding is required. Plasmid DNA enables the investigation of the unprotected interactions between molecules and DNA that result in single-strand breaks (SSBs) or double-strand breaks (DSBs); the resulting DNA fragments can be separated by gel electrophoresis and quantified by fluorescent staining. This study aimed to compare the plasmid DNA damage potential of a (99m)Tc-labeled HYNIC-DAPI compound with that of (99m)Tc pertechnetate ((99m)TcO4(-)). pUC19 plasmid DNA was irradiated for 2 or 24 hours. Direct and radical-induced DNA damage were evaluated in the presence or absence of the radical scavenger DMSO. For both compounds, an increase in applied activity enhanced plasmid DNA damage, which was evidenced by an increase in the open circular and linear DNA fractions and a reduction in the supercoiled DNA fraction. The number of SSBs elicited by 99mTc-HYNIC-DAPI (1.03) was twice that caused by (99m)TcO4(-) (0.51), and the number of DSBs increased fivefold in the (99m)Tc-HYNIC-DAPI-treated sample compared with the (99m)TcO4(-) treated sample (0.02 to 0.10). In the presence of DMSO, the numbers of SSBs and DSBs decreased to 0.03 and 0.00, respectively, in the (99m)TcO4(-) treated samples, whereas the numbers of SSBs and DSBs were slightly reduced to 0.95 and 0.06, respectively, in the (99m)Tc-HYNIC-DAPI-treated samples. These results indicated that (99m)Tc-HYNIC-DAPI induced SSBs and DSBs via a direct interaction of the (99m)Tc-labeled compound with DNA. In contrast to these results, (99m)TcO4(-) induced SSBs via radical formation, and DSBs were formed by two nearby SSBs. The biological effectiveness of (99m)Tc-HYNIC-DAPI increased by approximately 4-fold in terms of inducing SSBs and by

  14. 99mTc-Labeled HYNIC-DAPI Causes Plasmid DNA Damage with High Efficiency

    PubMed Central

    Kotzerke, Joerg; Punzet, Robert; Runge, Roswitha; Ferl, Sandra; Oehme, Liane; Wunderlich, Gerd; Freudenberg, Robert

    2014-01-01

    99mTc is the standard radionuclide used for nuclear medicine imaging. In addition to gamma irradiation, 99mTc emits low-energy Auger and conversion electrons that deposit their energy within nanometers of the decay site. To study the potential for DNA damage, direct DNA binding is required. Plasmid DNA enables the investigation of the unprotected interactions between molecules and DNA that result in single-strand breaks (SSBs) or double-strand breaks (DSBs); the resulting DNA fragments can be separated by gel electrophoresis and quantified by fluorescent staining. This study aimed to compare the plasmid DNA damage potential of a 99mTc-labeled HYNIC-DAPI compound with that of 99mTc pertechnetate (99mTcO4−). pUC19 plasmid DNA was irradiated for 2 or 24 hours. Direct and radical-induced DNA damage were evaluated in the presence or absence of the radical scavenger DMSO. For both compounds, an increase in applied activity enhanced plasmid DNA damage, which was evidenced by an increase in the open circular and linear DNA fractions and a reduction in the supercoiled DNA fraction. The number of SSBs elicited by 99mTc-HYNIC-DAPI (1.03) was twice that caused by 99mTcO4− (0.51), and the number of DSBs increased fivefold in the 99mTc-HYNIC-DAPI-treated sample compared with the 99mTcO4− treated sample (0.02 to 0.10). In the presence of DMSO, the numbers of SSBs and DSBs decreased to 0.03 and 0.00, respectively, in the 99mTcO4– treated samples, whereas the numbers of SSBs and DSBs were slightly reduced to 0.95 and 0.06, respectively, in the 99mTc-HYNIC-DAPI-treated samples. These results indicated that 99mTc-HYNIC-DAPI induced SSBs and DSBs via a direct interaction of the 99mTc-labeled compound with DNA. In contrast to these results, 99mTcO4− induced SSBs via radical formation, and DSBs were formed by two nearby SSBs. The biological effectiveness of 99mTc-HYNIC-DAPI increased by approximately 4-fold in terms of inducing SSBs and by approximately 10-fold in terms of

  15. Maize Purple Plant Pigment Protects Against Fluoride-Induced Oxidative Damage of Liver and Kidney in Rats

    PubMed Central

    Zhang, Zhuo; Zhou, Bo; Wang, Hiaohong; Wang, Fei; Song, Yingli; Liu, Shengnan; Xi, Shuhua

    2014-01-01

    Anthocyanins are polyphenols and well known for their biological antioxidative benefits. Maize purple plant pigment (MPPP) extracted and separated from maize purple plant is rich in anthocyanins. In the present study, MPPP was used to alleviate the adverse effects generated by fluoride on liver and kidney in rats. The results showed that the ultrastructure of the liver and kidney in fluoride treated rats displayed shrinkage of nuclear and cell volume, swollen mitochondria and endoplasmic reticulum and vacuols formation in the liver and kidney cells. MPPP significantly attenuated these fluoride-induced pathological changes. The MDA levels in serum and liver tissue of fluoride alone treated group were significantly higher than those of the control group (p < 0.05). The presence of 5 g/kg MPPP in the diet reduced the elevation of MDA levels in blood and liver, and increased the SOD and GSH-Px activities in kidney and GSH level in liver and kidney compared with the fluoride alone treated group (p < 0.05). In addition, MPPP alleviated the decrease of Bcl-2 protein expression and the increase of Bax protein expression induced by fluoride. This study demonstrated the protective role of MPPP against fluoride-induced oxidative stress in liver and kidney of rats. PMID:24419046

  16. Reactive oxygen species cause direct damage of Engelbreth-Holm-Swarm matrix.

    PubMed Central

    Riedle, B.; Kerjaschki, D.

    1997-01-01

    -linking bityrosine groups. ROS scavengers pinpointed to the hydroxyl radical as the most damaging radical species. Protease inhibitor experiments suggested that degradation of matrix proteins was caused primarily by the direct action of ROS and not by proteolysis by potentially contaminating proteases. Collectively, these results provide evidence that EHS matrix proteins show differential sensitivity to ROS-induced damage in a reproducible, sequential pattern, in the order entactin > laminin > type IV collagen, and that ROS cause partial dissociation and cross-linking of the EHS matrix. Images Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 11 PMID:9212747

  17. The Carrier's Liability for Damage Caused by Delay in International Air Transport

    NASA Technical Reports Server (NTRS)

    Lee, Kang Bin

    2003-01-01

    Delay in the air transport occurs when passengers, baggage or cargo do not arrive at their destination at the time indicated in the contract of carriage. The causes of delay in the carriage of passengers are booking errors or double booking, delayed departure of aircraft, incorrect information regarding the time of departure, failure to land at the scheduled destination and changes in flight schedule or addition of extra landing stops. Delay in the carriage of baggage or cargo may have different causes: no reservation, lack of space, failure to load the baggage or cargo at the right place, or to deliver the covering documents at the right place. The Montreal Convention of 1999 Article 19 provides that 'The carrier is liable for damage occasioned by delay in the carriage by air of passengers, baggage or cargo. Nevertheless, the carder shall not be liable for damage occasioned by delay if it proves that it and its servants and agents took all measures that could reasonably be required to avoid the damage or that it was impossible for it or them to take such measures'. The Montreal Convention Article 22 provides liability limits of the carrier in case of delay for passengers and their baggage and for cargo. In the carriage of persons, the liability of the carrier for each passenger is limited to 4,150 SDR. In the carriage of baggage, the liability of the carrier is limited to 1,000 SDR for each passenger unless a special declaration as to the value of the baggage has been made. In the carriage of cargo, the liability of the carrier is limited to 17 SDR per kilogram unless a special declaration as to the value of the cargo has been made. The Montreal Convention Article 19 has shortcomings: it is silent on the duration of the liability for carriage,andit does not make any distinction between persons and good. It does not give any indication concerning the circumstances to be taken into account in cases of delay, and about the length of delay. In conclusion, it is

  18. Murine liver damage caused by exposure to nano-titanium dioxide

    NASA Astrophysics Data System (ADS)

    Hong, Jie; Zhang, Yu-Qing

    2016-03-01

    Due to its unique physiochemical properties, nano-titanium dioxide (nano-TiO2) is widely used in all aspects of people’s daily lives, bringing it into increasing contact with humans. Thus, this material’s security issues for humans have become a heavily researched subject. Nano-TiO2 can enter the body through the mouth, skin, respiratory tract or in other ways, after which it enters the blood circulation and is deposited in the liver, changing biochemical indicators and causing liver inflammation. Meanwhile, the light sensitivity of these nanoparticles allows them to become media-generating reactive oxygen species (ROS), causing an imbalance between oxidation and anti-oxidation that leads to oxidative stress and liver damage. Nano-TiO2 can be transported into cells via phagocytosis, where the nanoparticles bind to the mitochondrial membrane, resulting in the disintegration of the membrane and the electron transport chain within the mitochondria. Thus, more ROS are produced. Nano-TiO2 can also enter the nucleus, where it can directly embed into or indirectly affect DNA, thereby causing DNA breakage or affecting gene expression. These effects include increased mRNA and protein expression levels of inflammation-related factors and decreased mRNA and protein expression levels of IκB and IL-2, resulting in inflammation. Long-term inflammation of the liver causes HSC cell activation, and extracellular matrix (ECM) deposition is promoted by multiple signalling pathways, resulting in liver fibrosis. In this paper, the latest progress on murine liver injury induced by environmental TiO2 is systematically described. The toxicity of nano-TiO2 also depends on size, exposure time, surface properties, dosage, administration route, and its surface modification. Therefore, its toxic effects in humans should be studied in greater depth. This paper also provides useful reference information regarding the safe use of nano-TiO2 in the future.

  19. Protective effects of curcumin against oxidative stress parameters and DNA damage in the livers and kidneys of rats with biliary obstruction.

    PubMed

    Tokaç, Mehmet; Taner, Gökçe; Aydın, Sevtap; Ozkardeş, Alper Bilal; Dündar, Halit Ziya; Taşlıpınar, Mine Yavuz; Arıkök, Ata Türker; Kılıç, Mehmet; Başaran, Arif Ahmet; Basaran, Nursen

    2013-11-01

    Curcumin, a most active antioxidant compound, has been suggested to have potential beneficial effects against most metabolic and psychological disorders, including cholestasis. In the present study, the effects of curcumin against oxidative stress and DNA damage induced by bile duct ligation (BDL) in Wistar albino rats for 14 days were investigated. The rats were divided into three following groups: Sham group, the BDL group and the BDL+curcumin group. A daily dose of 50mg/kg curcumin was given to the BDL+curcumin group intragastrically for 14 days. The biomarkers of hepatocellular damage were decreased in the BDL+curcumin group compared to the BDL group, indicating that curcumin recovered the liver functions. DNA damage as assessed by the alkaline comet assay was also found to be low in the BDL+curcumin group. Curcumin significantly reduced malondialdehyde and nitric oxide levels, and enchanced reduced glutathione levels and catalase, superoxide dismutase, and glutathione S-transferase enzymes activities in the livers and kidneys of BDL group. Curcumin treatment in BDL group was found to decrease tumor necrosis factor-alpha levels in the livers of rats. These results suggest that curcumin might have protective effects on the cholestasis-induced injuries in the liver and kidney tissues of rats.

  20. Mitochondrion-mediated apoptosis is involved in reproductive damage caused by BPA in male rats.

    PubMed

    Wang, Peng; Luo, Chunhua; Li, Qianyuan; Chen, Sai; Hu, Yong

    2014-11-01

    Bisphenol A (BPA) is a widely used environmental endocrine disruptor. Many studies have reported that BPA exposure shows reproductive toxicity and causes apoptosis in spermatogenic cells. However, few studies have investigated the relationship between the mitochondrial pathway and BPA-induced apoptosis. This study investigated the role of the mitochondrial pathway in apoptosis induced by BPA, which resulted in compromised male rat spermatogenesis and reproductive damage. Rats were exposed to various BPA concentrations (0, 50, 100, or 200mg of BPA/kg body weight per day), and factors in the mitochondrial signal transduction pathway and the apoptosis indices of spermatogenic cells were measured and sperm characteristics were analyzed. Our data revealed that BPA exposure increased the protein and mRNA levels of cytochrome C, apoptosis-inducing factor, caspase-3/9, and Bax; caspase-3 and caspase-9 activities; and the apoptosis indices of spermatogenic cells. In addition, abnormal structure of mitochondria and decreased protein and gene levels of Bcl-2 were observed following BPA exposure. These results suggest that apoptosis in the mitochondrial pathway mediates compromised reproductive system function caused by BPA exposure.

  1. 76 FR 54531 - Pipeline Safety: Potential for Damage to Pipeline Facilities Caused by the Passage of Hurricanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... Facilities Caused by the Passage of Hurricanes AGENCY: Pipeline and Hazardous Materials Safety Administration... to pipeline facilities caused by the passage of Hurricanes. ADDRESSES: This document can be viewed on...-related issues that can result from the passage of hurricanes. That includes the potential for damage...

  2. ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects

    PubMed Central

    Qiu, Haiyan; Lee, Sebum; Shang, Yulei; Wang, Wen-Yuan; Au, Kin Fai; Kamiya, Sherry; Barmada, Sami J.; Finkbeiner, Steven; Lui, Hansen; Carlton, Caitlin E.; Tang, Amy A.; Oldham, Michael C.; Wang, Hejia; Shorter, James; Filiano, Anthony J.; Roberson, Erik D.; Tourtellotte, Warren G.; Chen, Bin; Tsai, Li-Huei; Huang, Eric J.

    2014-01-01

    Autosomal dominant mutations of the RNA/DNA binding protein FUS are linked to familial amyotrophic lateral sclerosis (FALS); however, it is not clear how FUS mutations cause neurodegeneration. Using transgenic mice expressing a common FALS-associated FUS mutation (FUS-R521C mice), we found that mutant FUS proteins formed a stable complex with WT FUS proteins and interfered with the normal interactions between FUS and histone deacetylase 1 (HDAC1). Consequently, FUS-R521C mice exhibited evidence of DNA damage as well as profound dendritic and synaptic phenotypes in brain and spinal cord. To provide insights into these defects, we screened neural genes for nucleotide oxidation and identified brain-derived neurotrophic factor (Bdnf) as a target of FUS-R521C–associated DNA damage and RNA splicing defects in mice. Compared with WT FUS, mutant FUS-R521C proteins formed a more stable complex with Bdnf RNA in electrophoretic mobility shift assays. Stabilization of the FUS/Bdnf RNA complex contributed to Bdnf splicing defects and impaired BDNF signaling through receptor TrkB. Exogenous BDNF only partially restored dendrite phenotype in FUS-R521C neurons, suggesting that BDNF-independent mechanisms may contribute to the defects in these neurons. Indeed, RNA-seq analyses of FUS-R521C spinal cords revealed additional transcription and splicing defects in genes that regulate dendritic growth and synaptic functions. Together, our results provide insight into how gain-of-function FUS mutations affect critical neuronal functions. PMID:24509083

  3. ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects.

    PubMed

    Qiu, Haiyan; Lee, Sebum; Shang, Yulei; Wang, Wen-Yuan; Au, Kin Fai; Kamiya, Sherry; Barmada, Sami J; Finkbeiner, Steven; Lui, Hansen; Carlton, Caitlin E; Tang, Amy A; Oldham, Michael C; Wang, Hejia; Shorter, James; Filiano, Anthony J; Roberson, Erik D; Tourtellotte, Warren G; Chen, Bin; Tsai, Li-Huei; Huang, Eric J

    2014-03-01

    Autosomal dominant mutations of the RNA/DNA binding protein FUS are linked to familial amyotrophic lateral sclerosis (FALS); however, it is not clear how FUS mutations cause neurodegeneration. Using transgenic mice expressing a common FALS-associated FUS mutation (FUS-R521C mice), we found that mutant FUS proteins formed a stable complex with WT FUS proteins and interfered with the normal interactions between FUS and histone deacetylase 1 (HDAC1). Consequently, FUS-R521C mice exhibited evidence of DNA damage as well as profound dendritic and synaptic phenotypes in brain and spinal cord. To provide insights into these defects, we screened neural genes for nucleotide oxidation and identified brain-derived neurotrophic factor (Bdnf) as a target of FUS-R521C-associated DNA damage and RNA splicing defects in mice. Compared with WT FUS, mutant FUS-R521C proteins formed a more stable complex with Bdnf RNA in electrophoretic mobility shift assays. Stabilization of the FUS/Bdnf RNA complex contributed to Bdnf splicing defects and impaired BDNF signaling through receptor TrkB. Exogenous BDNF only partially restored dendrite phenotype in FUS-R521C neurons, suggesting that BDNF-independent mechanisms may contribute to the defects in these neurons. Indeed, RNA-seq analyses of FUS-R521C spinal cords revealed additional transcription and splicing defects in genes that regulate dendritic growth and synaptic functions. Together, our results provide insight into how gain-of-function FUS mutations affect critical neuronal functions.

  4. The oxidative damage and inflammation caused by pesticides are reverted by lipoic acid in rat brain.

    PubMed

    Astiz, Mariana; de Alaniz, María J T; Marra, Carlos Alberto

    2012-12-01

    We have previously demonstrated that the administration of low doses of dimethoate, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for 5weeks) provokes severe oxidative stress (OS) in specific brain regions: substantia nigra, cortex and hippocampus. These effects were also observed in plasma. Lipoic acid (LA) is considered an "ideal antioxidant" due to its ability to scavenge reactive species, reset antioxidant levels and cross the blood-brain barrier. To investigate its protective effect we administered LA (i.p. 25, 50 and 100mg/kg) simultaneously with the pesticide mixture (PM) for 5weeks. After suppression of PM administration, we evaluated the restorative effect of LA for a further 5weeks. LA prevented OS and the production of nitrites+nitrates [NOx] caused by PM in a dose-dependent manner. The PM-induced decrease in reduced glutathione and α-tocopherol levels in all brain regions was completely restored by LA at both high doses. PM administration also caused an increase in prostaglandins E(2) and F(2α) in brain that was reduced by LA in a dose-dependent fashion. Taking into account the relationship between OS, inflammation and apoptosis, we measured caspase and calpain activity. Only milli- and micro-calpain isoforms were increased in the PM-treated group and LA reduced the activities to basal levels. We also demonstrated that interrupting PM administration is not enough to restore the levels of all the parameters measured and that LA is necessary to achieve basal status. In our experimental model LA displayed a protective role against pesticide-induced damage, suggesting that LA administration is a promising therapeutic strategy to cope with disorders suspected to be caused by OS generators, especially in brain.

  5. DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells.

    PubMed

    Yedjou, Clement G; Tchounwou, Hervey M; Tchounwou, Paul B

    2015-12-22

    In recent years, the industrial use of lead has been significantly reduced from paints and ceramic products, caulking, and pipe solder. Despite this progress, lead exposure continues to be a significant public health concern. The main goal of this research was to determine the in vitro mechanisms of lead nitrate [Pb(NO₃)₂] to induce DNA damage, apoptosis, and cell cycle arrest in human leukemia (HL-60) cells. To reach our goal, HL-60 cells were treated with different concentrations of Pb(NO₃)₂ for 24 h. Live cells and necrotic death cells were measured by the propidium idiode (PI) assay using the cellometer vision. Cell apoptosis was measured by the flow cytometry and DNA laddering. Cell cycle analysis was evaluated by the flow cytometry. The result of the PI demonstrated a significant (p < 0.05) increase of necrotic cell death in Pb(NO₃)₂-treated cells, indicative of membrane rupture by Pb(NO₃)₂ compared to the control. Data generated from the comet assay indicated a concentration-dependent increase in DNA damage, showing a significant increase (p < 0.05) in comet tail-length and percentages of DNA cleavage. Data generated from the flow cytometry assessment indicated that Pb(NO₃)₂ exposure significantly (p < 0.05) increased the proportion of caspase-3 positive cells (apoptotic cells) compared to the control. The flow cytometry assessment also indicated Pb(NO₃)₂ exposure caused cell cycle arrest at the G₀/G₁ checkpoint. The result of DNA laddering assay showed presence of DNA smear in the agarose gel with little presence of DNA fragments in the treated cells compared to the control. In summary, Pb(NO₃)₂ inhibits HL-60 cells proliferation by not only inducing DNA damage and cell cycle arrest at the G₀/G₁ checkpoint but also triggering the apoptosis through caspase-3 activation and nucleosomal DNA fragmentation accompanied by secondary necrosis. We believe that our study provides a new insight into the mechanisms of Pb

  6. Topical application of ochratoxin A causes DNA damage and tumor initiation in mouse skin.

    PubMed

    Kumar, Rahul; Ansari, Kausar M; Chaudhari, Bhushan P; Dhawan, Alok; Dwivedi, Premendra D; Jain, Swatantra K; Das, Mukul

    2012-01-01

    Skin cancer is one of the most common forms of cancer and 2-3 million new cases are being diagnosed globally each year. Along with UV rays, environmental pollutants/chemicals including mycotoxins, contaminants of various foods and feed stuffs, could be one of the aetiological factors of skin cancer. In the present study, we evaluated the DNA damaging potential and dermal carcinogenicity of a mycotoxin, ochratoxin A (OTA), with the rationale that dermal exposure to OTA in workers may occur during their involvement in pre and post harvest stages of agriculture. A single topical application of OTA (20-80 µg/mouse) resulted in significant DNA damage along with elevated γ-H2AX level in skin. Alteration in oxidative stress markers such as lipid peroxidation, protein carbonyl, glutathione content and antioxidant enzymes was observed in a dose (20-80 µg/mouse) and time-dependent (12-72 h) manner. The oxidative stress was further emphasized by the suppression of Nrf2 translocation to nucleus following a single topical application of OTA (80 µg/mouse) after 24 h. OTA (80 µg/mouse) application for 12-72 h caused significant enhancement in- (a) reactive oxygen species generation, (b) activation of ERK1/2, p38 and JNK MAPKs, (c) cell cycle arrest at G0/G1 phase (37-67%), (d) induction of apoptosis (2.0-11.0 fold), (e) expression of p53, p21/waf1, (f) Bax/Bcl-2 ratio, (g) cytochrome c level, (h) activities of caspase 9 (1.2-1.8 fold) and 3 (1.7-2.2 fold) as well as poly ADP ribose polymerase cleavage. In a two-stage mouse skin tumorigenesis protocol, it was observed that a single topical application of OTA (80 µg/mouse) followed by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate for 24 week leads to tumor formation. These results suggest that OTA has skin tumor initiating property which may be related to oxidative stress, MAPKs signaling and DNA damage.

  7. DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells

    PubMed Central

    Yedjou, Clement G.; Tchounwou, Hervey M.; Tchounwou, Paul B.

    2015-01-01

    In recent years, the industrial use of lead has been significantly reduced from paints and ceramic products, caulking, and pipe solder. Despite this progress, lead exposure continues to be a significant public health concern. The main goal of this research was to determine the in vitro mechanisms of lead nitrate [Pb(NO3)2] to induce DNA damage, apoptosis, and cell cycle arrest in human leukemia (HL-60) cells. To reach our goal, HL-60 cells were treated with different concentrations of Pb(NO3)2 for 24 h. Live cells and necrotic death cells were measured by the propidium idiode (PI) assay using the cellometer vision. Cell apoptosis was measured by the flow cytometry and DNA laddering. Cell cycle analysis was evaluated by the flow cytometry. The result of the PI demonstrated a significant (p < 0.05) increase of necrotic cell death in Pb(NO3)2-treated cells, indicative of membrane rupture by Pb(NO3)2 compared to the control. Data generated from the comet assay indicated a concentration-dependent increase in DNA damage, showing a significant increase (p < 0.05) in comet tail-length and percentages of DNA cleavage. Data generated from the flow cytometry assessment indicated that Pb(NO3)2 exposure significantly (p < 0.05) increased the proportion of caspase-3 positive cells (apoptotic cells) compared to the control. The flow cytometry assessment also indicated Pb(NO3)2 exposure caused cell cycle arrest at the G0/G1 checkpoint. The result of DNA laddering assay showed presence of DNA smear in the agarose gel with little presence of DNA fragments in the treated cells compared to the control. In summary, Pb(NO3)2 inhibits HL-60 cells proliferation by not only inducing DNA damage and cell cycle arrest at the G0/G1 checkpoint but also triggering the apoptosis through caspase-3 activation and nucleosomal DNA fragmentation accompanied by secondary necrosis. We believe that our study provides a new insight into the mechanisms of Pb(NO3)2 exposure and its associated adverse health

  8. Scrum kidney: epidemic pyoderma caused by a nephritogenic Streptococcus pyogenes in a rugby team.

    PubMed

    Ludlam, H; Cookson, B

    1986-08-09

    In December, 1984, an outbreak of pyoderma affected five scrum players in the St Thomas' Hospital rugby team. The causative organism, Streptococcus pyogenes, was acquired during a match against a team experiencing an outbreak of impetigo, and was transmitted to two front row players of another team a week later, and to two girlfriends of affected St Thomas' players a month later. The strain was M-type 49, tetracycline-resistant, and virulent. It caused salpingitis in a girlfriend and acute glomerulonephritis in one rugby player. No case of subclinical glomerulonephritis was detected in eight patients with pyoderma. Screening of the St Thomas' Hospital team revealed four further cases of non-streptococcal skin infection, with evidence for contemporaneous spread of Staphylococcus aureus. Teams should not field players with sepsis, and it may be advisable to apply a skin antiseptic to traumatised skin after the match.

  9. Meta-Analysis of Attitudes toward Damage-Causing Mammalian Wildlife

    PubMed Central

    KANSKY, RUTH; KIDD, MARTIN; KNIGHT, ANDREW T

    2014-01-01

    Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments. Meta-Análisis de las Posturas hacia la Mam

  10. Polycystic Kidney Disease

    MedlinePlus

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  11. ACUTE KIDNEY INJURY CAUSED BY Crotalus AND Bothrops SNAKE VENOM: A REVIEW OF EPIDEMIOLOGY, CLINICAL MANIFESTATIONS AND TREATMENT

    PubMed Central

    Albuquerque, Polianna L.M.M.; Jacinto, Camilla N.; Silva, Geraldo B.; Lima, Juliana B.; Veras, Maria do Socorro B.; Daher, Elizabeth F.

    2013-01-01

    SUMMARY Ophidic accidents are an important public health problem due to their incidence, morbidity and mortality. An increasing number of cases have been registered in Brazil in the last few years. Several studies point to the importance of knowing the clinical complications and adequate approach in these accidents. However, knowledge about the risk factors is not enough and there are an increasing number of deaths due to these accidents in Brazil. In this context, acute kidney injury (AKI) appears as one of the main causes of death and consequences for these victims, which are mainly young males working in rural areas. Snakes of the Bothrops and Crotalus genera are the main responsible for renal involvement in ophidic accidents in South America. The present study is a literature review of AKI caused by Bothrops and Crotalus snake venom regarding diverse characteristics, emphasizing the most appropriate therapeutic approach for these cases. Recent studies have been carried out searching for complementary therapies for the treatment of ophidic accidents, including the use of lipoic acid, simvastatin and allopurinol. Some plants, such as Apocynaceae, Lamiaceae and Rubiaceae seem to have a beneficial role in the treatment of this type of envenomation. Future studies will certainly find new therapeutic measures for ophidic accidents. PMID:24037282

  12. Fulminant and fatal encephalitis caused by Acanthamoeba in a kidney transplant recipient: case report and literature review.

    PubMed

    Satlin, M J; Graham, J K; Visvesvara, G S; Mena, H; Marks, K M; Saal, S D; Soave, R

    2013-12-01

    Acanthamoeba is the most common cause of granulomatous amebic encephalitis, a typically fatal condition that is classically described as indolent and slowly progressive. We report a case of Acanthamoeba encephalitis in a kidney transplant recipient that progressed to death within 3 days of symptom onset and was diagnosed at autopsy. We also review clinical characteristics, treatments, and outcomes of all published cases of Acanthamoeba encephalitis in solid organ transplant (SOT) recipients. Ten cases were identified, and the infection was fatal in 9 of these cases. In 6 patients, Acanthamoeba presented in a fulminant manner and death occurred within 2 weeks after the onset of neurologic symptoms. These acute presentations are likely related to immunodeficiencies associated with solid organ transplantation that result in an inability to control Acanthamoeba proliferation. Skin lesions may predate neurologic involvement and provide an opportunity for early diagnosis and treatment. Acanthamoeba is an under-recognized cause of encephalitis in SOT recipients and often presents in a fulminant manner in this population. Increased awareness of this disease and its clinical manifestations is essential to attain an early diagnosis and provide the best chance of cure.

  13. Acute kidney injury caused by Crotalus and Bothrops snake venom: a review of epidemiology, clinical manifestations and treatment.

    PubMed

    Albuquerque, Polianna L M M; Jacinto, Camilla N; Silva Junior, Geraldo B; Lima, Juliana B; Veras, Maria do Socorro B; Daher, Elizabeth F

    2013-01-01

    Ophidic accidents are an important public health problem due to their incidence, morbidity and mortality. An increasing number of cases have been registered in Brazil in the last few years. Several studies point to the importance of knowing the clinical complications and adequate approach in these accidents. However, knowledge about the risk factors is not enough and there are an increasing number of deaths due to these accidents in Brazil. In this context, acute kidney injury (AKI) appears as one of the main causes of death and consequences for these victims, which are mainly young males working in rural areas. Snakes of the Bothrops and Crotalus genera are the main responsible for renal involvement in ophidic accidents in South America. The present study is a literature review of AKI caused by Bothrops and Crotalus snake venom regarding diverse characteristics, emphasizing the most appropriate therapeutic approach for these cases. Recent studies have been carried out searching for complementary therapies for the treatment of ophidic accidents, including the use of lipoic acid, simvastatin and allopurinol. Some plants, such as Apocynaceae, Lamiaceae and Rubiaceae seem to have a beneficial role in the treatment of this type of envenomation. Future studies will certainly find new therapeutic measures for ophidic accidents.

  14. Smoking increases the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease.

    PubMed

    Nakamura, Koshi; Nakagawa, Hideaki; Murakami, Yoshitaka; Kitamura, Akihiko; Kiyama, Masahiko; Sakata, Kiyomi; Tsuji, Ichiro; Miura, Katsuyuki; Ueshima, Hirotsugu; Okamura, Tomonori

    2015-11-01

    Little is known about the magnitude and nature of the combined effect of chronic kidney disease (CKD) and smoking on cardiovascular diseases. We studied this in a Japanese population using a pooled analysis of 15,468 men and 19,154 women aged 40-89 years enrolled in 8 cohort studies. The risk of mortality from all-causes and cardiovascular disease was compared in 6 gender-specific categories of baseline CKD status (non-CKD or CKD) and smoking habits (lifelong never smoked, former smokers, or currently smoking). CKD was defined as a decreased level of estimated glomerular filtration rate (under 60 ml/min per 1.73 m(2)) and/or dipstick proteinuria. Hazard ratios were estimated for each category, relative to never smokers without CKD. During the follow-up period (mean 14.8 years), there were 6771 deaths, 1975 of which were due to cardiovascular diseases. In both men and women, current or former smokers with CKD had the first or second highest crude mortality rates from all-cause and cardiovascular diseases among the 6 categories. After adjustment for age and other major cardiovascular risk factors, the hazard ratios in male and female current smokers with CKD were 2.26 (95% confidence interval, 1.95-2.63) and 1.78 (1.36-2.32) for all-causes, and 2.66 (2.04-3.47) and 1.71 (1.10-2.67) for cardiovascular diseases, respectively. Thus, coexistence of CKD and smoking may markedly increase the risk of all-cause and cardiovascular mortality.

  15. Mutations in GANAB, Encoding the Glucosidase IIα Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease.

    PubMed

    Porath, Binu; Gainullin, Vladimir G; Cornec-Le Gall, Emilie; Dillinger, Elizabeth K; Heyer, Christina M; Hopp, Katharina; Edwards, Marie E; Madsen, Charles D; Mauritz, Sarah R; Banks, Carly J; Baheti, Saurabh; Reddy, Bharathi; Herrero, José Ignacio; Bañales, Jesús M; Hogan, Marie C; Tasic, Velibor; Watnick, Terry J; Chapman, Arlene B; Vigneau, Cécile; Lavainne, Frédéric; Audrézet, Marie-Pierre; Ferec, Claude; Le Meur, Yannick; Torres, Vicente E; Harris, Peter C

    2016-06-02

    Autosomal-dominant polycystic kidney disease (ADPKD) is a common, progressive, adult-onset disease that is an important cause of end-stage renal disease (ESRD), which requires transplantation or dialysis. Mutations in PKD1 or PKD2 (∼85% and ∼15% of resolved cases, respectively) are the known causes of ADPKD. Extrarenal manifestations include an increased level of intracranial aneurysms and polycystic liver disease (PLD), which can be severe and associated with significant morbidity. Autosomal-dominant PLD (ADPLD) with no or very few renal cysts is a separate disorder caused by PRKCSH, SEC63, or LRP5 mutations. After screening, 7%-10% of ADPKD-affected and ∼50% of ADPLD-affected families were genetically unresolved (GUR), suggesting further genetic heterogeneity of both disorders. Whole-exome sequencing of six GUR ADPKD-affected families identified one with a missense mutation in GANAB, encoding glucosidase II subunit α (GIIα). Because PRKCSH encodes GIIβ, GANAB is a strong ADPKD and ADPLD candidate gene. Sanger screening of 321 additional GUR families identified eight further likely mutations (six truncating), and a total of 20 affected individuals were identified in seven ADPKD- and two ADPLD-affected families. The phenotype was mild PKD and variable, including severe, PLD. Analysis of GANAB-null cells showed an absolute requirement of GIIα for maturation and surface and ciliary localization of the ADPKD proteins (PC1 and PC2), and reduced mature PC1 was seen in GANAB(+/-) cells. PC1 surface localization in GANAB(-/-) cells was rescued by wild-type, but not mutant, GIIα. Overall, we show that GANAB mutations cause ADPKD and ADPLD and that the cystogenesis is most likely driven by defects in PC1 maturation.

  16. On the monitoring and implications of growing damages caused by manufacturing defects in composite structures

    NASA Astrophysics Data System (ADS)

    Schagerl, M.; Viechtbauer, C.; Hörrmann, S.

    2015-07-01

    Damage tolerance is a classical safety concept for the design of aircraft structures. Basically, this approach considers possible damages in the structure, predicts the damage growth under applied loading conditions and predicts the following decrease of the structural strength. As a fundamental result the damage tolerance approach yields the maximum inspection interval, which is the time a damage grows from a detectable to a critical level. The above formulation of the damage tolerance safety concept targets on metallic structures where the damage is typically a simple fatigue crack. Fiber-reinforced polymers show a much more complex damage behavior, such as delaminationsin laminated composites. Moreover, progressive damage in composites is often initiated by manufacturing defects. The complex manufacturing processes for composite structures almost certainly yield parts with defects, e.g. pores in the matrix or undulations of fibers. From such defects growing damages may start after a certain time of operation. The demand to simplify or even avoid the inspection of composite structures has therefore led to a comeback of the traditional safe-life safety concept. The aim of the so-called safe-life flaw tolerance concept is a structure that is capable of carrying the static loads during operation, despite significant damages and after a representative fatigue load spectrum. A structure with this property does not need to be inspected, respectively monitored at all during its service life. However, its load carrying capability is thereby not fully utilized. This article presents the possible refinement of the state-of-the-art safe-life flaw tolerance concept for composite structures towards a damage tolerance approach considering also the influence of manufacturing defects on damage initiation and growth. Based on fundamental physical relations and experimental observations the challenges when developing damage growth and residual strength curves are discussed.

  17. Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy.

    PubMed

    Scarfe, Lauren; Rak-Raszewska, Aleksandra; Geraci, Stefania; Darssan, Darsy; Sharkey, Jack; Huang, Jiaguo; Burton, Neal C; Mason, David; Ranjzad, Parisa; Kenny, Simon; Gretz, Norbert; Lévy, Raphaël; Kevin Park, B; García-Fiñana, Marta; Woolf, Adrian S; Murray, Patricia; Wilm, Bettina

    2015-09-02

    Maximising the use of preclinical murine models of progressive kidney disease as test beds for therapies ideally requires kidney function to be measured repeatedly in a safe, minimally invasive manner. To date, most studies of murine nephropathy depend on unreliable markers of renal physiological function, exemplified by measuring blood levels of creatinine and urea, and on various end points necessitating sacrifice of experimental animals to assess histological damage, thus counteracting the principles of Replacement, Refinement and Reduction. Here, we applied two novel minimally invasive techniques to measure kidney function in SCID mice with adriamycin-induced nephropathy. We employed i) a transcutaneous device that measures the half-life of intravenously administered FITC-sinistrin, a molecule cleared by glomerular filtration; and ii) multispectral optoacoustic tomography, a photoacoustic imaging device that directly visualises the clearance of the near infrared dye, IRDye 800CW carboxylate. Measurements with either technique showed a significant impairment of renal function in experimental animals versus controls, with significant correlations with the proportion of scarred glomeruli five weeks after induction of injury. These technologies provide clinically relevant functional data and should be widely adopted for testing the efficacies of novel therapies. Moreover, their use will also lead to a reduction in experimental animal numbers.

  18. 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

  19. Kidney: polycystic kidney disease.

    PubMed

    Paul, Binu M; Vanden Heuvel, Gregory B

    2014-01-01

    Polycystic kidney disease (PKD) is a life-threatening genetic disorder characterized by the presence of fluid-filled cysts primarily in the kidneys. PKD can be inherited as autosomal recessive (ARPKD) or autosomal dominant (ADPKD) traits. Mutations in either the PKD1 or PKD2 genes, which encode polycystin 1 and polycystin 2, are the underlying cause of ADPKD. Progressive cyst formation and renal enlargement lead to renal insufficiency in these patients, which need to be managed by lifelong dialysis or renal transplantation. While characteristic features of PKD are abnormalities in epithelial cell proliferation, fluid secretion, extracellular matrix and differentiation, the molecular mechanisms underlying these events are not understood. Here we review the progress that has been made in defining the function of the polycystins, and how disruption of these functions may be involved in cystogenesis.

  20. Pumping bottom water to prevent Korean red tide damage caused by Cochlodinium polykrikoides Margalef.

    PubMed

    Cho, Eun Seob; Moon, Seong Yong; Shu, Young Sang; Hwang, Jae Dong; Youn, Seok Hyun

    2015-09-01

    Cochlodinium polykrikoides Margalef produces annual massive blooms in Korean coastal waters which cause great damage to aquaculture and fisheries. Although various methods have been developed to remove the red tide of C. polykrikoides, release of yellow loess has been regarded as the most desirable technique for mitigation for over 10 years. Each August, strong irradiation generates water column stratification separating warm surface from colder bottom waters. Water from a distance of 0 (St. 1), 5 (St. 2), 10 (St. 3), and 15 m (St. 4) was pumped by running a pump for 0, 10, 30 and 90 min and characterized water temperature, salinity collected, suspended solids, Chl-a, and phytoplankton including C. polykrikoides. After running for 30 min, was temperature and salinity in surface water was similar to those of bottom water, and water column stratification completely reversed after 90 min. Likewise, suspended solids, Chl-a, and total phytoplankton cell density decreased after 30 min, but C. polykrikoides did not show strong removal because of low cell density during sampling. However, the number of C. polykrikoides was significantly diluted (80%) after 90 min. These results suggested that pumping device was as an environmentally-friendly method convenient to be install in fish cages and effective to remove C. polykrikoides stratified water column conditions.

  1. A fatal waterborne outbreak of pesticide poisoning caused by damaged pipelines, sindhikela, bolangir, orissa, India, 2008.

    PubMed

    Panda, Manjubala; Hutin, Yvan J; Ramachandran, Vidya; Murhekar, Manoj

    2009-01-01

    Introduction. We investigated a cluster of pesticide poisoning in Orissa. Methods. We searched the village for cases of vomiting and sweating on 2 February 2008. We described the outbreak by time, place, and person. We compared cases with controls. Results. We identified 65 cases (two deaths; attack rate: 12 per 1000; case fatality: 3%). The epidemic curve suggested a point source outbreak, and cases clustered close to a roadside eatery. Consumption of water from a specific source (odds ratio [OR]: 35, confidence interval [CI]: 13-93) and eating in the eatery (OR: 2.3, CI: 1.1-4.7) was associated with illness. On 31 January 2008, villagers had used pesticides to kill street dogs and had discarded leftovers in the drains. Damaged pipelines located beneath and supplying water may have aspirated the pesticide during the nocturnal negative pressure phase and rinsed it off the next morning in the water supply. Conclusions. Innapropriate use of pesticides contaminated the water supply and caused this outbreak. Education programs and regulations need to be combined to ensure a safer use of pesticides in India.

  2. Chronic Kidney Disease.

    PubMed

    Webster, Angela C; Nagler, Evi V; Morton, Rachael L; Masson, Philip

    2017-03-25

    The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m(2), or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR

  3. De Novo Kidney Regeneration with Stem Cells

    PubMed Central

    Yokote, Shinya; Yamanaka, Shuichiro; Yokoo, Takashi

    2012-01-01

    Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair and de novo whole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration. PMID:23251079

  4. Distinct illusory own-body perceptions caused by damage to posterior insula and extrastriate cortex.

    PubMed

    Heydrich, Lukas; Blanke, Olaf

    2013-03-01

    Recent research in cognitive neuroscience using virtual reality, robotic technology and brain imaging has linked self-consciousness to the processing and integration of multisensory bodily signals. This work on bodily self-consciousness has implicated the temporo-parietal, premotor and extrastriate cortex and partly originated in work on neurological patients with different disorders of bodily self-consciousness. One class of such disorders is autoscopic phenomena, which are defined as illusory own-body perceptions, during which patients experience the visual illusory reduplication of their own body in extrapersonal space. Three main forms of autoscopic phenomena have been defined. During autoscopic hallucinations, a second own body is seen without any changes in bodily self-consciousness. During out-of-body experiences, the second own body is seen from an elevated perspective and location associated with disembodiment. During heautoscopy, subjects report strong self-identification with the second own body, often associated with the experience of existing at and perceiving the world from two places at the same time. Although it has been proposed that each autoscopic phenomenon is associated with different impairments of bodily self-consciousness, past research on neurological patients and the development of experimental paradigms for the study of bodily self-consciousness has focused on out-of-body experiences and the association with temporo-parietal cortex. Here, we performed quantitative lesion analysis in the-to date-largest group of patients with autoscopic hallucination and heautoscopy and compared the location of brain damage with those of control patients suffering from complex visual hallucinations. We found that heautoscopy was associated with lesions to the left posterior insula, and that autoscopic hallucinations were associated with damage to the right occipital cortex. Autoscopic hallucination and heautoscopy were further associated with distinct

  5. Cardiac troponin and C-reactive protein for predicting all-cause and cardiovascular mortality in patients with chronic kidney disease: A meta-analysis

    PubMed Central

    Li, Wei-Jie; Chen, Xu-Miao; Nie, Xiao-Ying; Zhang, Jing; Cheng, Yun-Jiu; Lin, Xiao-Xiong; Wu, Su-Hua

    2015-01-01

    Elevated serum levels of cardiac troponin and C-reactive protein are associated with all-cause and cardiovascular mortality in patients with end-stage renal disease. However, the relationship between these two biomarker levels and mortality in patients with chronic kidney disease remains unclear. We conducted a meta-analysis to quantify the association of cardiac troponin and C-reactive protein levels with all-cause and cardiovascular mortality in patients with chronic kidney disease. Relevant studies were identified by searching the MEDLINE database through November 2013. Studies were included in the meta-analysis if they reported the long-term all-cause or cardiovascular mortality of chronic kidney disease patients with abnormally elevated serum levels of cardiac troponin or C-reactive protein. Summary estimates of association were obtained using a random-effects model. Thirty-two studies met our inclusion criteria. From the pooled analysis, cardiac troponin and C-reactive protein were significantly associated with all-cause (HR 2.93, 95% CI 1.97-4.33 and HR 1.21, 95% CI 1.14-1.29, respectively) and cardiovascular (HR 3.27, 95% CI 1.67-6.41 and HR 1.19, 95% CI 1.10-1.28, respectively) mortality. In the subgroup analysis of cardiac troponin and C-reactive protein, significant heterogeneities were found among the subgroups of population for renal replacement therapy and for the proportion of smokers and the C-reactive protein analysis method. Elevated serum levels of cardiac troponin and C-reactive protein are significant associated with higher risks of all-cause and cardiovascular mortality in patients with chronic kidney disease. Further studies are warranted to explore the risk stratification in chronic kidney disease patients. PMID:26017799

  6. Cardiac troponin and C-reactive protein for predicting all-cause and cardiovascular mortality in patients with chronic kidney disease: a meta-analysis.

    PubMed

    Li, Wei-Jie; Chen, Xu-Miao; Nie, Xiao-Ying; Zhang, Jing; Cheng, Yun-Jiu; Lin, Xiao-Xiong; Wu, Su-Hua

    2015-04-01

    Elevated serum levels of cardiac troponin and C-reactive protein are associated with all-cause and cardiovascular mortality in patients with end-stage renal disease. However, the relationship between these two biomarker levels and mortality in patients with chronic kidney disease remains unclear. We conducted a meta-analysis to quantify the association of cardiac troponin and C-reactive protein levels with all-cause and cardiovascular mortality in patients with chronic kidney disease. Relevant studies were identified by searching the MEDLINE database through November 2013. Studies were included in the meta-analysis if they reported the long-term all-cause or cardiovascular mortality of chronic kidney disease patients with abnormally elevated serum levels of cardiac troponin or C-reactive protein. Summary estimates of association were obtained using a random-effects model. Thirty-two studies met our inclusion criteria. From the pooled analysis, cardiac troponin and C-reactive protein were significantly associated with all-cause (HR 2.93, 95% CI 1.97-4.33 and HR 1.21, 95% CI 1.14-1.29, respectively) and cardiovascular (HR 3.27, 95% CI 1.67-6.41 and HR 1.19, 95% CI 1.10-1.28, respectively) mortality. In the subgroup analysis of cardiac troponin and C-reactive protein, significant heterogeneities were found among the subgroups of population for renal replacement therapy and for the proportion of smokers and the C-reactive protein analysis method. Elevated serum levels of cardiac troponin and C-reactive protein are significant associated with higher risks of all-cause and cardiovascular mortality in patients with chronic kidney disease. Further studies are warranted to explore the risk stratification in chronic kidney disease patients.

  7. Prevalence of chronic kidney disease of non-traditional causes in patients on hemodialysis in southwest Guatemala.

    PubMed

    Laux, Timothy S; Barnoya, Joaquin; Cipriano, Ever; Herrera, Erick; Lopez, Noemi; Polo, Vicente Sanchez; Rothstein, Marcos

    2016-04-01

    Objective To document the prevalence of patients on hemodialysis in southwestern Guatemala who have chronic kidney disease (CKD) of non-traditional causes (CKDnt). Methods This cross-sectional descriptive study interviewed patients on hemodialysis at the Instituto Guatemalteco de Seguridad Social on their health and occupational history. Laboratory serum, urine and vital sign data at the initiation of hemodialysis were obtained from chart reviews. Patients were classified according to whether they had hypertension or obesity or neither. The proportion of patients with and without these traditional CKD risk factors was recorded and the association between demographic and occupational factors and a lack of traditional CKD risk factors analyzed using multivariate logistic regression. Results Of 242 total patients (including 171 non-diabetics) enrolled in hemodialysis in southwestern Guatemala, 45 (18.6% of total patients and 26.3% of non-diabetics) lacked traditional CKD risk factors. While agricultural work history was common, only travel time greater than 30 minutes and age less than 50 years old were significantly associated with CKD in the absence of traditional risk factors. Individuals without such risk factors lived throughout southwestern Guatemala's five departments. Conclusions The prevalence of CKDnT appears to be much lower in this sample of patients receiving hemodialysis in Southwestern Guatemala than in hospitalized patients in El Salvador. It has yet to be determined whether the prevalence is higher in the general population and in patients on peritoneal dialysis.

  8. PRKX, TTBK2 and RSK4 expression causes Sunitinib resistance in kidney carcinoma- and melanoma-cell lines.

    PubMed

    Bender, Claus; Ullrich, Axel

    2012-07-15

    Resistance to chemotherapeutic agents constitutes a major problem in the treatment of cancer. Over the past years, multi-targeted protein kinase inhibitors such as Gleevec, Sunitinib and Sorafenib are gaining wider acceptance for cancer treatment. These drugs show anti-tumor activity in vitro and in patients. Extended usage of these drugs in therapy commonly results in disease progression due to formation of resistance caused by rearrangements and accumulation of mutations in the unstable cancer cell genome. However, the underlying drug-specific mechanisms for the development of resistance remain elusive. Hence, a detailed understanding of the molecular genetic events involved in this processes is pivotal to counteract are not directly targeted by Sunitinib (unpublished data). Therefore, development of specific or multi-targeted inhibitors for these kinases for combinatorial therapy with e.g., an IL-8 neutralizing antibody might circumvent or substantially delay Sunitinib resistance formation and enhance survival prognosis. PRKX, TTBK2 and RSK4 expression. The specific reduction of these genes employing siRNA was sufficient to sensitize the kidney- and melanoma-cell lines against Sunitinib. In line with the elevated expression of PRKX, TTBK2 or RSK4, this sensitization effect was strikingly higher in the Sunitinib resistant cell lines, suggesting an expression-based mechanism of these genes to trigger Sunitinib resistance. Hence, we propose that PRKX, TTBK2 and RSK4 are potential resistance markers in Sunitinib therapy and might therefore represent targets for the development of novel strategies to overcome resistance.

  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. Protective Effects of an Ancient Chinese Kidney-Tonifying Formula against H2O2-Induced Oxidative Damage to MES23.5 Cells

    PubMed Central

    Lin, Wei; Wang, Huajin; Wang, Tingting; Su, Youyan; Wu, Liangning; Wang, Yuanwang; Xu, Qian; Xu, Chuanshan

    2017-01-01

    Oxidative damage plays a critical role in the etiology of neurodegenerative disorders including Parkinson's disease (PD). In our study, an ancient Chinese kidney-tonifying formula, which consists of Cistanche, Epimedii, and Polygonatum cirrhifolium, was investigated to protect MES23.5 dopaminergic neurons against hydrogen peroxide- (H2O2-) induced oxidative damage. The damage effects of H2O2 on MES23.5 cells and the protective effects of KTF against oxidative stress were evaluated using MTT assay, transmission electron microscopy (TEM), immunocytochemistry (ICC), enzyme-linked immunosorbent assay (ELISA), and immunoblotting. The results showed that cell viability was dramatically decreased after a 12 h exposure to 150 μM H2O2. TEM observation found that the H2O2-treated MES23.5 cells presented cellular organelle damage. However, when cells were incubated with KTF (3.125, 6.25, and 12.5 μg/ml) for 24 h after H2O2 exposure, a significant protective effect against H2O2-induced damage was observed in MES23.5 cells. Using ICC, we found that KTF inhibited the reduction of the tyrosine hydroxylase (TH) induced by H2O2, upregulated the mRNA and protein expression of HO-1, CAT, and GPx-1, and downregulated the expression of caspase 3. These results indicated that KTF may provide neuron protection against H2O2-induced cell damage through ameliorating oxidative stress, and our findings provide a new potential strategy for the prevention and treatment of Parkinson's disease. PMID:28386511

  11. Optical Coherence Tomography in Kidney Transplantation

    NASA Astrophysics Data System (ADS)

    Andrews, Peter M.; Wierwille, Jeremiah; Chen, Yu

    End-stage renal disease (ESRD) is associated with both high mortality rates and an enormous economic burden [1]. The preferred treatment option for ESRD that can extend patients' lives and improve their quality of life is kidney transplantation. However, organ shortages continue to pose a major problem in kidney transplantation. Most kidneys for transplantation come from heart-beating cadavers. Although non-heart-beating cadavers represent a potentially large pool of donor kidneys, these kidneys are not often used due to the unknown extent of damage to the renal tubules (i.e., acute tubular necrosis or "ATN") induced by ischemia (i.e., lack of blood flow). Also, ischemic insult suffered by kidneys awaiting transplantation frequently causes ATN that leads to varying degrees of delayed graft function (DGF) after transplantation. Finally, ATN represents a significant risk for eventual graft and patient survival [2, 3] and can be difficult to discern from rejection. In present clinical practice, there is no reliable real-time test to determine the viability of donor kidneys and whether or not donor kidneys might exhibit ATN. Therefore, there is a critical need for an objective and reliable real-time test to predict ATN to use these organs safely and utilize the donor pool optimally. In this review, we provided preliminary data indicating that OCT can be used to predict the post-transplant function of kidneys used in transplantation.

  12. 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

  13. Hypercalcemia and acute kidney injury caused by abuse of a parenteral veterinary compound containing vitamins A, D, and E.

    PubMed

    Rocha, Paulo Novis; Santos, Caroline Sancho; Avila, Maria Olinda; Neves, Carolina Lara; Bahiense-Oliveira, Marilia

    2011-12-01

    A previously healthy 19 year-old male presented to the hospital with anorexia, nausea, and vomiting. Laboratory studies were significant for hypercalcemia (peak calcium value of 14.8 mg/dL) and acute kidney injury (peak serum creatinine of 2.88 mg/dL). He admitted to using a parenteral formulation of vitamins A, D and E restricted for veterinary use containing 20,000,000 IU of vitamin A; 5,000,000 IU of vitamin D3; and 6,800 IU of vitamin E per 100 mL vial. The patient stated to have used close to 300 mL of the product over the preceding year. Interestingly, the young man was not interested in the massive amounts of vitamins that the product contained; he was only after the local effects of the oily vehicle. The swelling produced by the injection resulted in a silicone-like effect, which gave the impression of bigger muscles. Nevertheless, the product was absorbed and caused hypervitaminosis. The serum level of 25(OH) vitamin D was clearly elevated at 150 ng/mL (reference range from 30 to 60 ng/mL), but in most published cases of vitamin D toxicity, serum levels have been well above 200 ng/mL. His PTH level was undetectable and other potential causes of hypercalcemia were excluded. Therefore, we posit that the severity of the hypercalcemia observed in this case was the result of a synergistic effect of vitamins A and D. The patient was treated with normal saline, furosemide and zolendronic acid, with rapid normalization of calcium levels and renal function.

  14. Solitary Kidney

    MedlinePlus

    ... How They Work Kidney Disease A-Z Solitary Kidney What is a solitary kidney? When a person has only one kidney or ... ureter are removed (bottom right). What are the kidneys and what do they do? The kidneys are ...

  15. Cafeteria diet-induced obesity causes oxidative damage in white adipose.

    PubMed

    Johnson, Amy R; Wilkerson, Matthew D; Sampey, Brante P; Troester, Melissa A; Hayes, D Neil; Makowski, Liza

    2016-04-29

    Obesity continues to be one of the most prominent public health dilemmas in the world. The complex interaction among the varied causes of obesity makes it a particularly challenging problem to address. While typical high-fat purified diets successfully induce weight gain in rodents, we have described a more robust model of diet-induced obesity based on feeding rats a diet consisting of highly palatable, energy-dense human junk foods - the "cafeteria" diet (CAF, 45-53% kcal from fat). We previously reported that CAF-fed rats became hyperphagic, gained more weight, and developed more severe hyperinsulinemia, hyperglycemia, and glucose intolerance compared to the lard-based 45% kcal from fat high fat diet-fed group. In addition, the CAF diet-fed group displayed a higher degree of inflammation in adipose and liver, mitochondrial dysfunction, and an increased concentration of lipid-derived, pro-inflammatory mediators. Building upon our previous findings, we aimed to determine mechanisms that underlie physiologic findings in the CAF diet. We investigated the effect of CAF diet-induced obesity on adipose tissue specifically using expression arrays and immunohistochemistry. Genomic evidence indicated the CAF diet induced alterations in the white adipose gene transcriptome, with notable suppression of glutathione-related genes and pathways involved in mitigating oxidative stress. Immunohistochemical analysis indicated a doubling in adipose lipid peroxidation marker 4-HNE levels compared to rats that remained lean on control standard chow diet. Our data indicates that the CAF diet drives an increase in oxidative damage in white adipose tissue that may affect tissue homeostasis. Oxidative stress drives activation of inflammatory kinases that can perturb insulin signaling leading to glucose intolerance and diabetes.

  16. Mechanism of Action of Lung Damage Caused by a Nanofilm Spray Product

    PubMed Central

    Larsen, Søren T.; Dallot, Constantin; Larsen, Susan W.; Rose, Fabrice; Poulsen, Steen S.; Nørgaard, Asger W.; Hansen, Jitka S.; Sørli, Jorid B.; Nielsen, Gunnar D.; Foged, Camilla

    2014-01-01

    Inhalation of waterproofing spray products has on several occasions caused lung damage, which in some cases was fatal. The present study aims to elucidate the mechanism of action of a nanofilm spray product, which has been shown to possess unusual toxic effects, including an extremely steep concentration-effect curve. The nanofilm product is intended for application on non-absorbing flooring materials and contains perfluorosiloxane as the active film-forming component. The toxicological effects and their underlying mechanisms of this product were studied using a mouse inhalation model, by in vitro techniques and by identification of the binding interaction. Inhalation of the aerosolized product gave rise to increased airway resistance in the mice, as evident from the decreased expiratory flow rate. The toxic effect of the waterproofing spray product included interaction with the pulmonary surfactants. More specifically, the active film-forming components in the spray product, perfluorinated siloxanes, inhibited the function of the lung surfactant due to non-covalent interaction with surfactant protein B, a component which is crucial for the stability and persistence of the lung surfactant film during respiration. The active film-forming component used in the present spray product is also found in several other products on the market. Hence, it may be expected that these products may have a toxicity similar to the waterproofing product studied here. Elucidation of the toxicological mechanism and identification of toxicological targets are important to perform rational and cost-effective toxicological studies. Thus, because the pulmonary surfactant system appears to be an important toxicological target for waterproofing spray products, study of surfactant inhibition could be included in toxicological assessment of this group of consumer products. PMID:24863969

  17. Schinus terebinthifolius Leaf Extract Causes Midgut Damage, Interfering with Survival and Development of Aedes aegypti Larvae

    PubMed Central

    Procópio, Thamara Figueiredo; Fernandes, Kenner Morais; Pontual, Emmanuel Viana; Ximenes, Rafael Matos; de Oliveira, Aline Rafaella Cardoso; Souza, Carolina de Santana; Melo, Ana Maria Mendonça de Albuquerque; Navarro, Daniela Maria do Amaral Ferraz; Paiva, Patrícia Maria Guedes; Martins, Gustavo Ferreira; Napoleão, Thiago Henrique

    2015-01-01

    In this study, a leaf extract from Schinus terebinthifolius was evaluated for effects on survival, development, and midgut of A. aegypti fourth instar larvae (L4), as well as for toxic effect on Artemia salina. Leaf extract was obtained using 0.15 M NaCl and evaluated for phytochemical composition and lectin activity. Early L4 larvae were incubated with the extract (0.3–1.35%, w/v) for 8 days, in presence or absence of food. Polymeric proanthocyanidins, hydrolysable tannins, heterosid and aglycone flavonoids, cinnamic acid derivatives, traces of steroids, and lectin activity were detected in the extract, which killed the larvae at an LC50 of 0.62% (unfed larvae) and 1.03% (fed larvae). Further, the larvae incubated with the extract reacted by eliminating the gut content. No larvae reached the pupal stage in treatments at concentrations between 0.5% and 1.35%, while in the control (fed larvae), 61.7% of individuals emerged as adults. The extract (1.0%) promoted intense disorganization of larval midgut epithelium, including deformation and hypertrophy of cells, disruption of microvilli, and vacuolization of cytoplasms, affecting digestive, enteroendocrine, regenerative, and proliferating cells. In addition, cells with fragmented DNA were observed. Separation of extract components by solid phase extraction revealed that cinnamic acid derivatives and flavonoids are involved in larvicidal effect of the extract, being the first most efficient in a short time after larvae treatment. The lectin present in the extract was isolated, but did not show deleterious effects on larvae. The extract and cinnamic acid derivatives were toxic to A. salina nauplii, while the flavonoids showed low toxicity. S. terebinthifolius leaf extract caused damage to the midgut of A. aegypti larvae, interfering with survival and development. The larvicidal effect of the extract can be attributed to cinnamic acid derivatives and flavonoids. The data obtained using A. salina indicates that caution

  18. Endotoxin-induced lung alveolar cell injury causes brain cell damage

    PubMed Central

    Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia RM; Pelosi, Paolo

    2015-01-01

    Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. PMID:25135986

  19. Heme-induced contractile dysfunction in human cardiomyocytes caused by oxidant damage to thick filament proteins.

    PubMed

    Alvarado, Gerardo; Jeney, Viktória; Tóth, Attila; Csősz, Éva; Kalló, Gergő; Huynh, An T; Hajnal, Csaba; Kalász, Judit; Pásztor, Enikő T; Édes, István; Gram, Magnus; Akerström, Bo; Smith, Ann; Eaton, John W; Balla, György; Papp, Zoltán; Balla, József

    2015-12-01

    Intracellular free heme predisposes to oxidant-mediated tissue damage. We hypothesized that free heme causes alterations in myocardial contractility via disturbed structure and/or regulation of the contractile proteins. Isometric force production and its Ca(2+)-sensitivity (pCa50) were monitored in permeabilized human ventricular cardiomyocytes. Heme exposure altered cardiomyocyte morphology and evoked robust decreases in Ca(2+)-activated maximal active force (Fo) while increasing Ca(2+)-independent passive force (F passive). Heme treatments, either alone or in combination with H2O2, did not affect pCa50. The increase in F passive started at 3 µM heme exposure and could be partially reversed by the antioxidant dithiothreitol. Protein sulfhydryl (SH) groups of thick myofilament content decreased and sulfenic acid formation increased after treatment with heme. Partial restoration in the SH group content was observed in a protein running at 140 kDa after treatment with dithiothreitol, but not in other proteins, such as filamin C, myosin heavy chain, cardiac myosin binding protein C, and α-actinin. Importantly, binding of heme to hemopexin or alpha-1-microglobulin prevented its effects on cardiomyocyte contractility, suggesting an allosteric effect. In line with this, free heme directly bound to myosin light chain 1 in human cardiomyocytes. Our observations suggest that free heme modifies cardiac contractile proteins via posttranslational protein modifications and via binding to myosin light chain 1, leading to severe contractile dysfunction. This may contribute to systolic and diastolic cardiac dysfunctions in hemolytic diseases, heart failure, and myocardial ischemia-reperfusion injury.

  20. Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease: a nested case–control study

    PubMed Central

    Ramesh, Ganesan; Jayakumar, Calpurnia; Leoncini, Giovanna; Garneri, Debora; Pontremoli, Roberto

    2014-01-01

    Background Semaphorins are guidance proteins implicated in several processes such as angiogenesis, organogenesis, cell migration, and cytokine release. Experimental studies showed that semaphorin-3a (SEMA3A) administration induces transient massive proteinuria, podocyte foot process effacement and endothelial cell damage in healthy animals. While SEMA3A signaling has been demonstrated to be mechanistically involved in experimental diabetic glomerulopathy and in acute kidney injury, to date its role in human chronic kidney disease (CKD) has not been investigated. Methods To test the hypothesis that SEMA3A may play a role in human CKD, we performed a cross-sectional, nested, case–control study on 151 matched hypertensive patients with and without CKD. SEMA3A was quantified in the urine (USEMA) by ELISA. Glomerular filtration rate was estimated (eGFR) by the CKD-EPI formula and albuminuria was measured as albumin-to-creatinine ratio (ACR). Results USEMA levels were positively correlated with urine ACR (p = 0.001) and serum creatinine (p < 0.001). USEMA was higher in patients with both components of renal damage as compared to those with only one and those with normal renal function (p < 0.007 and <0.001, respectively). The presence of increased USEMA levels (i.e. top quartile) entailed a fourfold higher risk of combined renal damage (p < 0.001) and an almost twofold higher risk of macroalbuminuria (p = 0.005) or of reduced eGFR, even adjusting for confounding factors (p = 0.002). Conclusions USEMA is independently associated with CKD in both diabetic and non diabetic hypertensive patients. Further studies may help clarify the mechanisms underlying this association and possibly the pathogenic changes leading to the development of CKD. PMID:24756974

  1. Semi-auto assessment system on building damage caused by landslide disaster with high-resolution satellite and aerial images

    NASA Astrophysics Data System (ADS)

    Sun, Bo; Xu, Qihua; He, Jun; Ge, Fengxiang; Wang, Ying

    2015-10-01

    In recent years, earthquake and heavy rain have triggered more and more landslides, which have caused serious economic losses. The timely detection of the disaster area and the assessment of the hazard are necessary and primary for disaster mitigation and relief. As high-resolution satellite and aerial images have been widely used in the field of environmental monitoring and disaster management, the damage assessment by processing satellite and aerial images has become a hot spot of research work. The rapid assessment of building damage caused by landslides with high-resolution satellite or aerial images is the focus of this article. In this paper, after analyzing the morphological characteristics of the landslide disaster, we proposed a set of criteria for rating building damage, and designed a semi-automatic evaluation system. The system is applied to the satellite and aerial images processing. The performance of the experiments demonstrated the effectiveness of our system.

  2. A combined deficiency of vitamins E and C causes severe central nervous system damage in guinea pigs.

    PubMed

    Burk, Raymond F; Christensen, Joani M; Maguire, Mark J; Austin, Lori M; Whetsell, William O; May, James M; Hill, Kristina E; Ebner, Ford F

    2006-06-01

    A short period of combined deficiency of vitamins E and C causes profound central nervous system (CNS) dysfunction in guinea pigs. For this report, CNS histopathology was studied to define the nature and extent of injury caused by this double deficiency. Weanling guinea pigs were fed a vitamin E-deficient or -replete diet for 14 d. Then vitamin C was withdrawn from the diet of some guinea pigs. Four diet groups were thus formed: replete, vitamin E deficient, vitamin C deficient, and both vitamin E and C deficient. From 5 to 11 d after institution of the doubly deficient diet, 9 of 12 guinea pigs developed paralysis, and 2 more were found dead. The remaining guinea pig in the doubly deficient group and all animals in the other 3 groups survived without clinical impairment until the experiment was terminated at 13-15 d. Brains and spinal cords were serially sectioned and stained for examination. Only the combined deficiency produced damage in the CNS. The damage consisted mainly of nerve cell death, axonal degeneration, vascular injury, and associated glial cell responses. The spinal cord and the ventral pons in the brainstem were most severely affected, often exhibiting asymmetric cystic lesions. Several features of the lesions suggest that the primary damage was to blood vessels. These results indicate that the paralysis and death caused by combined deficiency of vitamins E and C in guinea pigs is caused by severe damage in the brainstem and spinal cord.

  3. Overexpressed heat shock protein 70 protects cells against DNA damage caused by ultraviolet C in a dose-dependent manner

    PubMed Central

    Niu, Piye; Liu, Lin; Gong, Zhiyong; Tan, Hao; Wang, Feng; Yuan, Jing; Feng, Youmei; Wei, Qingyi; Tanguay, Robert M; Wu, Tangchun

    2006-01-01

    Heat shock protein 70 (Hsp70) comprises proteins that have been reported to protect cells, tissues, and organisms against damage from a wide variety of stressful stimuli; however, little is known about whether Hsp70 protects against DNA damage. In this study, we investigated the relationship between Hsp70 expression and the levels of ultraviolet C (UVC)–induced DNA damage in A549 cells with normal, inhibited, and overexpressed Hsp70 levels. Hsp70 expression was inhibited by treatment with quercetin or overexpressed by transfection of plasmids harboring the hsp70 gene. The level of DNA damage was assessed by the comet assay. The results showed that the levels of DNA damage (shown as the percentage of comet cells) in A549 cells increased in all cells after exposure to an incident dose of 0, 10, 20, 40, and 80 J/m2 whether Hsp70 was inhibited or overexpressed. This response was dose dependent: a protection against UVC-induced DNA damage in cells with overexpressed Hsp70 was observed at UVC dose 20 J/ m2 with a maximum at 40 J/m2 when compared with cells with normal Hsp70 levels and in quercetin-treated cells. This differential protection disappeared at 80 J/m2. These results suggest that overexpressed Hsp70 might play a role in protecting A549 cells from DNA damage caused by UVC irradiation, with a threshold of protection from at UVC irradiation-induced DNA damage by Hsp70. The detailed mechanism how Hsp70 is involved in DNA damage and possible DNA repair warrants further investigation. PMID:16817322

  4. Slit2-Robo signaling in inflammation and kidney injury.

    PubMed

    Chaturvedi, Swasti; Robinson, Lisa A

    2015-04-01

    Acute kidney injury is an increasingly common global health problem and is associated with severe morbidity and mortality. In addition to facing high mortality rates, the survivors of acute kidney injury are at increased risk of developing chronic kidney disease and end-stage renal disease. Renal ischemia-reperfusion injury (IRI) is the most common cause of acute kidney injury, and results from impaired delivery of oxygen and nutrients to the kidney. Massive leukocyte influx into the post-ischemic kidney is one of the hallmarks of IRI. The recruited leukocytes exacerbate tissue damage and, if uncontrolled, initiate the progressive changes that lead to renal fibrosis and chronic kidney disease. Early on, recruitment and activation of platelets promotes microthrombosis in the injured kidney, further exacerbating kidney damage. The diversity, complexity, and multiplicity of pathways involved in leukocyte recruitment and platelet activation make it extremely challenging to control these processes, and past efforts have met with limited success in human trials. A generalized strategy to inhibit infiltration of inflammatory leukocytes and platelets, thereby reducing inflammation and injury, may prove to be more beneficial. In this review, we summarize recent findings demonstrating that the neuronal guidance cues, Slit and Roundabout (Robo), prevent the migration of multiple leukocyte subsets towards diverse inflammatory chemoattractants, and have potent anti-platelet functions in vitro and in vivo. These properties uniquely position Slit2 as a novel therapeutic that could be used to prevent acute kidney injury associated with IRI.

  5. Topiramate as a rare cause of reversible Fanconi syndrome and acute kidney injury: a case report and literature review

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    Topiramate (TPM) is a sulfa-derivative monosaccharide that has been used for multiple indications in the last several years. We describe a 53-year-old woman with known chronic kidney disease stage 2 and baseline creatinine of 1 mg/dL who developed acute kidney injury and proximal renal tubular dysfunction while on TPM for depression. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between TPM and acute kidney injury as well as proximal tubular dysfunction; these renal conditions resolved on withdrawal of TPM. To our knowledge, this is the first report of such a scenario. Patients receiving TPM therapy should be closely monitored for evidence of kidney dysfunction and electrolyte abnormalities. PMID:26908388

  6. Acute kidney injury during pregnancy.

    PubMed

    Van Hook, James W

    2014-12-01

    Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.

  7. Diabetes and Kidney Disease

    MedlinePlus

    ... disease of diabetes, or diabetic nephropathy. How does diabetes cause kidney disease? High blood glucose , also called ... I keep my kidneys healthy if I have diabetes? The best way to slow or prevent diabetes- ...

  8. Initial Pulmonary Respiration Causes Massive Diaphragm Damage and Hyper-CKemia in Duchenne Muscular Dystrophy Dog

    PubMed Central

    Nakamura, Akinori; Kobayashi, Masanori; Kuraoka, Mutsuki; Yuasa, Katsutoshi; Yugeta, Naoko; Okada, Takashi; Takeda, Shin'ichi

    2013-01-01

    The molecular mechanism of muscle degeneration in a lethal muscle disorder Duchene muscular dystrophy (DMD) has not been fully elucidated. The dystrophic dog, a model of DMD, shows a high mortality rate with a marked increase in serum creatine kinase (CK) levels in the neonatal period. By measuring serum CK levels in cord and venous blood, we found initial pulmonary respiration resulted in massive diaphragm damage in the neonates and thereby lead to the high serum CK levels. Furthermore, molecular biological techniques revealed that osteopontin was prominently upregulated in the dystrophic diaphragm prior to the respiration, and that immediate-early genes (c-fos and egr-1) and inflammation/immune response genes (IL-6, IL-8, COX-2, and selectin E) were distinctly overexpressed after the damage by the respiration. Hence, we segregated dystrophic phases at the molecular level before and after mechanical damage. These molecules could be biomarkers of muscle damage and potential targets in pharmaceutical therapies. PMID:23851606

  9. RLIP76 Targeted Therapy for Kidney Cancer.

    PubMed

    Singhal, Sharad S; Singhal, Jyotsana; Figarola, James; Horne, David; Awasthi, Sanjay

    2015-10-01

    Despite recent improvements in chemotherapeutic approaches to treating kidney cancer, this malignancy remains deadly if not found and removed at an early stage of the disease. Kidney cancer is highly drug-resistant, which may at least partially result from high expression of transporter proteins in the cell membranes of kidney cells. Although these transporter proteins can contribute to drug-resistance, targeting proteins from the ATP-binding cassette transporter family has not been effective in reversing drug-resistance in kidney cancer. Recent studies have identified RLIP76 as a key stress-defense protein that protects normal cells from damage caused by stress conditions, including heat, ultra-violet light, X-irradiation, and oxidant/electrophilic toxic chemicals, and is crucial for protecting cancer cells from apoptosis. RLIP76 is the predominant glutathione-electrophile-conjugate (GS-E) transporter in cells, and inhibiting it with antibodies or through siRNA or antisense causes apoptosis in many cancer cell types. To date, blocking of RLIP76, either alone or in combination with chemotherapeutic drugs, as a therapeutic strategy for kidney cancer has not yet been evaluated in human clinical trials, although there is considerable potential for RLIP76 to be developed as a therapeutic agent for kidney cancer. In the present review, we discuss the mechanisms underlying apoptosis caused by RLIP76 depletion, the role of RLIP76 in clathrin-dependent endocytosis deficiency, and the feasibility of RLIP76-targeted therapy for kidney cancer.

  10. Could humic acid relieve the biochemical toxicities and DNA damage caused by nickel and deltamethrin in earthworms (Eisenia foetida)?

    PubMed

    Shen, Chen-Chao; Shen, Dong-Sheng; Shentu, Jia-Li; Wang, Mei-Zhen; Wan, Ming-Yang

    2015-12-01

    The aim of the study was to determine whether humic acid (HA) prevented gene and biochemical toxic effects in earthworms (Eisenia foetida) exposed to nickel and deltamethrin (at 100 and 1 mg kg(-1), respectively) in soil. Cellular- and molecular-level toxic effects of nickel and deltamethrin in earthworms were evaluated by measuring damage to lipid membranes and DNA and the production of protein carbonyls over 42 days of exposure. Nickel and deltamethrin induced significant levels of oxidative stress in earthworms, increasing the production of peroxidation products (malondialdehyde and protein carbonyls) and increasing the comet assay tail DNA% (determined by single-cell gel electrophoresis). DNA damage was the most sensitive of the three indices because it gave a higher sample/control ratio than did the other indices. The presence of HA alleviated (in decreasing order of effectiveness) damage to DNA, proteins, and lipid membranes caused by nickel and deltamethrin. A low HA dose (0.5-1% HA in soil) prevented a great deal of lipid membrane damage, but the highest HA dose (3% HA in soil) prevented still more DNA damage. However, the malondialdehyde concentrations in earthworms were higher at the highest HA dose than at the lower HA doses. The amounts of protein carbonyls produced at different HA doses were not significantly different. The toxic effects to earthworms caused by increased oxidizable nickel concentrations could be relieved by adding HA.

  11. Natural sea salt consumption confers protection against hypertension and kidney damage in Dahl salt-sensitive rats

    PubMed Central

    Lee, Bog-Hieu; Yang, Ae-Ri; Kim, Mi Young; McCurdy, Sara; Boisvert, William A.

    2017-01-01

    ABSTRACT Although sea salts are widely available to consumers nowadays, whether its consumption over refined salt has any real health benefits is largely unknown. This study was conducted to compare hypertension-inducing propensity of natural sea salt (SS) to refined salt (RS) in a well-established animal model of hypertension. Five groups of male Dahl salt-sensitive rats were fed rat chow diet supplemented with various amounts of salt for 15 weeks. The groups were: control (CON, n = 10), 4% RS (RS4), 4% SS (SS4), 8% RS (RS8), 8% SS (SS8) (n = 12 for each group). After 15 weeks, both SS4 and SS8 groups had significantly lower systolic (SBP) and diastolic blood pressure (DBP) compared to RS4 and RS8 rats, respectively. RS8 rats had markedly higher SBP and DBP compared to all other groups. Echocardiography just prior to sacrifice showed abnormalities in RS4, SS8 and RS8 hearts, while CON and SS4 hearts displayed normal measurements. Plasma renin and aldosterone levels of high salt groups were lower than those of CON, and serum electrolytes were similar amongst all groups. Abnormal kidney pathology and high glomerulosclerosis index scores were seen in RS4 and RS8 rats, but SS4 and SS8 kidneys showed relatively normal morphology similar to CON kidneys. Our findings show that consumption of natural sea salt induces less hypertension compared to refined salt in the Dahl salt-sensitive rat. PMID:28325999

  12. DNA damage in the kidney tissue cells of the fish Rhamdia quelen after trophic contamination with aluminum sulfate

    PubMed Central

    Klingelfus, Tatiane; da Costa, Paula Moiana; Scherer, Marcos; Cestari, Marta Margarete

    2015-01-01

    Abstract Even though aluminum is the third most common element present in the earth's crust, information regarding its toxicity remains scarce. It is known that in certain cases, aluminum is neurotoxic, but its effect in other tissues is unknown. The aim of this work was to analyze the genotoxic potential of aluminum sulfate in kidney tissue of the fish Rhamdia quelen after trophic contamination for 60 days. Sixty four fish were subdivided into the following groups: negative control, 5 mg, 50 mg and 500 mg of aluminum sulfate per kg of fish. Samples of the posterior kidney were taken and prepared to obtain mitotic metaphase, as well as the comet assay. The three types of chromosomal abnormalities (CA) found were categorized as chromatid breaks, decondensation of telomeric region, and early separation of sister chromatids. The tests for CA showed that the 5 mg/kg and 50 mg/kg doses of aluminum sulfate had genotoxic potential. Under these treatments, early separation of the sister chromatids was observed more frequently and decondensation of the telomeric region tended to increase in frequency. We suggest that structural changes in the proteins involved in DNA compaction may have led to the decondensation of the telomeric region, making the DNA susceptible to breaks. Moreover, early separation of the sister chromatids may have occurred due to changes in the mobility of chromosomes or proteins that keep the sister chromatids together. The comet assay confirmed the genotoxicity of aluminum sulfate in the kidney tissue of Rhamdia quelen at the three doses of exposure. PMID:26692157

  13. The Role of Topography in the Distribution and Intensity of Damage Caused by Deer in Polish Mountain Forests

    PubMed Central

    Ciesielski, Mariusz; Stereńczak, Krzysztof; Borowski, Zbigniew

    2016-01-01

    The increase in the deer population observed in recent decades has strongly impacted forest regeneration and the forest itself. The reduction in the quality of raw wood material, as a consequence of deer-mediated damage, constitutes a significant burden on forest owners. The basis for the commencement of preventive actions in this setting is the understanding of the populations and behaviors of deer in their natural environment. Although multiple studies have been carried out regarding this subject, only a few suggested topography as an important factor that may influence the distribution and intensity of deer-mediated damage. The detailed terrain models based on LiDAR data as well as the data on damage caused by deer from the State Forests database enabled thorough analyses of the distribution and intensity of damage in relation to land form in this study. These analyses were performed on three mountain regions in Poland: the Western Sudety Mountains, the Eastern Sudety Mountains, and the Beskidy Mountains. Even though these three regions are located several dozen to several hundred kilometers apart from each other, not all evaluated factors appeared common among them, and therefore, these regions have been analyzed separately. The obtained results indicated that the forest damage caused by deer increased with increasing altitude above 1000 m ASL. However, much larger areas of damage by deer were observed at elevations ranging from 401 to 1000 m ASL than at elevations below 400 m ASL. Moreover, the locations of damage (forest thickets and old stands) indicated that red deer is the species that exerts the strongest pressure on forest ecosystems. Our results show the importance of deer foraging behavior to the structure of the environment. PMID:27851776

  14. The Role of Topography in the Distribution and Intensity of Damage Caused by Deer in Polish Mountain Forests.

    PubMed

    Bałazy, Radomir; Ciesielski, Mariusz; Stereńczak, Krzysztof; Borowski, Zbigniew

    2016-01-01

    The increase in the deer population observed in recent decades has strongly impacted forest regeneration and the forest itself. The reduction in the quality of raw wood material, as a consequence of deer-mediated damage, constitutes a significant burden on forest owners. The basis for the commencement of preventive actions in this setting is the understanding of the populations and behaviors of deer in their natural environment. Although multiple studies have been carried out regarding this subject, only a few suggested topography as an important factor that may influence the distribution and intensity of deer-mediated damage. The detailed terrain models based on LiDAR data as well as the data on damage caused by deer from the State Forests database enabled thorough analyses of the distribution and intensity of damage in relation to land form in this study. These analyses were performed on three mountain regions in Poland: the Western Sudety Mountains, the Eastern Sudety Mountains, and the Beskidy Mountains. Even though these three regions are located several dozen to several hundred kilometers apart from each other, not all evaluated factors appeared common among them, and therefore, these regions have been analyzed separately. The obtained results indicated that the forest damage caused by deer increased with increasing altitude above 1000 m ASL. However, much larger areas of damage by deer were observed at elevations ranging from 401 to 1000 m ASL than at elevations below 400 m ASL. Moreover, the locations of damage (forest thickets and old stands) indicated that red deer is the species that exerts the strongest pressure on forest ecosystems. Our results show the importance of deer foraging behavior to the structure of the environment.

  15. Alcohol metabolism in human cells causes DNA damage and activates the Fanconi anemia – breast cancer susceptibility (FA-BRCA) DNA damage response network

    PubMed Central

    Abraham, Jessy; Balbo, Silvia; Crabb, David; Brooks, P.J.

    2011-01-01

    Background We recently reported that exposure of human cells in vitro to acetaldehyde resulted in activation of the Fanconi anemia-breast cancer associated (FA-BRCA) DNA damage response network. Methods To determine whether intracellular generation of acetaldehyde from ethanol metabolism can cause DNA damage and activate the FA-BRCA network, we engineered HeLa cells to metabolize alcohol by expression of human alcohol dehydrogenase 1B. Results Incubation of HeLa-ADH1B cells with ethanol (20 mM) resulted in acetaldehyde accumulation in the media which was prevented by co-incubation with 4-methyl pyrazole (4-MP), a specific inhibitor of ADH. Ethanol treatment of HeLa-ADH1B cells produced a 4-fold increase in the acetaldehyde-DNA adduct, N2-ethylidene-dGuo, and also resulted in activation of the Fanconi anemia -breast cancer susceptibility (FA-BRCA) DNA damage response network, as indicated by a monoubiquitination of FANCD2, and phosphorylation of BRCA1. Ser 1524 was identified as one site of BRCA1 phosphorylation. The increased levels of DNA adducts, FANCD2 monoubiquitination, and BRCA1 phosphorylation were all blocked by 4-MP, indicating that acetaldehyde, rather than ethanol itself, was responsible for all three responses. Importantly, the ethanol concentration we used is within the range that can be attained in the human body during social drinking. Conclusions Our results indicate that intracellular metabolism of ethanol to acetaldehyde results in DNA damage which activates the FA-BRCA DNA damage response network. PMID:21919919

  16. Toward resolving an earthquake ground motion mystery in west Seattle, Washington State: Shallow seismic focusing may cause anomalous chimney damage

    USGS Publications Warehouse

    Stephenson, W.J.; Frankel, A.D.; Odum, J.K.; Williams, R.A.; Pratt, T.L.

    2006-01-01

    A shallow bedrock fold imaged by a 1.3-km long high-resolution shear-wave seismic reflection profile in west Seattle focuses seismic waves arriving from the south. This focusing may cause a pocket of amplified ground shaking and the anomalous chimney damage observed in earthquakes of 1949, 1965 and 2001. The 200-m bedrock fold at ???300-m depth is caused by deformation across an inferred fault within the Seattle fault zone. Ground motion simulations, using the imaged geologic structure and northward-propagating north-dipping plane wave sources, predict a peak horizontal acceleration pattern that matches that observed in strong motion records of the 2001 Nisqually event. Additionally, a pocket of chimney damage reported for both the 1965 and the 2001 earthquakes generally coincides with a zone of simulated amplification caused by focusing. This study further demonstrates the significant impact shallow (<1km) crustal structures can have on earthquake ground-motion variability.

  17. Smoking during pregnancy causes double-strand DNA break damage to the placenta.

    PubMed

    Slatter, Tania L; Park, Lydia; Anderson, Karyn; Lailai-Tasmania, Viwa; Herbison, Peter; Clow, William; Royds, Janice A; Devenish, Celia; Hung, Noelyn A

    2014-01-01

    Despite the adverse effects of smoking, many pregnancies are exposed to tobacco smoke. Recent studies have investigated whether smoking damages placental DNA by measuring DNA adducts. This study investigated whether a more severe lesion, double-strand DNA breaks, was also present in the tobacco smoking-exposed placenta. Term placentae from women who smoked during their entire pregnancies (n = 52), from those who had ceased smoking for at least 4 weeks before delivery (previous smokers, n = 34), and from nonsmoking women (n = 150) were examined using the DNA double-strand break marker phosphorylated γ H2AX. The extent of DNA damage was assessed according to cell type and additional markers were applied for cell fate (apoptosis and DNA repair), and function (human chorionic gonadotropin, human placental lactogen, and glucose transporter 1), to characterize the effect of the DNA damage on placental integrity. Marked phosphorylated γ H2AX-positive cells occurred in the villous syncytiotrophoblast and syncytial knot nuclei in placentae from smokers (P < .001). Phosphorylated γ H2AX foci did not colocalize with the DNA repair protein 53BP1, and damaged nuclei had a marked reduction in expression of human chorionic gonadotropin, human placental lactogen, and glucose transporter 1. Minimal DNA damage, similar to nonsmokers, was present in previous smokers including those that had ceased smoking for just over 4 weeks before delivery. In summary, smoking during pregnancy was associated with marked double-strand DNA break damage to the syncytiotrophoblast. We suggest that smoking cessation is important to prevent additional DNA damage and to facilitate DNA repair.

  18. Successful treatment of renal failure caused by multiple myeloma with HLA-identical living kidney and bone marrow transplantation: a case report.

    PubMed

    Wagner, L; Lengyel, L; Mikala, G; Reményi, P; Piros, L; Csomor, J; Fábry, L; Tordai, A; Langer, R M; Masszi, T

    2013-01-01

    Here we have described a successful HLA-identical living allogeneic kidney transplantation after bone marrow transplantation in a patient with end-stag liver disease caused by multiple myeloma (MM). Our case is unique, because this combined transplantation is rarely possible and because of our unique immunosuppressive and management strategies. A 45-year-old man with ESRD MM and κ light-chain nephropathy was diagnosed. Cytostatic treatment resulted in partial remission, so autologous peripheral stem cell transplantation (SCT) was performed leading to a complete remission; however the patient remained anuric. The patient's HLA-identical brother offered to be a donor of peripheral stem cells for collection and cryopreservation. Kidney transplantation was performed with a combination of tacrolimus sirolimuns, and methylprednisolone. With a well-functioning kidney graft, allogeneic SCT was performed in the incipient relapse phase of MM, after total body irradiation. Severe oropharyngeal infections, diarrhea, sepsis, and renal failure. Fearing acute renal rejection, we administered steroid bolus. He experienced therapy with gradual restoration of kidney function. Then, steroid-responsive acute graft-versus-host disease (grade II, predominantly bowel) was diagnosed on the background of diarrhea, which returned once. Later he experienced a left subclavian vein thrombosis at the site of a central venous catheter and sepsis. Having recovered from these events, the patient enjoys good health, with stable kidney function and normal protein excretion. After the steroid was stopped, a bone marrow biopsy revealed full-donor type normocellular hemopoiesis. Because of the chimerism, we gradually discontinued the immunosuppression including, sirolimus and finally tacrolimus, since with minimal trough levels there were no complications. Bone marrow biopsy showed a complete remission. In MM with ESRD HLA-identical combined kidney and bone marrow transplantation from a living donor

  19. Human kidney damage in fatal dengue hemorrhagic fever results of glomeruli injury mainly induced by IL17.

    PubMed

    Pagliari, Carla; Simões Quaresma, Juarez Antônio; Kanashiro-Galo, Luciane; de Carvalho, Leda Viegas; Vitoria, Webster Oliveira; da Silva, Wellington Luiz Ferreira; Penny, Ricardo; Vasconcelos, Barbara Cristina Baldez; da Costa Vasconcelos, Pedro Fernando; Duarte, Maria Irma Seixas

    2016-02-01

    Acute kidney injury is an unusual complication during dengue infection. The objective of this study was to better identify the characteristics of glomerular changes focusing on in situ immune cells and cytokines. An immunohistochemical assay was performed on 20 kidney specimens from fatal human cases of dengue hemorrhagic fever (DHF). It was observed a lymphomononuclear infiltrate, neutrophils and nuclear fragmentation in the glomeruli, hydropic degeneration, nuclear retraction, eosinophilic tubules and intense acute congestion. Sickle erythrocytes were frequent in glomeruli and inflammatory infiltrate. The glomeruli presented endothelial swelling and mesangial proliferation. Lymphocytes CD4+ predominated over CD8+ T cells, B cells and natural killer cells. There were also an expressive number of macrophagic CD68+ cells. S100, Foxp3 and CD123 cells were not identified. Cells expressing IL17 and IL18+ cytokines predominated in the renal tissues, while IL4, IL6, IL10, IL13, TNF-alpha and IFN-gamma were rarely visualized. The high number of cells expressing IL17 and IL18+ could reflect the acute inflammatory response and possibly contribute to the local lesion. CD8+ T cells could play a role in the cytotoxic response. DHF is a multifactorial disease of capillary leakage associated with a "Tsunami of cytokines expression". The large numbers of cells expressing IL17 seems to play a role favoring the increased permeability.

  20. De Novo Donor-Specific HLA Antibodies Developing Early or Late after Transplant Are Associated with the Same Risk of Graft Damage and Loss in Nonsensitized Kidney Recipients

    PubMed Central

    Cioni, Michela; Nocera, Arcangelo; Innocente, Annalisa; Tagliamacco, Augusto; Trivelli, Antonella; Basso, Sabrina; Quartuccio, Giuseppe; Fontana, Iris; Magnasco, Alberto; Drago, Francesca; Gurrado, Antonella; Guido, Ilaria; Compagno, Francesca; Garibotto, Giacomo; Klersy, Catherine; Verrina, Enrico; Ghiggeri, Gian Marco; Cardillo, Massimo

    2017-01-01

    De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24.6 months. In 15 patients, dnDSAs developed within 1 year (early-onset group), while the other 24 seroconverted after the first posttransplant year (late-onset group). The two groups were comparable when considering patient- and transplant-related factors, as well as DSA biological properties, including C1q and C3d complement-binding ability. Only recipient age at transplant significantly differed in the two cohorts, with younger patients showing earlier dnDSA development. Late AMR was diagnosed in 47% of the early group and in 58% of the late group. Graft loss occurred in 3/15 (20%) and 4/24 (17%) patients in early- and late-onset groups, respectively (p = ns). In our pediatric kidney recipients, dnDSAs predict AMR and graft loss irrespective of the time elapsed between transplantation and antibody occurrence. PMID:28367453

  1. Carotid Catheterization and Automated Blood Sampling Induce Systemic IL-6 Secretion and Local Tissue Damage and Inflammation in the Heart, Kidneys, Liver and Salivary Glands in NMRI Mice

    PubMed Central

    Teilmann, Anne Charlotte; Rozell, Björn; Kalliokoski, Otto; Hau, Jann; Abelson, Klas S. P.

    2016-01-01

    Automated blood sampling through a vascular catheter is a frequently utilized technique in laboratory mice. The potential immunological and physiological implications associated with this technique have, however, not been investigated in detail. The present study compared plasma levels of the cytokines IL-1β, IL-2, IL-6, IL-10, IL-17A, GM-CSF, IFN-γ and TNF-α in male NMRI mice that had been subjected to carotid artery catheterization and subsequent automated blood sampling with age-matched control mice. Body weight and histopathological changes in the surgical area, including the salivary glands, the heart, brain, spleen, liver, kidneys and lungs were compared. Catheterized mice had higher levels of IL-6 than did control mice, but other cytokine levels did not differ between the groups. No significant difference in body weight was found. The histology revealed inflammatory and regenerative (healing) changes at surgical sites of all catheterized mice, with mild inflammatory changes extending into the salivary glands. Several catheterized mice had multifocal degenerative to necrotic changes with inflammation in the heart, kidneys and livers, suggesting that thrombi had detached from the catheter tip and embolized to distant sites. Thus, catheterization and subsequent automated blood sampling may have physiological impact. Possible confounding effects of visceral damage should be assessed and considered, when using catheterized mouse models. PMID:27832170

  2. Dose-response relationship for rat liver DNA damage caused by 1,2-dimethylhydrazine.

    PubMed

    Kitchin, K T; Brown, J L

    1996-12-02

    An experimental approach was taken to the question of dose-response curves for chemical carcinogenesis, using DNA damage as a biomarker. Female rats were give 13 different doses of 1,2-dimethylhydrazine (from 1.4 to 135,000 micrograms/kg) and the subsequent hepatic DNA damage was determined by the alkaline elution technique. DMH doses below 450 micrograms/kg did not significantly damage DNA; all DMH doses of 1000 micrograms/kg or higher damaged rat hepatic DNA (P < 0.05). In this study the x values (dose) ranged over five orders of magnitude and the y values (DNA damage) ranged 30-fold. Ten different regression models (linear, quadratic, cubic, power, and six nonlinear transition models) were compared in their ability to fit the experimental data. With respect to log transformed dose, the six nonlinear transition equations fit the data considerably better than the four power type of equations. A sigmoid model fit to the log transformed dose of 1,2-dimethylhydrazine had an r2 of 0.9979, a degree of freedom adjusted r2 of 0.9969, a F-statistic of 1,457, and a fit standard error of 0.50. With respect to untransformed dose, only three equations (sigmoid, cascade and gaussian cumulative) could creditably fit the DMH data. The experimental results are interpreted with respect to hormesis, use of log transformed dose, sigmoid dose-response models, thresholds of biological response and cancer risk assessment.

  3. Two damaging hydrogeological events in Calabria, September 2000 and November 2015. Comparative analysis of causes and effects

    NASA Astrophysics Data System (ADS)

    Petrucci, Olga; Caloiero, Tommaso; Aurora Pasqua, Angela

    2016-04-01

    Each year, especially during winter season, some episode of intense rain affects Calabria, the southernmost Italian peninsular region, triggering flash floods and mass movements that cause damage and fatalities. This work presents a comparative analysis between two events that affected the southeast sector of the region, in 2000 and 2014, respectively. The event occurred between 9th and 10th of September 2000 is known in Italy as Soverato event, after the name of the municipality where it reached the highest damage severity. In the Soverato area, more than 200 mm of rain that fell in 24 hours caused a disastrous flood that swept away a campsite at about 4 a.m., killing 13 people and hurting 45. Besides, the rain affected a larger area, causing damage in 89 (out of 409) municipalities of the region. Flooding was the most common process, which damaged housing and trading. Landslide mostly affected the road network, housing and cultivations. The most recent event affected the same regional sector between 30th October and 2nd November 2015. The daily rain recorded at some of the rain gauges of the area almost reached 400 mm. Out of the 409 municipalities of Calabria, 109 suffered damage. The most frequent types of processes were both flash floods and landslides. The most heavily damaged element was the road network: the representative picture of the event is a railway bridge destroyed by the river flow. Housing was damaged too, and 486 people were temporarily evacuated from home. The event also caused a victim killed by a flood. The event-centred study approach aims to highlight differences and similarities in both the causes and the effects of the two events that occurred at a temporal distance of 14 years. The comparative analysis focus on three main aspects: the intensity of triggering rain, the modifications of urbanised areas, and the evolution of emergency management. The comparative analysis of rain is made by comparing the return period of both daily and

  4. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    SciTech Connect

    Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.; Altman, K.I.

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  5. Intragastric inulin as a measure of mucosal damage caused by aspirin

    SciTech Connect

    Wittmers, L.E. Jr.; Anderson, L.A.; Fall, M.M.; Alich, A.A. )

    1990-11-01

    In an attempt to find a method of gastric mucosal damage assessment that yields consistent results, the experiments presented here employed the measurement of the movement of inulin out of the gastric contents into the stomach wall and vascular compartment as an estimate of mucosal damage. Anesthetized male Sprague-Dawley rats were functionally nephrectomized and were administered a control or test solution containing 3H-inulin. The test solutions contained one of three doses of aspirin. Blood samples were taken at 15-min intervals over a 90-min exposure period. The stomach was removed from the animal and full-thickness tissue samples taken for measurement of 3H-inulin content. When the gastric mucosa was exposed to the test agents, there was a significantly greater accumulation of inulin in the body and antrum as well as in the plasma when compared to controls. We conclude that intragastric inulin can be employed to estimate gastric mucosal damage.

  6. Method for assessing damage to mitochondrial DNA caused by radiation and epichlorohydrin

    SciTech Connect

    Singh, G.; Hauswirth, W.W.; Ross, W.E.; Neims, A.H.

    1985-01-01

    This paper describes a rapid and reliable method for quantification of damage to mitochondrial DNA (mtDNA), especially strand breaks. The degree of damage to mtDNA is assessed by the proportion of physical forms (i.e., supercoiled versus open-circular and linear forms) upon agarose gel electrophoresis, blotting, and visualization by hybridization with (/sup 32/P)mtDNA probes. The use of a radiolabeled probe is a crucial step in the procedure because it provides both a means to quantify by radioautography and to obtain the mtDNA specificity required to eliminate misinterpretation due to nuclear DNA contamination. To demonstrate the utility of this technique, X-irradiation and epichlorohydrin are shown to damage both isolated mtDNA and mtDNA in whole cells in a dose-dependent fashion.

  7. Measurement of lattice damage caused by ion-implantation doping of semiconductors.

    NASA Technical Reports Server (NTRS)

    Hunsperger, R. G.; Wolf, E. D.; Shifrin, G. A.; Marsh, O. J.; Jamba, D. M.

    1971-01-01

    Discussion of two new techniques used to measure the lattice damage produced in GaAs by the implantation of 60 keV cadmium ions. In the first method, optical reflection spectra of the ion-implanted samples were measured in the wavelength range from 2000 to 4600 A. The decrease in reflectivity resulting from ion-implantation was used to determine the relative amount of lattice damage as a function of ion dose. The second technique employed the scanning electron microscope. Patterns very similar in appearance to Kikuchi electron diffraction patterns are obtained when the secondary and/or backscattered electron intensity is displayed as a function of the angle of incidence of the electron beam on a single crystal surface. The results of measurements made by both methods are compared with each other and with data obtained by the method of measuring lattice damage by Rutherford scattering of 1 MeV helium ions.

  8. [Prevention and control of air pollution needs to strengthen further study on health damage caused by air pollution].

    PubMed

    Wu, T C

    2016-08-06

    Heath issues caused by air pollution such as particulate matter (PM) are much concerned and focused among air, water and soil pollutions because human breathe air for whole life span. Present comments will review physical and chemical characteristics of PM2.5 and PM10; Dose-response associations of PM10, PM2.5 and their components with mortality and risk of cardiopulmonary diseases, early health damages such as the decrease of lung functions and heart rate variability, DNA damage; And the roles of genetic variations and epigenetic changes in lung functions and heart rate variability, DNA damage related to PMs and their components. This comments list some limitations and perspectives about the associations of air pollution with health.

  9. Chronic Kidney Disease Is Characterized by “Double Trouble” Higher Pulse Pressure plus Night-Time Systolic Blood Pressure and More Severe Cardiac Damage

    PubMed Central

    Fedecostante, Massimiliano; Spannella, Francesco; Cola, Giovanna; Espinosa, Emma; Dessì-Fulgheri, Paolo; Sarzani, Riccardo

    2014-01-01

    Background Hypertension plays a key role in chronic kidney disease (CKD), but CKD itself affects the blood pressure (BP) profile. The aim of this study was to assess the association of BP profile with CKD and the presence of cardiac organ damage. Methods We studied 1805 patients, referred to our Hypertension Centre, in whom ABPM, blood tests, and echocardiography were clinically indicated. The glomerular filtration rate was estimated (eGFR) using the MDRD equation and CKD was defined as eGFR<60 mL/min/1.73 m2. Cardiac organ damage was evaluated by echocardiography. Results Among patients with CKD there were higher systolic blood pressure (SBP) during the night-time, greater prevalence of non-dippers (OR: 1.8) and increased pulse pressure (PP) during 24-hour period, daytime and night-time (all p<0.001). Patients with CKD had a greater LVM/h2.7 index, and a higher prevalence of left ventricular hypertrophy and diastolic dysfunction (all p<0.001). Nocturnal SBP and PP correlated more strongly with cardiac organ damage (p<0.001). Patients with CKD had a greater Treatment Intensity Score (p<0.001) in the absence of a significantly greater BP control. Conclusions CKD patients have an altered night-time pressure profile and higher PP that translate into a more severe cardiac organ damage. In spite of a greater intensity of treatment in most patients with CKD, BP control was similar to patients without CKD. Our findings indicate the need of a better antihypertensive therapy in CKD, better selected drugs, dosages and posology to provide optimal coverage of 24 hours and night-time BP. PMID:24465931

  10. Static-transmission-error vibratory-excitation contributions from plastically deformed gear teeth caused by tooth bending-fatigue damage

    NASA Astrophysics Data System (ADS)

    Mark, W. D.; Reagor, C. P.

    2007-02-01

    To assess gear health and detect gear-tooth damage, the vibratory response from meshing gear-pair excitations is commonly monitored by accelerometers. In an earlier paper, strong evidence was presented suggesting that, in the case of tooth bending-fatigue damage, the principal source of detectable damage is whole-tooth plastic deformation; i.e. yielding, rather than changes in tooth stiffness caused by tooth-root cracks. Such plastic deformations are geometric deviation contributions to the "static-transmission-error" (STE) vibratory excitation caused by meshing gear pairs. The STE contributions caused by two likely occurring forms of such plastic deformations on a single tooth are derived, and displayed in the time domain as a function of involute "roll distance." Example calculations are provided for transverse contact ratios of Qt=1.4 and 1.8, for spur gears and for helical-gear axial contact ratios ranging from Qa=1.2 to Qa=3.6. Low-pass- and band-pass-filtered versions of these same STE contributions also are computed and displayed in the time domain. Several calculations, consisting of superposition of the computed STE tooth-meshing fundamental harmonic contribution and the band-pass STE contribution caused by a plastically deformed tooth, exhibit the amplitude and frequency or phase modulation character commonly observed in accelerometer-response waveforms caused by damaged teeth. General formulas are provided that enable computation of these STE vibratory-excitation contributions for any form of plastic deformation on any number of teeth for spur and helical gears with any contact ratios.

  11. BDNF Regains Function in Hippocampal Long-Term Potentiation Deficits Caused by Diencephalic Damage

    ERIC Educational Resources Information Center

    Vedder, Lindsey C.; Savage, Lisa M.

    2017-01-01

    Thiamine deficiency (TD), commonly associated with chronic alcoholism, leads to diencephalic damage, hippocampal dysfunction, and spatial learning and memory deficits. We show a decrease in the magnitude of long-term potentiation (LTP) and paired-pulse facilitation (PPF) at CA3-CA1 synapses, independent of sex, following diencephalic damage…

  12. PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

    EPA Science Inventory

    PLASMID DNA DAMAGE CAOUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

    ABSTRACT

    Both dimethylarsinic acid (DMA(V)) and dimethylarsinous acid (DMA(III)) release iron from human liver ferritin (HLF) with or without the presence of ascorbic acid. ...

  13. Satellite detection of vegetative damage and alteration caused by pollutants emitted by a zinc smelter

    NASA Technical Reports Server (NTRS)

    Mcmurtry, G. J.; Petersen, G. W. (Principal Investigator); Fritz, E. L.; Pennypacker, S. P.

    1974-01-01

    The author has identified the following significant results. Field observations and data collected by low flying aircraft were used to verify the accuracy of maps produced from the satellite data. Although areas of vegetation as small as six acres can accurately be detected, a white pine stand that was severely damaged by sulfur dioxide could not be differentiated from a healthy white pine stand because spectral differences were not large enough. When winter data were used to eliminate interference from herbaceous and deciduous vegetation, the damage was still undetectable. The analysis was able to produce a character map that accurately delineated areas of vegetative alteration due to high zinc levels accumulating in the soil. The map depicted a distinct gradient of less damage and alteration as the distance from the smelter increased. Although the satellite data will probably not be useful for detecting small acreages of damaged vegetation, it is concluded that the data may be very useful as an inventory tool to detect and delineate large vegetative areas possessing differing spectral signatures.

  14. The psychosocial impact of the environmental damage caused by the MT Merapi eruption on survivors in Indonesia.

    PubMed

    Warsini, Sri; Buettner, Petra; Mills, Jane; West, Caryn; Usher, Kim

    2014-12-01

    The eruption of Indonesia's Mount Merapi volcano in 2010 caused extensive environmental degradation. Settlements and hundreds of hectares of farmlands were buried under volcanic ash. Until now, there has been no research on the psychosocial impact of living in an environment damaged by a volcanic eruption. We studied and compared the psychosocial impact of environmental damage on volcano survivors from two subdistricts-Cangkringan and Pakem. Cangkringan survivors affected by the 2010 eruption continue to live in a damaged environment. The Pakem subdistrict was damaged by eruptions of Mt Merapi in the 1990s but there is no recent damage to their environment. The Indonesian-Environmental Distress Scale (I-EDS), a translated revision of the original Environmental Distress Scale (EDS), was used to collect data. Exploratory statistical methods and multivariate linear regression analyses were performed to examine the relative contributions of demographic variables on the psychosocial impact of living in an environment damaged by volcanic eruption. A total of 348 survivors of the Mt Merapi eruption participated in the survey. The mean I-EDS score for Cangkringan district was 15.8 (SD 1.6; range 11.8-19.8) compared to 14.6 (SD 1.3; range 11.8-18.3) for Pakem district (P < 0.001). This result was confirmed by multiple linear regression analysis showing further that older respondents (P < 0.001), unemployed and retired respondents (P = 0.007), and respondents with no formal school education (P = 0.037) had lower I-EDS scores compared to the respective reference groups. Survivors of the Mt Merapi eruption who continue to live in the environment damaged by the 2010 volcanic eruption experience environmental distress. Relevant interventions should target those from low sosioeconomic groups to deal with the distress.

  15. Molecular mechanisms of silk gland damage caused by phoxim exposure and protection of phoxim-induced damage by cerium chloride in Bombyx mori.

    PubMed

    Li, Bing; Sun, Qingqing; Yu, Xiaohong; Xie, Yi; Hong, Jie; Zhao, Xiaoyang; Sang, Xuezi; Shen, Weide; Hong, Fashui

    2015-09-01

    It is known that exposure to organophosphorus pesticides (OP) including phoxim can produce oxidative stress, neurotoxicity, and greatly attenuate cocooning rate in the silkworm, Bombyx mori. Cerium treatment has been demonstrated to relieve phoxim-induced toxicity in B. mori; however, very little is known about the molecular mechanisms of silk gland injury due to OP exposure and protection of gland damage due to cerium pretreatment. The aim of this study was to evaluate silk gland damage and its molecular mechanisms in phoxim-induced silkworm toxicity and the protective mechanisms of cerium following exposure to phoxim. The results showed that phoxim exposure resulted in severe gland damage, reductions in protein synthesis and the cocooning rate of silkworms. Cerium (Ce) attenuated gland damage caused by phoxim, promoted protein synthesis, increased the antioxidant capacity of the gland and increased the cocooning rate of B. mori. Furthermore, digital gene expression data suggested that phoxim exposure led to significant up-regulation of 714 genes and down-regulation of 120 genes. Of these genes, 122 were related to protein metabolism, specifically, the down-regulated Ser2, Ser3, Fib-L, P25, and CYP450. Ce pretreatment resulted in up-regulation of 162 genes, and down-regulation of 141 genes, importantly, Ser2, Ser3, Fib-L, P25, and CYP333B8 were up-regulated. Treatment with CeCl3 + phoxim resulted in higher levels of Fib-L, P25, Ser2, Ser3, CAT, TPx, and CYP333B8 expression in the silk gland of silkworms. These findings indicated that Ce increased cocooning rate via the promotion of silk protein synthesis-related gene expression in the gland under phoxim-induced toxicity. These findings may expand the application of rare earths in sericulture.

  16. Genetic damage caused by methyl-parathion in mouse spermatozoa is related to oxidative stress

    SciTech Connect

    Pina-Guzman, B.; Solis-Heredia, M.J.; Rojas-Garcia, A.E.; Uriostegui-Acosta, M.; Quintanilla-Vega, B. . E-mail: mquintan@cinvestav.mx

    2006-10-15

    Organophosphorous (OP) pesticides are considered genotoxic mainly to somatic cells, but results are not conclusive. Few studies have reported OP alterations on sperm chromatin and DNA, and oxidative stress has been related to their toxicity. Sperm cells are very sensitive to oxidative damage which has been associated with reproductive dysfunctions. We evaluated the effects of methyl-parathion (Me-Pa; a widely used OP) on sperm DNA, exploring the sensitive stage(s) of spermatogenesis and the relationship with oxidative stress. Male mice (10-12-weeks old) were administered Me-Pa (3-20 mg/kg bw/i.p.) and euthanized at 7- or 28-days post-treatment. Mature spermatozoa were obtained and evaluated for chromatin structure through SCSA (Sperm Chromatin Structure Assay; DNA Fragmentation Index parameters: Mean DFI and DFI%) and chromomycin-A{sub 3} (CMA{sub 3})-staining, for DNA damage through in situ-nick translation (NT-positive) and for oxidative stress through lipid peroxidation (LPO; malondialdehyde production). At 7-days post-treatment (mature spermatozoa when Me-Pa exposure), dose-dependent alterations in chromatin structure (Mean DFI and CMA{sub 3}-staining) were observed, as well as increased DNA damage, from 2-5-fold in DFI% and NT-positive cells. Chromatin alterations and DNA damage were also observed at 28-days post-treatment (cells at meiosis at the time of exposure); suggesting that the damage induced in spermatocytes was not repaired. Positive correlations were observed between LPO and sperm DNA-related parameters. These data suggest that oxidative stress is related to Me-Pa alterations on sperm DNA integrity and cells at meiosis (28-days post-treatment) and epididymal maturation (7-days post-treatment) are Me-Pa targets. These findings suggest a potential risk of Me-Pa to the offspring after transmission.

  17. Tissue damage by laser radiation: an in vitro comparison between Tm:YAG and Ho:YAG laser on a porcine kidney model.

    PubMed

    Huusmann, Stephan; Wolters, Mathias; Kramer, Mario W; Bach, Thorsten; Teichmann, Heinrich-Otto; Eing, Andreas; Bardosi, Sebastian; Herrmann, Thomas R W

    2016-01-01

    The understanding of tissue damage by laser radiation is very important for the safety in the application of surgical lasers. The objective of this study is to evaluate cutting, vaporization and coagulation properties of the 2 µm Tm:YAG laser (LISA Laser Products OHG, GER) in comparison to the 2.1 µm Ho:YAG laser (Coherent Medical Group, USA) at different laser power settings in an in vitro model of freshly harvested porcine kidneys. Laser radiation of both laser generators was delivered by using a laser fiber with an optical core diameter of 550 µm (RigiFib, LISA Laser GER). Freshly harvested porcine kidneys were used as tissue model. Experiments were either performed in ambient air or in aqueous saline. The Tm:YAG laser was adjusted to 5 W for low and 120 W for the high power setting. The Ho:YAG laser was adjusted to 0.5 J and 10 Hz (5 W average power) for low power setting and to 2.0 J and 40 Hz (80 W average power) for high power setting, accordingly. The specimens of the cutting experiments were fixed in 4 % formalin, embedded in paraffin and stained with Toluidin blue. The laser damage zone was measured under microscope as the main evaluation criteria. Laser damage zone consists of an outer coagulation zone plus a further necrotic zone. In the ambient air experiments the laser damage zone for the low power setting was 745 ± 119 µm for the Tm:YAG and 614 ± 187 µm for the Ho:YAG laser. On the high power setting, the damage zone was 760 ± 167 µm for Tm:YAG and 715 ± 142 µm for Ho:YAG. The incision depth in ambient air on the low power setting was 346 ± 199 µm for Tm:YAG, 118 ± 119 µm for Ho:YAG. On the high power setting incision depth was 5083 ± 144 µm (Tm:YAG) and 1126 ± 383 µm (Ho:YAG) respectively. In the saline solution experiments, the laser damage zone was 550 ± 137 µm (Tm:YAG) versus 447 ± 65 µm (Ho:YAG), on the low power setting and 653 ± 137 µm (Tm:YAG) versus 677 ± 134 µm (Ho

  18. Kidney cancer.

    PubMed

    Linehan, W Marston; Rathmell, W Kimryn

    2012-01-01

    Over 65,000 Americans are diagnosed with kidney cancer each year and nearly 13,000 die of this disease. Kidney cancer is not a single disease, it is made up of a number of different types of cancer, each with a different histology, a different clinical course, responding differently to therapy and caused by a different gene. Study of the 13 genes that are known to cause kidney cancer has led to the understanding that kidney cancer is a metabolic disease. Recent discoveries of chromatin remodeling/histone modifying genes, such as PBRM1 and SETD2, have opened up new areas of intense interest in the study of the fundamental genetic basis of kidney cancer. New approaches to immunotherapy with agents such as the CTLA4 inhibitor, ipilumumab, have opened up promising new directions for clinical trials. A number of new agents targeting of VEGF receptor signaling and the mTOR pathways as well as novel approaches targeting HIF2 will hopefully provide the foundation for the development of effective forms of therapy for this disease.

  19. Early changes in scores of chronic damage on transplant kidney protocol biopsies reflect donor characteristics, but not future graft function.

    PubMed

    Caplin, Ben; Veighey, Kristin; Mahenderan, Arundathi; Manook, Miriam; Henry, Joanne; Nitsch, Dorothea; Harber, Mark; Dupont, Peter; Wheeler, David C; Jones, Gareth; Fernando, Bimbi; Howie, Alexander J; Veitch, Peter

    2013-01-01

    The amount of irreversible injury on renal allograft biopsy predicts function, but little is known about the early evolution of this damage. In a single-center cohort, we examined the relationship between donor-, recipient-, and transplantation-associated factors and change in a morphometric index of chronic damage (ICD) between protocol biopsies performed at implantation and at 2-3 months. We then investigated whether early delta ICD predicted subsequent biochemical outcomes. We found little evidence to support differences between the study group, who had undergone serial biopsies, and a contemporaneous control group, who had not. In allografts with serial biopsies (n = 162), there was an increase in ICD between implantation (median: 2%, IQR:0-8) and 2-3 months post-transplant (median 8% IQR:4-15; p < 0.0001). Donation from younger or live donors was independently associated with smaller early post-transplant increases in ICD. There was no evidence for a difference in delta ICD between donation after cardiac death vs. donation after brain death, nor association with length of cold ischemia. After adjustment for GFR at the time of the second biopsy, delta ICD after three months did not predict allograft function at one yr. These findings suggest that graft damage develops shortly after transplantation and reflects donor factors, but does not predict future biochemical outcomes.

  20. Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice.

    PubMed

    Ma, Wenqiang; Li, Shihua; Ma, Shuoqian; Jia, Lina; Zhang, Fuchun; Zhang, Yong; Zhang, Jingyuan; Wong, Gary; Zhang, Shanshan; Lu, Xuancheng; Liu, Mei; Yan, Jinghua; Li, Wei; Qin, Chuan; Han, Daishu; Qin, Chengfeng; Wang, Na; Li, Xiangdong; Gao, George Fu

    2016-12-01

    Zika virus (ZIKV) persists in the semen of male patients, a first for flavivirus infection. Here, we demonstrate that ZIKV can induce inflammation in the testis and epididymidis, but not in the prostate or seminal vesicle, and can lead to damaged testes after 60 days post-infection in mice. ZIKV induces innate immune responses in Leydig, Sertoli, and epididymal epithelial cells, resulting in the production of pro-inflammatory cytokines/chemokines. However, ZIKV does not induce a rapid and abundant cytokine production in peritubular cell and spermatogonia, suggesting that these cells are vulnerable for ZIKV infection and could be the potential repositories for ZIKV. Our study demonstrates a correlation between ZIKV and testis infection/damage and suggests that ZIKV infection, under certain circumstances, can eventually lead to male infertility.

  1. Nur77 forms novel nuclear structures upon DNA damage that cause transcriptional arrest

    SciTech Connect

    Leseleuc, Louis de; Denis, Francois . E-mail: francois.denis@iaf.inrs.ca

    2006-05-15

    The orphan nuclear receptor Nur77 has been implicated in both growth and apoptosis, and its function and activity can be modulated by cellular redistribution. Green fluorescent protein-tagged Nur77 was used to evaluate the role of Nur77 intracellular redistribution in response to genotoxic stress. Selected DNA damaging agents and transcription inhibition lead to rapid redistribution of Nur77 into nuclear structures distinct from conventional nuclear bodies. These nuclear bodies formed transiently were tightly bound to the nuclear matrix and conditions that lead to their appearance were associated with Nur77 transcriptional inhibition. The formation of Nur77 nuclear bodies might be involved in programmed cell death modulation upon exposure to DNA damaging agents that inhibit transcription by sequestrating this proapoptotic factor in dense nuclear structures.

  2. Chromosome Damage and Early Developmental Arrest Caused by the Rex Element of Drosophila Melanogaster

    PubMed Central

    Robbins, L. G.; Pimpinelli, S.

    1994-01-01

    Rex (Ribosomal exchange) is a genetically identified repeated element within the ribosomal DNA (rDNA) of Drosophila melanogaster. Rex has a semidominant maternal effect that promotes exchange between and within rDNA arrays in the first few embryonic mitoses. Several of Rex's genetic properties suggest that its primary effect is rDNA-specific chromosome breakage that is resolved by recombination. We report here that rDNA crossovers are only a small, surviving minority of Rex-induced events. Cytology of embryos produced by Rex-homozygous females reveals obvious chromosome damage in at least a quarter of the embryos within the first three mitotic divisions. More than half of the embryos produced by Rex females die, and the developmental arrest is among the earliest reported for any maternal-effect lethal. The striking lethal phenotype suggests that embryos with early chromosome damage could be particularly fruitful subjects for analysis of the cell biology of early embryos. PMID:7828823

  3. Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett's epithelial cells.

    PubMed

    Huo, Xiaofang; Juergens, Stefanie; Zhang, Xi; Rezaei, Davood; Yu, Chunhua; Strauch, Eric D; Wang, Jian-Ying; Cheng, Edaire; Meyer, Frank; Wang, David H; Zhang, Qiuyang; Spechler, Stuart J; Souza, Rhonda F

    2011-08-01

    Gastroesophageal reflux is associated with adenocarcinoma in Barrett's esophagus, but the incidence of this tumor is rising, despite widespread use of acid-suppressing medications. This suggests that refluxed material other than acid might contribute to carcinogenesis. We looked for potentially carcinogenetic effects of two bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on Barrett's epithelial cells in vitro and in vivo. We exposed Barrett's (BAR-T) cells to DCA or UDCA and studied the generation of reactive oxygen/nitrogen species (ROS/RNS); expression of phosphorylated H2AX (a marker of DNA damage), phosphorylated IkBα, and phosphorylated p65 (activated NF-κB pathway proteins); and apoptosis. During endoscopy in patients, we took biopsy specimens of Barrett's mucosa before and after esophageal perfusion with DCA or UDCA and assessed DNA damage and NF-κB activation. Exposure to DCA, but not UDCA, resulted in ROS/RNS production, DNA damage, and NF-κB activation but did not increase the rate of apoptosis in BAR-T cells. Pretreatment with N-acetyl-l-cysteine (a ROS scavenger) prevented DNA damage after DCA exposure, and DCA did induce apoptosis in cells treated with NF-κB inhibitors (BAY 11-7085 or AdIκB superrepressor). DNA damage and NF-κB activation were detected in biopsy specimens of Barrett's mucosa taken after esophageal perfusion with DCA, but not UDCA. These data show that, in Barrett's epithelial cells, DCA induces ROS/RNS production, which causes genotoxic injury, and simultaneously induces activation of the NF-κB pathway, which enables cells with DNA damage to resist apoptosis. We have demonstrated molecular mechanisms whereby bile reflux might contribute to carcinogenesis in Barrett's esophagus.

  4. Evaluation of skin damage caused by percutaneous absorption enhancers using fractal analysis.

    PubMed

    Obata, Y; Sesumi, T; Takayama, K; Isowa, K; Grosh, S; Wick, S; Sitz, R; Nagai, T

    2000-04-01

    Fractal analysis of the cross-sectional morphology of rat skin was conducted to evaluate pathologic changes evoked by percutaneous absorption enhancers. Male hairless rats (WBN/Ht-ILA), 8 weeks old, weighing 160 to 180 g were used. Under anesthetization, glass cells (10-mm inner diameter) were attached to the rats' abdomens, and test solutions containing various mixtures of the percutaneous absorption enhancers, sodium lauryl sulfate, isopropanol, 2-methyl-1-butanol, and sodium myristate were applied. Six hours after application, the solutions were removed and the abdominal skin was excised. Skin cross sections were analyzed with a charge-coupled device (CCD) camera. Image data taken by the CCD camera were fed into a desktop digital computer; then the fractal dimension of each skin cross section was determined on the basis of the box-counting algorithm. A pathologic study was also performed on the skin treated with the test solution. All sections of skin were examined with an optical photo microscope. Pathologic findings were classified into five levels. The total irritation score (TIS) was defined as the summation of damage levels in all regions. Only with the administration of hydrogel containing 2-methyl-1-butanol or sodium lauryl sulfate were positive values of TIS observed. However, the TIS values were independent of the concentration of these components. The most severe skin damage was evoked by application of sodium lauryl sulfate. Noticeable skin damage was also seen with 2-methyl-1-butanol. No irritation to the skin resulted from treatment with isopropanol or sodium myristate. When test solution containing sodium lauryl sulfate was applied to the skin, a remarkable increment in fractal dimensions was noted. This may suggest that the structure of the skin was greatly compromised as a result of sodium lauryl sulfate application. Although no change in fractal dimension was observed as a result of application of the test solution containing only 25

  5. Inhibition of root growth by narciclasine is caused by DNA damage-induced cell cycle arrest in lettuce seedlings.

    PubMed

    Hu, Yanfeng; Li, Jiaolong; Yang, Lijing; Nan, Wenbin; Cao, Xiaoping; Bi, Yurong

    2014-09-01

    Narciclasine (NCS) is an Amaryllidaceae alkaloid isolated from Narcissus tazetta bulbs. Its phytotoxic effects on plant growth were examined in lettuce (Lactuca sativa L.) seedlings. Results showed that high concentrations (0.5-5 μM) of NCS restricted the growth of lettuce roots in a dose-dependent manner. In NCS-treated lettuce seedlings, the following changes were detected: reduction of mitotic cells and cell elongation in the mature region, inhibition of proliferation of meristematic cells, and cell cycle. Moreover, comet assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay indicated that higher levels NCS (0.5-5 μM) induced DNA damage in root cells of lettuce. The decrease in meristematic cells and increase in DNA damage signals in lettuce roots in responses to NCS are in a dose-dependent manner. NCS-induced reactive oxygen species accumulation may explain an increase in DNA damage in lettuce roots. Thus, the restraint of root growth is due to cell cycle arrest which is caused by NCS-induced DNA damage. In addition, it was also found that NCS (0.5-5 μM) inhibited the root hair development of lettuce seedlings. Further investigations on the underlying mechanism revealed that both auxin and ethylene signaling pathways are involved in the response of root hairs to NCS.

  6. A disease-causing mutation illuminates the protein membrane topology of the kidney-expressed prohibitin homology (PHB) domain protein podocin.

    PubMed

    Schurek, Eva-Maria; Völker, Linus A; Tax, Judit; Lamkemeyer, Tobias; Rinschen, Markus M; Ungrue, Denise; Kratz, John E; Sirianant, Lalida; Kunzelmann, Karl; Chalfie, Martin; Schermer, Bernhard; Benzing, Thomas; Höhne, Martin

    2014-04-18

    Mutations in the NPHS2 gene are a major cause of steroid-resistant nephrotic syndrome, a severe human kidney disorder. The NPHS2 gene product podocin is a key component of the slit diaphragm cell junction at the kidney filtration barrier and part of a multiprotein-lipid supercomplex. A similar complex with the podocin ortholog MEC-2 is required for touch sensation in Caenorhabditis elegans. Although podocin and MEC-2 are membrane-associated proteins with a predicted hairpin-like structure and amino and carboxyl termini facing the cytoplasm, this membrane topology has not been convincingly confirmed. One particular mutation that causes kidney disease in humans (podocin(P118L)) has also been identified in C. elegans in genetic screens for touch insensitivity (MEC-2(P134S)). Here we show that both mutant proteins, in contrast to the wild-type variants, are N-glycosylated because of the fact that the mutant C termini project extracellularly. Podocin(P118L) and MEC-2(P134S) did not fractionate in detergent-resistant membrane domains. Moreover, mutant podocin failed to activate the ion channel TRPC6, which is part of the multiprotein-lipid supercomplex, indicative of the fact that cholesterol recruitment to the ion channels, an intrinsic function of both proteins, requires C termini facing the cytoplasmic leaflet of the plasma membrane. Taken together, this study demonstrates that the carboxyl terminus of podocin/MEC-2 has to be placed at the inner leaflet of the plasma membrane to mediate cholesterol binding and contribute to ion channel activity, a prerequisite for mechanosensation and the integrity of the kidney filtration barrier.

  7. Liver and kidney damage induced by 4-aminopyridine in a repeated dose (28 days) oral toxicity study in rats: gene expression profile of hybrid cell death.

    PubMed

    Frejo, María Teresa; Del Pino, Javier; Lobo, Margarita; García, Jimena; Capo, Miguel Andrés; Díaz, María Jesús

    2014-03-03

    4-Aminopyridine (4-AP) is an orphan drug indicated for the treatment of neuromuscular disorders. There is a great controversy around the use of this drug because of its narrow safety index and because a large number of adverse effects have been reported. Moreover, it was shown to induce cell death in different cell lines, being reported mainly apoptosis and necrosis as the principal pathways of cell death mediated by blockage of K channels or the Na, K-ATPase, but until now it was not described in vivo cell death induced by 4-aminipyridine. To provide new subchronic toxicity data and specifically, evaluate if 4-AP is able to induce in vivo cell death process and the main pathways related to it, a repeated dose (28 days) oral toxicity study, at therapeutic range of doses, was conducted in rats. The anatomical pathology, the biochemical and hematological parameters were analyzed and a real-time PCR array analysis was developed with an Ingenuity Pathway Analysis (IPA). The leucocytes number, the lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) enzymatic activity were increased at all dose but the erythrocytes number, the hemoglobin concentration, the alkaline phosphatase (FAL) and alanine aminotransferase (ALT) enzymatic activity were increased only at highest dose studied. However, glucose levels decreased at all doses. The biochemical results are indicative of hepatic damage. The anatomy pathology studies showed cell death only on liver and kidney, and the real-time PCR array on liver tissue expressed a gene expression profile of necrotic and apoptotic induced cell death. The present work shows for the first time in vivo cell death on liver and kidney with features of apoptosis and necrosis induced by 4-AP and the gene expression profile shows that the cell death is mediated by necrotic and apoptotic pathways that support this finding.

  8. Protective Effects of Selenium, Vitamin E, and Purple Carrot Anthocyanins on D-Galactose-Induced Oxidative Damage in Blood, Liver, Heart and Kidney Rats.

    PubMed

    Li, Xia; Zhang, Yunlong; Yuan, Yuan; Sun, Yong; Qin, Yan; Deng, Zeyuan; Li, Hongyan

    2016-10-01

    The present study was performed to investigate the protective effects of selenium (Se), vitamin E (Vit E) and anthocyanins from purple carrots and their combination against the oxidative stress induced by D-galactose in rats. A total of 80 male rats were equally divided into 11 groups, one of which acted as control (I) just receiving intraperitoneal injections of physiological saline. The remaining ten groups (II-XI) were intraperitoneally injected with D-galactose at a dose of 400 mg kg(-1) body weight (BW) per day for 42 consecutive days. Rats in groups III-XI were treated with antioxidants via gavage per day as follows: group III: Se-methylselenocysteine (SeMSC), IV: Se as sodium selenite (Na2SeO3), V: Se-enriched yeast (SeY), VI: Vit E as α-tocopherol acetate, VII: anthocyanin from purple carrots (APC), VIII: APC + Vit E, IX: SeMSC + APC+ Vit E, X: Na2SeO3 + APC + Vit E, XI: SeY + Ant + Vit E. The results showed that the rats treated with antioxidants (III-XI) showed significant decreases in the levels of malondialdehyde (MDA) and carbonyl protein (PCO) compared with the D-galactose-treated group (II) in the heart, liver, kidneys, and blood. Moreover, there were significant increases in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), glutathione (GSH) concentration, and total antioxidant capacity (T-AOC) in the heart, liver, kidneys, and blood of antioxidant-treated animals (III-XI) than those in control group (I). In addition, the combined treatments of two or three antioxidants showed greater antioxidant activities than those of individual treatments, suggesting the synergistic antioxidant effects of Se, Vit E, and APC. In conclusion, all the antioxidants exhibited protective effects against D-galactose-induced oxidative damage in rats, and these antioxidants showed a synergistic effect.

  9. The prevention of ischemia/reperfusion induced oxidative damage by venous blood in rabbit kidneys monitored with biochemical, histopatological and immunohistochemical analysis.

    PubMed

    Cetin, N; Suleyman, H; Sener, E; Demirci, E; Gundogdu, C; Akcay, F

    2014-06-01

    The purpose of this study was to investigate the biochemical, histopathological and immunohistochemical effects of venous blood on ischemia/reperfusion-induced oxidative DNA damage and mutation in rabbit kidneys in comparison to melatonin treatment, which has a known protective effect against ischemia/reperfusion (IR) injury. The rabbits were divided into five groups: renal ischemia (RI), renal ischemia-reperfusion (RIR), renal ischemia-venous blood-reperfusion (RIVR), melatonin + renal ischemia-reperfusion (MRIR), and the healthy sham control group (HG). Melatonin (2.5 mg/kg delivered intraperitoneally) was administered one hour prior to ischemia. In the RIVR group, 1 ml of venous blood was administered 5 minutes before the reperfusion. The xanthine oxidase activity in the kidney tissue was determined as 53.50 ± 1.72, 31.00 ± 6.39, 45.66 ± 9.20, 28.66 ± 6.05 and 14.33 ± 1.28 U/g protein; the MDA levels were 6.32 ± 0.02, 19.50 ± 1.33, 7.00 ± 0.96, 7.50 ± 0.76 and 4.75 ± 0.34 mmol/g protein; and the GSH levels were 4.50 ± 1.08, 2.76 ± 0.13, 5.48 ± 0.22, 4.93 ± 0.55 and 6.98 ± 0.33 nmol/g protein in the RI, RIR, RIVR, MRIR and HG groups, respectively. Blood, blood urea nitrogen (BUN) and creatinine levels were classified as high only in the RIR group. The MRIR and RIVR groups, in which oxidative stress was best suppressed, had much milder histopathological and immunohistochemical findings compared to the RIR group. This study has revealed that it is useful to initiate reperfusion of the ischemic tissue with venous blood.

  10. [Methylmercury causes diffuse damage to the somatosensory cortex: how to diagnose Minamata disease].

    PubMed

    Ekino, Shigeo; Ninomiya, Tadashi; Imamura, Keiko; Susa, Mari

    2007-01-01

    The first acute case of methylmercury (MeHg) poisoning by the consumption of fish arose in Minamata, Japan, in 1953. It was officially recognized and called Minamata disease (MD) in 1956. There are still arguments about the definition of MD in terms of its associated clinical symptoms and lesions even 50 years after the initial recognition of MD. Studies on this MD epidemic are reviewed along with its historical background. Since MeHg dispersed from Minamata to the Shiranui Sea, residents living around the sea had been exposed to low-dose MeHg through fish consumption for about 20 years (at least from 1950 to 1968). These chronic MeHg poisoning patients complained of paresthesia at the distal parts of their extremities and around the lips even 30 years after the cessation of exposure to MeHg of anthropogenic origin. The persisting somatosensory disorders after the discontinuation of exposure to MeHg were induced by diffuse damage to the somatosensory cortex, but not by damage to the peripheral nervous system, as previously believed. Based on these findings, symptoms and lesions in MeHg poisoning are reappraised.

  11. Depletion of Mitofusin-2 Causes Mitochondrial Damage in Cisplatin-Induced Neuropathy.

    PubMed

    Bobylev, Ilja; Joshi, Abhijeet R; Barham, Mohammed; Neiss, Wolfram F; Lehmann, Helmar C

    2017-01-21

    Sensory neuropathy is a relevant side effect of the antineoplastic agent cisplatin. Mitochondrial damage is assumed to play a critical role in cisplatin-induced peripheral neuropathy, but the pathomechanisms underlying cisplatin-induced mitotoxicity and neurodegeneration are incompletely understood. In an animal model of cisplatin-induced neuropathy, we determined in detail the extent and spatial distribution of mitochondrial damage during cisplatin treatment. Changes in the total number of axonal mitochondria during cisplatin treatment were assessed in intercostal nerves from transgenic mice that express cyan fluorescent protein. Further, we explored the impact of cisplatin on the expression of nuclear encoded molecules of mitochondrial fusion and fission, including mitofusin-2 (MFN2), optic atrophy 1 (OPA1), and dynamin-related protein 1 (DRP1). Cisplatin treatment resulted in a loss of total mitochondrial mass in axons and in an abnormal mitochondrial morphology including atypical enlargement, increased vacuolization, and loss of cristae. These changes were observed in distal and proximal nerve segments and were more prominent in axons than in Schwann cells. Transcripts of fusion and fission proteins were reduced in distal nerve segments. Significant reduced expression levels of the fusion protein MFN2 was detected in nerves of cisplatin-exposed animals. In summary, we provide for the first time an evidence that cisplatin alters mitochondrial dynamics in peripheral nerves. Loss of MFN2, previously implicated in the pathogenesis of other neurodegenerative diseases, also contributes to the pathogenesis in cisplatin-induced neuropathy.

  12. Genetic parameters for both a liver damage phenotype caused by and antibody response to phenotype in dairy and beef cattle.

    PubMed

    Twomey, A J; Sayers, R G; Carroll, R I; Byrne, N; Brien, E O'; Doherty, M L; McClure, J C; Graham, D A; Berry, D P

    2016-10-01

    is a helminth parasite of economic importance to the global cattle industry, with documented high international herd prevalence. The objective of the present study was to generate the first published genetic parameter estimates for liver damage caused by as well as antibody response to in cattle. Abattoir data on the presence of live , or -damaged livers, were available between the years 2012 and 2015, inclusive. A second data set was available on cows from 68 selected dairy herds with a blood ELISA test for antibody response to in autumn 2015. Animals were identified as exposed by using herd mate phenotype, and only exposed animals were retained for analysis. The abattoir data set consisted of 20,481 dairy cows and 75,041 young dairy and beef animals, whereas the study herd data set consisted of 6,912 dairy cows. (Co)variance components for phenotypes in both data sets were estimated using animal linear mixed models. Fixed effects included in the model for both data sets were contemporary group, heterosis coefficient, recombination loss coefficient, parity, age relative to parity/age group, and stage of lactation. An additional fixed effect of abattoir by date of slaughter was included in the model for the analysis of the abattoir data. Direct additive genetic effects and a residual effect were included as random effects for all analyses. After data edits, the prevalence of liver damage caused by in cows and young cattle was 47% and 20%, respectively. The prevalence of a positive antibody response to in cows from the study herd data was 36% after data edits. The heritability of as a binary trait for dairy cows in abattoir data and study herd data was 0.03 ± 0.01 and 0.09 ± 0.02, respectively; heritability in young cattle was 0.01 ± 0.005. The additive genetic SD of as a binary trait was 0.069 and 0.050 for cows and young cattle from the abattoir data, respectively, and 0.112 from the study herd cows. The genetic correlation between liver damage caused by in

  13. {beta}-carboline derivatives: Novel photosensitizers that intercalate into DNA to cause direct DNA damage in photodynamic therapy

    SciTech Connect

    Guan Huaji; Liu Xiaodong; Peng Wenlie; Cao Rihui; Ma Yan; Chen Hongsheng; Xu Anlong . E-mail: ls36@zsu.edu.cn

    2006-04-14

    Novel 1,3,9-trisubstituted {beta}-carboline derivatives were found to exhibit DNA photocleavage properties under visible light irradiation in a cell-free system, which could be reduced by antioxidant vitamin E. Their photo-cytotoxicity to human tumor cell line HeLa was confirmed, in which apoptosis only contributed a small part to the cell death, and necrosis was the dominating outcome of HeLa cells in photodynamic therapy (PDT) using {beta}-carboline derivatives. Different from other clinical PDT drugs, {beta}-carboline derivatives were demonstrated to be able to distribute in the nucleus and intercalate into DNA, and consequently cause direct DNA damage by photochemical reaction products in PDT, which was proved by the distinct DNA tails in the comet assay and the considerable amount of DNA damaged cells quantified by flow cytometry. This mechanism could be the explanation for the delay of cell proliferation at DNA synthesis and mitosis.

  14. Angular absorption of light used for evaluation of structural damage to porcine meat caused by aging, drying and freezing.

    PubMed

    Kaspar, Pavel; Prokopyeva, Elena; Tománek, Pavel; Grmela, Lubomír

    2017-04-01

    Meat as a rich source of protein is sought after by people from all over the world. It is also very susceptible to decay because of many internal and external processes affecting it. In this work an easy and quick method of detection of structural damage caused by decay or mishandling the meat is attempted by the method of angular absorption of light. The difference between structural changes due to aging, drying and freezing is explored and the resulting changes in light absorption in meat samples are presented. This work demonstrates that the measurement of optical angular dependency of absorption in relation to the muscle fibers in muscle tissue has the potential of detecting structural damage to the sample for meat quality control purposes.

  15. 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

  16. DNA damage and apoptosis of endometrial cells cause loss of the early embryo in mice exposed to carbon disulfide

    SciTech Connect

    Zhang, Bingzhen; Shen, Chunzi; Yang, Liu; Li, Chunhui; Yi, Anji; Wang, Zhiping

    2013-12-01

    Carbon disulfide (CS{sub 2}) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS{sub 2} via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD{sub 50} (157.85 mg/kg), 0.2 LD{sub 50} (315.7 mg/kg) and 0.4 LD{sub 50} (631.4 mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showed definite dose–response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS{sub 2}. - Highlights: • We built an animal model of CS2 exposure during blastocyst implantation. • Endometrial cells were used in the comet assay to detect DNA damage. • CS2 exposure caused DNA damage and endometrial cell apoptosis. • DNA damage and endometrial cell apoptosis were responsible for embryo loss.

  17. Intermittent ethanol exposure induces inflammatory brain damage and causes long-term behavioural alterations in adolescent rats.

    PubMed

    Pascual, Maria; Blanco, Ana M; Cauli, Omar; Miñarro, Jose; Guerri, Consuelo

    2007-01-01

    Adolescent brain development seems to be important for the maturation of brain structures and behaviour. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage. Because we have demonstrated that chronic ethanol treatment induces inflammatory processes in the brain, we investigate whether intermittent ethanol intoxication enhances cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in adolescent rats, and whether these mediators induce brain damage and cause permanent cognitive dysfunctions. Adolescent rats were exposed to ethanol (3.0 g/kg) for two consecutive days at 48-h intervals over 14 days. Levels of COX-2, iNOS and cell death were assessed in the neocortex, hippocampus and cerebellum 24 h after the final ethanol administration. The following day or 20 days after the final injection (adult stage), animals were tested for different behavioural tests (conditional discrimination learning, rotarod, object recognition, beam-walking performance) to assess cognitive and motor functions. Our results show that intermittent ethanol intoxication upregulates COX-2 and iNOS levels, and increases cell death in the neocortex, hippocampus and cerebellum. Furthermore, animals treated with ethanol during adolescence exhibited behavioural deficits that were evident at the end of ethanol treatments and at the adult stage. Administration of indomethacin, a COX-2 inhibitor, abolishes the induction of COX-2 and iNOS expression and cell death, preventing ethanol-induced behavioural deficits. These findings indicate that binge pattern exposure to ethanol during adolescence induces brain damage by inflammatory processes and causes long-lasting neurobehavioural consequences. Accordingly, administering indomethacin protects against ethanol-induced brain damage and prevents detrimental ethanol effects on cognitive and motor processes.

  18. Glucantime® causes oxidative stress-derived DNA damage in Balb/c mice infected by Leishmania (Leishmania) infantum.

    PubMed

    Moreira, Vanessa Ribeiro; de Jesus, Luís Cláudio Lima; Soares, Rossy-Eric Pereira; Silva, Luis Douglas Miranda; Pinto, Bruno Araújo Serra; Melo, Maria Norma; Paes, Antonio Marcus de Andrade; Pereira, Silma Regina Ferreira

    2017-03-20

    Leishmaniasis is a neglected tropical disease caused by over 20 species of the protozoan parasite Leishmania Regarding treatment, Glucantime® is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effetcs, remain unclear. Therefore, the mechanism by which Glucantime® causes DNA damage was investigated in BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Glucantime® (20 mg/kg for 20 days). DNA damage was carried out by comet assay using mice leukocytes. Furthermore, comet assays followed by Formamidopyrimidine-DNA-glicosilase and Endonuclease III were performed, which remove oxidized DNA bases. In addition, the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were also assessed in the animals serum. To investigate mutagenicity, we carried out micronucleus test. Our data demonstrate that Glucantime® as well as Leishmania (Leishmania) infantum infection induce DNA damage in mammalian cell by oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, either Glucantime® treatment as well as Leishmania (Leishmania) infantum infection promote oxidative stress-derived DNA damage, which promoted overactivation of the SOD-CAT axis, whereas SOD-GPx axis was inhibited as a probable consequence of GSH depletion. Finally, our data still enable us to suggest that Glucantime® regimen, as recommended by World Health Organization, would compromise GPx activity leading to saturation of antioxidant defense systems that use thiol groups and might be harmful to patients under treatment.

  19. On the inlet vortex system. [preventing jet engine damage caused by debris pick-up

    NASA Technical Reports Server (NTRS)

    Bissinger, N. C.; Braun, G. W.

    1974-01-01

    The flow field of a jet engine with an inlet vortex, which can pick up heavy debris from the ground and damage the engine, was simulated in a small water tunnel by means of the hydrogen bubble technique. It was found that the known engine inlet vortex is accompained by a vortex system, consisting of two inlet vortices (the ground based and the trailing one), secondary vortices, and ground vortices. Simulation of the ground effect by an inlet image proved that the inlet vortex feeds on free stream vorticity and can exist without the presence of a ground boundary layer. The structural form of the inlet vortex system was explained by a simple potential flow model, which showed the number, location, and the importance of the stagnation points. A retractable horizontal screen or an up-tilt of the engine is suggested as countermeasure against debris ingestion.

  20. Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency.

    PubMed

    Griffith, Ann V; Venables, Thomas; Shi, Jianjun; Farr, Andrew; van Remmen, Holly; Szweda, Luke; Fallahi, Mohammad; Rabinovitch, Peter; Petrie, Howard T

    2015-08-18

    T lymphocytes are essential mediators of immunity that are produced by the thymus in proportion to its size. The thymus atrophies rapidly with age, resulting in progressive diminution of new T cell production. This decreased output is compensated by duplication of existing T cells, but it results in gradual dominance by memory T cells and decreased ability to respond to new pathogens or vaccines. Here, we show that accelerated and irreversible thymic atrophy results from stromal deficiency in the reducing enzyme catalase, leading to increased damage by hydrogen peroxide generated by aerobic metabolism. Genetic complementation of catalase in stromal cells diminished atrophy, as did chemical antioxidants, thus providing a mechanistic link between antioxidants, metabolism, and normal immune function. We propose that irreversible thymic atrophy represents a conventional aging process that is accelerated by stromal catalase deficiency in the context of an intensely anabolic (lymphoid) environment.

  1. Histone H3 K56 Hyperacetylation Perturbs Replisomes and Causes DNA Damage

    PubMed Central

    Celic, Ivana; Verreault, Alain; Boeke, Jef D.

    2008-01-01

    Deacetylation of histone H3 K56, regulated by the sirtuins Hst3p and Hst4p, is critical for maintenance of genomic stability. However, the physiological consequences of a lack of H3 K56 deacetylation are poorly understood. Here we show that cells lacking Hst3p and Hst4p, in which H3 K56 is constitutively hyperacetylated, exhibit hallmarks of spontaneous DNA damage, such as activation of the checkpoint kinase Rad53p and upregulation of DNA-damage inducible genes. Consistently, hst3 hst4 cells display synthetic lethality interactions with mutations that cripple genes involved in DNA replication and DNA double-strand break (DSB) repair. In most cases, synthetic lethality depends upon hyperacetylation of H3 K56 because it can be suppressed by mutation of K56 to arginine, which mimics the nonacetylated state. We also show that hst3 hst4 phenotypes can be suppressed by overexpression of the PCNA clamp loader large subunit, Rfc1p, and by inactivation of the alternative clamp loaders CTF18, RAD24, and ELG1. Loss of CTF4, encoding a replisome component involved in sister chromatid cohesion, also suppresses hst3 hst4 phenotypes. Genetic analysis suggests that CTF4 is a part of the K56 acetylation pathway that converges on and modulates replisome function. This pathway represents an important mechanism for maintenance of genomic stability and depends upon proper regulation of H3 K56 acetylation by Hst3p and Hst4p. Our data also suggest the existence of a precarious balance between Rfc1p and the other RFC complexes and that the nonreplicative forms of RFC are strongly deleterious to cells that have genomewide and constitutive H3 K56 hyperacetylation. PMID:18579506

  2. Displacement damage caused by gamma-rays and neutrons on Au and Se.

    SciTech Connect

    Doyle, Barney Lee

    2014-11-01

    This report documents theoretical calculations of displacement damage produced by gamma rays and neutrons on various materials. The average energy of the gamma rays was 1.24 MeV and 1.0 MeV for the neutrons. The fluence of the gamma rays was 1.2e14 γ/cm2 , for the neutrons it was 1.0e12 n/cm2. The initial materials of interest were Au and Se. The total doses of the gamma ray exposures were in the 100 kRad range for both elements. An equivalent electron fluence was approximated to be the same as the gamma ray fluence over one gamma ray attenuation length in both materials and at the same 1.24 MeV energy. The maximum recoil energy of the Au and Se for these electrons was calculated relativisticaly to be 29 and 72 eV respectively. The relativisitic McKinley and Feshbach theory for the atomic recoil cross sections produced by the electrons were in the 10s of mbarn range and an upper limit for the concentration of Frenkel pairs for the gamma ray exposures for both elements was in the ppb range. The Robinson Energy Partioning Theory for non-ionizing energy loss (NIEL) of ions in solids was used to calculate the concentration of Frenkel pairs produced by the 1 MeV neutrons, and this concentration was also in the ppb range for both Au and Se. Low damage levels like this can have effects on minority carrier recombination in semiconductors, but are not expected to have any effect on metals like Au, or metalloids such as Se.

  3. UV-B exposure causes DNA damage and changes in protein expression in northern pike (Esox lucius) posthatched embryos.

    PubMed

    Vehniäinen, Eeva-Riikka; Vähäkangas, Kirsi; Oikari, Aimo

    2012-01-01

    The ongoing anthropogenically caused ozone depletion and climate change has increased the amount of biologically harmful UV-B radiation, which is detrimental to fish in embryonal stages. The effects of UV-B radiation on the levels and locations of DNA damage manifested as cyclobutane pyrimidine dimers (CPDs), heat shock protein 70 (HSP70) and p53 protein in newly hatched embryos of pike were examined. Pike larvae were exposed in the laboratory to current and enhanced doses of UV-B radiation. UV-B exposure caused the formation of CPDs in a fluence rate-dependent manner, and the CPDs were found deeper in the tissues with increasing fluence rates. UV-B radiation induced HSP70 in epidermis, and caused plausible p53 activation in the brain and epidermis of some individuals. Also at a fluence rate occurring in nature, the DNA damage in the brain and eyes of pike and changes in protein expression were followed by severe behavioral disorders, suggesting that neural molecular changes were associated with functional consequences.

  4. Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease.

    PubMed

    Piccoli, Giorgina B; Grassi, Giorgio; Cabiddu, Gianfranca; Nazha, Marta; Roggero, Simona; Capizzi, Irene; De Pascale, Agostino; Priola, Adriano M; Di Vico, Cristina; Maxia, Stefania; Loi, Valentina; Asunis, Anna M; Pani, Antonello; Veltri, Andrea

    2015-01-01

    The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients.

  5. Kidney Diseases

    MedlinePlus

    ... Infections Your doctor can do blood and urine tests to check if you have kidney disease. If your kidneys fail, you will need dialysis or a kidney transplant. NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  6. Kidney Failure

    MedlinePlus

    ... upcoming screening events. Kidney Action Day Kidney Action Day Learn about our signature outreach event. About AKF ... support of AKF. Kidney Action Day Kidney Action Day Learn about our signature outreach event. Free health ...

  7. Kidney Transplant

    MedlinePlus

    Kidney transplant Overview By Mayo Clinic Staff A kidney transplant is a surgical procedure to place a healthy kidney ... bloodstream via a machine (dialysis) or a kidney transplant to stay alive. Mayo Clinic's approach . Mayo Clinic ...

  8. Kidney Disease

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Kidney Disease KidsHealth > For Teens > Kidney Disease Print A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...

  9. Kidney Disease

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Kidney Disease KidsHealth > For Teens > Kidney Disease A A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...

  10. Your Kidneys

    MedlinePlus

    ... Room? What Happens in the Operating Room? Your Kidneys KidsHealth > For Kids > Your Kidneys A A A ... and it will be lighter. What Else Do Kidneys Do? Kidneys are always busy. Besides filtering the ...

  11. Whole-body proton irradiation causes long-term damage to hematopoietic stem cells in mice.

    PubMed

    Chang, Jianhui; Feng, Wei; Wang, Yingying; Luo, Yi; Allen, Antiño R; Koturbash, Igor; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2015-02-01

    Space flight poses certain health risks to astronauts, including exposure to space radiation, with protons accounting for more than 80% of deep-space radiation. Proton radiation is also now being used with increasing frequency in the clinical setting to treat cancer. For these reasons, there is an urgent need to better understand the biological effects of proton radiation on the body. Such improved understanding could also lead to more accurate assessment of the potential health risks of proton radiation, as well as the development of improved strategies to prevent and mitigate its adverse effects. Previous studies have shown that exposure to low doses of protons is detrimental to mature leukocyte populations in peripheral blood, however, the underlying mechanisms are not known. Some of these detriments may be attributable to damage to hematopoietic stem cells (HSCs) that have the ability to self-renew, proliferate and differentiate into different lineages of blood cells through hematopoietic progenitor cells (HPCs). The goal of this study was to investigate the long-term effects of low-dose proton irradiation on HSCs. We exposed C57BL/6J mice to 1.0 Gy whole-body proton irradiation (150 MeV) and then studied the effects of proton radiation on HSCs and HPCs in the bone marrow (BM) 22 weeks after the exposure. The results showed that mice exposed to 1.0 Gy whole-body proton irradiation had a significant and persistent reduction of BM HSCs compared to unirradiated controls. In contrast, no significant changes were observed in BM HPCs after proton irradiation. Furthermore, irradiated HSCs and their progeny exhibited a significant impairment in clonogenic function, as revealed by the cobblestone area-forming cell (CAFC) and colony-forming cell assays, respectively. These long-term effects of proton irradiation on HSCs may be attributable to the induction of chronic oxidative stress in HSCs, because HSCs from irradiated mice exhibited a significant increase in NADPH

  12. Whole-Body Proton Irradiation Causes Long-Term Damage to Hematopoietic Stem Cells in Mice

    PubMed Central

    Chang, Jianhui; Feng, Wei; Wang, Yingying; Luo, Yi; Allen, Antiño R.; Koturbash, Igor; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    Space flight poses certain health risks to astronauts, including exposure to space radiation, with protons accounting for more than 80% of deep-space radiation. Proton radiation is also now being used with increasing frequency in the clinical setting to treat cancer. For these reasons, there is an urgent need to better understand the biological effects of proton radiation on the body. Such improved understanding could also lead to more accurate assessment of the potential health risks of proton radiation, as well as the development of improved strategies to prevent and mitigate its adverse effects. Previous studies have shown that exposure to low doses of protons is detrimental to mature leukocyte populations in peripheral blood, however, the underlying mechanisms are not known. Some of these detriments may be attributable to damage to hematopoietic stem cells (HSCs) that have the ability to self-renew, proliferate and differentiate into different lineages of blood cells through hematopoietic progenitor cells (HPCs). The goal of this study was to investigate the long-term effects of low-dose proton irradiation on HSCs. We exposed C57BL/6J mice to 1.0 Gy whole-body proton irradiation (150 MeV) and then studied the effects of proton radiation on HSCs and HPCs in the bone marrow (BM) 22 weeks after the exposure. The results showed that mice exposed to 1.0 Gy whole-body proton irradiation had a significant and persistent reduction of BM HSCs compared to unirradiated controls. In contrast, no significant changes were observed in BM HPCs after proton irradiation. Furthermore, irradiated HSCs and their progeny exhibited a significant impairment in clonogenic function, as revealed by the cobblestone area-forming cell (CAFC) and colony-forming cell assays, respectively. These long-term effects of proton irradiation on HSCs may be attributable to the induction of chronic oxidative stress in HSCs, because HSCs from irradiated mice exhibited a significant increase in NADPH

  13. Surgical management of a large peritoneal pseudocyst causing acute kidney injury secondary to abdominal compartment syndrome in a rare case of congenital absence of omentum during pregnancy.

    PubMed

    Jones, Benjamin P; Hunjan, Tia; Terry, Jayne

    2016-09-01

    Complete congenital absence of the omentum is very rare with only one previously reported case. We present a unique case of the management of a pregnant woman with a large pelvic pseudocyst caused by complications related to congenital absence of omentum, resulting in acute kidney injury, likely secondary to acute compartment syndrome. This case highlights the importance of considering acute compartment syndrome in critically unwell pregnant women and reiterates the need to measure intra-abdominal pressure when clinically indicated. Given that pregnancy is in itself a state of intra-abdominal hypertension, obstetricians should maintain a high index of suspicion in the context of additional risk factors.

  14. Splicing defects caused by exonic mutations in PKD1 as a new mechanism of pathogenesis in autosomal dominant polycystic kidney disease.

    PubMed

    Claverie-Martin, Felix; Gonzalez-Paredes, Francisco J; Ramos-Trujillo, Elena

    2015-01-01

    The correct splicing of precursor-mRNA depends on the actual splice sites plus exonic and intronic regulatory elements recognized by the splicing machinery. Surprisingly, an increasing number of examples reveal that exonic mutations disrupt the binding of splicing factors to these sequences or generate new splice sites or regulatory elements, causing disease. This contradicts the general assumption that missense mutations disrupt protein function and that synonymous mutations are merely polymorphisms. Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder caused mainly by mutations in the PKD1 gene. Recently, we analyzed a substantial number of PKD1 missense or synonymous mutations to further characterize their consequences on pre-mRNA splicing. Our results showed that one missense and 2 synonymous mutations induce significant defects in pre-mRNA splicing. Thus, it appears that aberrant splicing as a result of exonic mutations is a previously unrecognized cause of ADPKD.

  15. DNA polymerase III requirement for repair of DNA damage caused by methyl methanesulfonate and hydrogen peroxide

    SciTech Connect

    Hagensee, M.E.; Bryan, S.K.; Moses, R.E.

    1987-10-01

    The pcbA1 mutation allows DNA replication dependent on DNA polymerase I at the restrictive temperature in polC(Ts) strains. Cells which carry pcbA1, a functional DNA polymerase I, and a temperature-sensitive DNA polymerase III gene were used to study the role of DNA polymerase III in DNA repair. At the restrictive temperature for DNA polymerase III, these strains were more sensitive to the alkylating agent methyl methanesulfonate (MMS) and hydrogen peroxide than normal cells. The same strains showed no increase in sensitivity to bleomycin, UV light, or psoralen at the restrictive temperature. The sensitivity of these strains to MMS and hydrogen peroxide was not due to the pcbAl allele, and normal sensitivity was restored by the introduction of a chromosomal or cloned DNA polymerase III gene, verifying that the sensitivity was due to loss of DNA polymerase III alpha-subunit activity. A functional DNA polymerase III is required for the reformation of high-molecular-weight DNA after treatment of cells with MMS or hydrogen peroxide, as demonstrated by alkaline sucrose sedimentation results. Thus, it appears that a functional DNA polymerase III is required for the optimal repair of DNA damage by MMS or hydrogen peroxide.

  16. Environmental stress causes oxidative damage to plant mitochondria leading to inhibition of glycine decarboxylase.

    PubMed

    Taylor, Nicolas L; Day, David A; Millar, A Harvey

    2002-11-08

    A cytotoxic product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), rapidly inhibited glycine, malate/pyruvate, and 2-oxoglutarate-dependent O2 consumption by pea leaf mitochondria. Dose- and time-dependence of inhibition showed that glycine oxidation was the most severely affected with a K(0.5) of 30 microm. Several mitochondrial proteins containing lipoic acid moieties differentially lost their reactivity to a lipoic acid antibody following HNE treatment. The most dramatic loss of antigenicity was seen with the 17-kDa glycine decarboxylase complex (GDC) H-protein, which was correlated with the loss of glycine-dependent O2 consumption. Paraquat treatment of pea seedlings induced lipid peroxidation, which resulted in the rapid loss of glycine-dependent respiration and loss of H-protein reactivity with lipoic acid antibodies. Pea plants exposed to chilling and water deficit responded similarly. In contrast, the damage to other lipoic acid-containing mitochondrial enzymes was minor under these conditions. The implication of the acute sensitivity of glycine decarboxylase complex H-protein to lipid peroxidation products is discussed in the context of photorespiration and potential repair mechanisms in plant mitochondria.

  17. Repeated subrupture overload causes progression of nanoscaled discrete plasticity damage in tendon collagen fibrils.

    PubMed

    Veres, Samuel P; Harrison, Julia M; Lee, J Michael

    2013-05-01

    A critical feature of tendons and ligaments is their ability to resist rupture when overloaded, resulting in strains or sprains instead of ruptures. To treat these injuries more effectively, it is necessary to understand how overload affects the primary load-bearing elements of these tissues: collagen fibrils. We have investigated how repeated subrupture overload alters the collagen of tendons at the nanoscale. Using scanning electron microscopy to examine fibril morphology and hydrothermal isometric tension testing to look at molecular stability, we demonstrated that tendon collagen undergoes a progressive cascade of discrete plasticity damage when repeatedly overloaded. With successive overload cycles, fibrils develop an increasing number of kinks along their length. These kinks-discrete zones of plastic deformation known to contain denatured collagen molecules-are accompanied by a progressive and eventual total loss of D-banding along the surface of fibrils, indicating a loss of native molecular packing and further molecular denaturation. Thermal analysis of molecular stability showed that the destabilization of collagen molecules within fibrils is strongly related to the amount of strain energy dissipated by the tendon after yielding during tensile overload. These novel findings raise new questions about load transmission within tendons and their fibrils and about the interplay between crosslinking, strain-energy dissipation ability, and molecular denaturation within these structures.

  18. Water pollution causes ultrastructural and functional damages in Pellia neesiana (Gottsche) Limpr.

    PubMed

    Basile, Adriana; Sorbo, Sergio; Lentini, Marco; Conte, Barbara; Esposito, Sergio

    2016-11-25

    The aim of this work is to evaluate the effects of freshwater pollution in the heavily contaminated Sarno River (Campania, South Italy), using Pellia neesiana (Pelliaceae Metzgeriales) in order to propose this liverwort as a potential bioindicator, able to record the effects of water pollution, particularly the one related to metal (loid) contamination. Samples of P. neesiana in nylon bags were disposed floating for one week on the waters of Sarno River in three sites characterised by an increasing pollution. As control, some specimens were cultured in vitro in Cd- and Pb-added media, at the same pollutants' levels as measured in the most polluted site. P. neesiana cell ultrastructure was modified and severe alterations were observed in chloroplasts from samples exposed in the most polluted site, and Cd- and Pb-cultured samples. Concurrently, a strong increase in the occurrence of Heat shock proteins 70 (HSP70) was detected in gametophytes following the pollution gradient. In conclusion, ultrastructural damages can be directly related to HSP 70 occurrence in liverwort tissues, and proportional to the degree of pollution present in the river; thus our study suggests P. neesiana as an affordable bioindicator of freshwaters pollution.

  19. Gypenosides causes DNA damage and inhibits expression of DNA repair genes of human oral cancer SAS cells.

    PubMed

    Lu, Kung-Wen; Chen, Jung-Chou; Lai, Tung-Yuan; Yang, Jai-Sing; Weng, Shu-Wen; Ma, Yi-Shih; Tang, Nou-Ying; Lu, Pei-Jung; Weng, Jing-Ru; Chung, Jing-Gung

    2010-01-01

    Gypenosides (Gyp) are the major components of Gynostemma pentaphyllum Makino, a Chinese medical plant. Recently, Gyp has been shown to induce cell cycle arrest and apoptosis in many human cancer cell lines. However, there is no available information to address the effects of Gyp on DNA damage and DNA repair-associated gene expression in human oral cancer cells. Therefore, we investigated whether Gyp induced DNA damage and DNA repair gene expression in human oral cancer SAS cells. The results from flow cytometric assay indicated that Gyp-induced cytotoxic effects led to a decrease in the percentage of viable SAS cells. The results from comet assay revealed that the incubation of SAS cells with Gyp led to a longer DNA migration smear (comet tail) when compared with control and this effect was dose-dependent. The results from real-time PCR analysis indicated that treatment of SAS cells with 180 mug/ml of Gyp for 24 h led to a decrease in 14-3-3sigma, DNA-dependent serine/threonine protein kinase (DNAPK), p53, ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR) and breast cancer gene 1 (BRCA1) mRNA expression. These observations may explain the cell death caused by Gyp in SAS cells. Taken together, Gyp induced DNA damage and inhibited DNA repair-associated gene expressions in human oral cancer SAS cells in vitro.

  20. A high-fat and cholesterol diet causes fatty liver in guinea pigs. The role of iron and oxidative damage.

    PubMed

    Ye, P; Cheah, I K; Halliwell, B

    2013-08-01

    Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. Iron, cholesterol, and oxidative damage are frequently suggested to be related to the progression of NAFLD, but the precise relationship between them remains unclear. Guinea pigs fed on a high cholesterol and fat diet (without oxidized lipids) generated a disease model of NAFLD with hallmark observations in liver histology and increased liver damage markers. Hepatic cholesterol and iron levels were found to be significantly elevated and directly correlated. Plasma hepcidin and transferrin levels were decreased. Plasma iron concentrations were found to be elevated, likely due to an increased intestinal iron absorption caused by the decrease in plasma hepcidin. However, hepatic transferrin receptor-2 levels were unchanged. No significant increase in hepatic lipid peroxidation was detected using F2-isoprostanes as a reliable biomarker, nor was there a rise in protein carbonyls, a general index of oxidative protein damage. Some increases in cholesterol oxidation products were observed, but largely negated after normalizing for the elevated hepatic cholesterol content. Indeed, increased hemosiderin deposition and unchanged ferritin levels in liver suggested that the excess iron mainly existed as hemosiderin, which is redox-inactive.

  1. Interface Control Document for the EMPACT Module that Estimates Electric Power Transmission System Response to EMP-Caused Damage

    SciTech Connect

    Werley, Kenneth Alan; Mccown, Andrew William

    2016-06-26

    The EPREP code is designed to evaluate the effects of an Electro-Magnetic Pulse (EMP) on the electric power transmission system. The EPREP code embodies an umbrella framework that allows a user to set up analysis conditions and to examine analysis results. The code links to three major physics/engineering modules. The first module describes the EM wave in space and time. The second module evaluates the damage caused by the wave on specific electric power (EP) transmission system components. The third module evaluates the consequence of the damaged network on its (reduced) ability to provide electric power to meet demand. This third module is the focus of the present paper. The EMPACT code serves as the third module. The EMPACT name denotes EMP effects on Alternating Current Transmission systems. The EMPACT algorithms compute electric power transmission network flow solutions under severely damaged network conditions. Initial solutions are often characterized by unacceptible network conditions including line overloads and bad voltages. The EMPACT code contains algorithms to adjust optimally network parameters to eliminate network problems while minimizing outages. System adjustments include automatically adjusting control equipment (generator V control, variable transformers, and variable shunts), as well as non-automatic control of generator power settings and minimal load shedding. The goal is to evaluate the minimal loss of customer load under equilibrium (steady-state) conditions during peak demand.

  2. Homologous Recombination and Translesion DNA Synthesis Play Critical Roles on Tolerating DNA Damage Caused by Trace Levels of Hexavalent Chromium

    PubMed Central

    Chen, Youjun; Zhou, Yi-Hui; Neo, Dayna; Clement, Jean; Takata, Minoru; Takeda, Shunichi; Sale, Julian; Wright, Fred A.; Swenberg, James A.; Nakamura, Jun

    2016-01-01

    Contamination of potentially carcinogenic hexavalent chromium (Cr(VI)) in the drinking water is a major public health concern worldwide. However, little information is available regarding the biological effects of a nanomoler amount of Cr(VI). Here, we investigated the genotoxic effects of Cr(VI) at nanomoler levels and their repair pathways. We found that DNA damage response analyzed based on differential toxicity of isogenic cells deficient in various DNA repair proteins is observed after a three-day incubation with K2CrO4 in REV1-deficient DT40 cells at 19.2 μg/L or higher as well as in TK6 cells deficient in polymerase delta subunit 3 (POLD3) at 9.8 μg/L or higher. The genotoxicity of Cr(VI) decreased ~3000 times when the incubation time was reduced from three days to ten minutes. TK mutation rate also significantly decreased from 6 day to 1 day exposure to Cr(VI). The DNA damage response analysis suggest that DNA repair pathways, including the homologous recombination and REV1- and POLD3-mediated error-prone translesion synthesis pathways, are critical for the cells to tolerate to DNA damage caused by trace amount of Cr(VI). PMID:27907204

  3. Damage caused during hypoxia and reoxygenation in the locomotor muscle of the crab Neohelice granulata (Decapoda: Varunidae).

    PubMed

    Geihs, Márcio Alberto; Vargas, Marcelo Alves; Nery, Luiz Eduardo Maia

    2014-06-01

    The aim of this work was to determine whether different durations of severe hypoxia (0.5 mg O2 L(-1)) followed by reoxygenation cause damage to the locomotor muscle of the crab Neohelice granulata. We evaluated reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential, and aerobic fiber area of the locomotor muscle after different periods of hypoxia (1, 4, or 10h) followed by 30 or 120 min of reoxygenation. Additionally, changes in cell volume, mitochondrial dysfunction, and infiltration of hemocytes were evaluated after hypoxia and a subsequent 2, 24, or 48 h of reoxygenation. After hypoxia, neither ROS nor LPO increased. However, mitochondrial membrane potential and aerobic fiber area decreased in a time-dependent manner. After reoxygenation, the ROS and LPO levels increased and mitochondrial membrane potential decreased, but these quickly recovered in crabs exposed to 4h of hypoxia. On the other hand, alterations of mitochondria resulted in morphological changes in aerobic fibers, which required more time to recover during reoxygenation after 10h of hypoxia. The locomotor muscles of the crab N. granulata suffer damage after hypoxia and reoxygenation. The intensity of this damage is dependent on the duration of hypoxia. In all experimental situations analyzed, the locomotor muscle of this crab was capable of recovery.

  4. Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake.

    PubMed

    Nobre, Manoel Jorge

    2016-12-01

    Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake.

  5. Aluminium-induced excessive ROS causes cellular damage and metabolic shifts in black gram Vigna mungo (L.) Hepper.

    PubMed

    Chowra, Umakanta; Yanase, Emiko; Koyama, Hiroyuki; Panda, Sanjib Kumar

    2017-01-01

    Aluminium-induced oxidative damage caused by excessive ROS production was evaluated in black gram pulse crop. Black gram plants were treated with different aluminium (Al(3+)) concentrations (10, 50 and 100 μM with pH 4.7) and further the effects of Al(3+) were characterised by means of root growth inhibition, histochemical assay, ROS content analysis, protein carbonylation quantification and (1)H-NMR analysis. The results showed that aluminium induces excessive ROS production which leads to cellular damage, root injury, stunt root growth and other metabolic shifts. In black gram, Al(3+) induces cellular damage at the earliest stage of stress which was characterised from histochemical analysis. From this study, it was observed that prolonged stress can activate certain aluminium detoxification defence mechanism. Probably excessive ROS triggers such defence mechanism in black gram. Al(3+) can induce excessive ROS initially in the root region then transported to other parts of the plant. As much as the Al(3+) concentration increases, the rate of cellular injury and ROS production also increases. But after 72 h of stress, plants showed a lowered ROS level and cellular damage which indicates the upregulation of defensive mechanisms. Metabolic shift analysis also showed that the black gram plant under stress has less metabolic content after 24 h of treatment, but gradually, it was increased after 72 h of treatment. It was assumed that ROS played the most important role as a signalling molecule for aluminium stress in black gram.

  6. Deficiency of the multi-copy mouse Y gene Sly causes sperm DNA damage and abnormal chromatin packaging.

    PubMed

    Riel, Jonathan M; Yamauchi, Yasuhiro; Sugawara, Atsushi; Li, Ho Yan J; Ruthig, Victor; Stoytcheva, Zoia; Ellis, Peter J I; Cocquet, Julie; Ward, Monika A

    2013-02-01

    In mouse and man Y chromosome deletions are frequently associated with spermatogenic defects. Mice with extensive deletions of non-pairing Y chromosome long arm (NPYq) are infertile and produce sperm with grossly misshapen heads, abnormal chromatin packaging and DNA damage. The NPYq-encoded multi-copy gene Sly controls the expression of sex chromosome genes after meiosis and Sly deficiency results in a remarkable upregulation of sex chromosome genes. Sly deficiency has been shown to be the underlying cause of the sperm head anomalies and infertility associated with NPYq gene loss, but it was not known whether it recapitulates sperm DNA damage phenotype. We produced and examined mice with transgenically (RNAi) silenced Sly and demonstrated that these mice have increased incidence of sperm with DNA damage and poorly condensed and insufficiently protaminated chromatin. We also investigated the contribution of each of the two Sly-encoded transcript variants and noted that the phenotype was only observed when both variants were knocked down, and that the phenotype was intermediate in severity compared with mice with severe NPYq deficiency. Our data demonstrate that Sly deficiency is responsible for the sperm DNA damage/chromatin packaging defects observed in mice with NPYq deletions and point to SLY proteins involvement in chromatin reprogramming during spermiogenesis, probably through their effect on the post-meiotic expression of spermiogenic genes. Considering the importance of the sperm epigenome for embryonic and fetal development and the possibility of its inter-generational transmission, our results are important for future investigations of the molecular mechanisms of this biologically and clinically important process.

  7. Iatrogenic Damage to the Periodontium Caused by Fixed Prosthodontic Treatment Procedures

    PubMed Central

    Harish, PV; Joseph, Sonila Anne; Sirajuddin, Syed; Gundapaneni, Veenadharini; Chungkham, Sachidananda; ., Ambica

    2015-01-01

    Missing teeth should be replaced as soon as possible to maintain arch integrity and thereby avoid both morphologic and functional derangements in the occlusion. Otherwise, changes occur that upset the masticatory system, such as extrusion of the teeth opposing the edentulous areas along with their alveolar housing, their supporting tissues and ultimately the maxillary sinus. Concurrently with extrusion, shifting of the interproximal contacts and migration of the adjacent teeth occur, thereby impairing function and causing disharmony. Good oral health cannot be achieved when changes in tooth position alter the coronal contour and occlusion interfering with mutual support, which encourages food impaction and retention, further leading to osseous defects.

  8. Transgenic expression of the deoxynucleotide carrier causes mitochondrial damage that is enhanced by NRTIs for AIDS.

    PubMed

    Lewis, William; Haase, Chad P; Miller, Yoon K; Ferguson, Brandy; Stuart, Tami; Ludaway, Tomika; McNaught, Jamie; Russ, Rodney; Steltzer, Jeffrey; Santoianni, Robert; Long, Robert; Fiermonte, Giuseppe; Palmieri, Ferdinando

    2005-08-01

    Nucleoside reverse transcriptase inhibitors (NRTIs) are antiretrovirals for AIDS with limiting mitochondrial side effects. The mitochondrial deoxynucleotide carrier (DNC) transports phosphorylated nucleosides for mitochondrial DNA replication and can transport phosphorylated NRTIs into mitochondria. Transgenic mice (TG) that exclusively overexpress DNC in the heart tested DNC's role in mitochondrial dysfunction from NRTIs. Two TG lines were created that overexpressed the human DNC gene in murine myocardium. Cardiac and mitochondrial structure and function were examined by magnetic resonance imaging, echocardiography, electrocardiography, transmission electron microscopy, and plasma lactate. Antiretroviral combinations (HAART) that contained NRTIs (stavudine (2', 3'-didehydro-2', 3'-deoxythymidine or d4T)/lamivudine/indinavir; or zidovudine (3' azido-3'-deoxythymidine or AZT)/lamivudine/indinavir; 35 days) were administered to simulate AIDS therapy. In parallel, a HAART combination without NRTIs (nevirapine/efavirenz/indinavir; 35 days) served as an NRTI-sparing, control regimen. Untreated DNC TGs exhibited normal cardiac function but abnormal mitochondrial ultrastructure. HAART that contained NRTIs caused cardiomyopathy in TGs with increased left ventricle mass and volume, heart rate variability, and worse mitochondrial ultrastructural defects. In contrast, treatment with an NRTI-sparing HAART regimen caused no cardiac changes. Data suggest the DNC is integral to mitochondrial homeostasis in vivo and may relate mechanistically to mitochondrial dysfunction in patients treated with HAART regimens that contain NRTIs.

  9. Low-temperature atmospheric plasma increases the expression of anti-aging genes of skin cells without causing cellular damages.

    PubMed

    Choi, Jeong-Hae; Lee, Hyun-Wook; Lee, Jae-Koo; Hong, Jin-woo; Kim, Gyoo-cheon

    2013-03-01

    Efforts to employ various types of plasma in the field of skin care have increased consistently because it can regulate many biochemical reactions that are normally unaffected by light-based therapy. One method for skin rejuvenation adopted a high-temperature plasma generator to remove skin epithelial cells. In this case, the catalyzing effects of the plasma were rarely used due to the high temperature. Hence, the benefits of the plasma were not magnified. Recently, many types of low-temperature plasma devices have been developed for medical applications but their detailed functions and working mechanisms are unclear. The present study examined the effect of low-temperature microwave plasma on skin cells. Treatment with low-temperature plasma increased the expression of anti-aging genes in skin cells, including collagen, fibronectin and vascular endothelial growth factor. Furthermore, the plasma treatment did not cause cell death, but only induced slight cell growth arrest at the G2 phase. Although the cells treated with low-temperature plasma showed moderate growth arrest, there were no signs of thermal or genetic damage of skin cells. Overall, this low-temperature microwave plasma device induces the expressions of some anti-aging-related genes in skin cells without causing damage.

  10. Reoxygenation-induced mitochondrial damage is caused by the Ca2+-dependent mitochondrial inner membrane permeability transition.

    PubMed

    Tanaka, T; Hakoda, S; Takeyama, N

    1998-07-01

    Anoxia/reoxygenation injury of isolated rat liver mitochondria was investigated. During anoxia of up to 60 min, the membrane potential was largely preserved and mitochondrial swelling was not observed. Reoxygenation of anoxic mitochondria rapidly caused swelling, cyclosporin A-sensitive Ca2+ efflux, [14C]sucrose trapping, and loss of the membrane potential along with increased generation of reactive oxygen intermediates (ROI). Although pretreatment with catalase and superoxide dismutase completely abolished reoxygenation-induced generation of ROI, mitochondrial damage was not prevented, as indicated by swelling, loss of the membrane potential, a decrease of the ATP content, and cyclosporin A-sensitive Ca2+ efflux. However, addition of the immunosuppressant cyclosporin A or addition of ADP completely prevented the mitochondrial damage induced by reoxygenation. The same protective effect was noted when Ca2+ cycling was prevented, either by chelating Ca2+ with EGTA or by inhibiting Ca2+ reuptake with ruthenium red. These findings indicate that mitochondrial anoxia/reoxygenation injury is caused by the cyclosporin A-sensitive and Ca2+-dependent membrane permeability transition. In contrast, reoxygenation injury does not appear to be triggered by the enhanced production of ROI.

  11. GPR measurements and estimation for road subgrade damage caused by neighboring train vibration load

    NASA Astrophysics Data System (ADS)

    Zhao, Yonghui; Lu, Gang; Ge, Shuangcheng

    2015-04-01

    Generally, road can be simplified as a three-layer structure, including subgrade, subbase and pavement. Subgrade is the native material underneath a constructed road. It is commonly compacted before the road construction, and sometimes stabilized by the addition of asphalt, lime or other modifiers. As the mainly supporting structure, subgrade damage would lead in pavement settlement, displacement and crack. Assessment and monitoring of the subgrade condition currently involves trial pitting and subgrade sampling. However there is a practical limit on spatial density at which trail pits and cores can be taken. Ground penetrating radar (GPR) has been widely used to characterize highway pavement profiling, concrete structure inspection and railroad track ballast estimation. GPR can improve the economics of road maintenance. Long-term train vibration load might seriously influence the stability of the subgrade of neighboring road. Pavement settlement and obvious cracks have been found at a municipal road cross-under a railway with culvert box method. GPR test was conducted to estimate the subgrade and soil within 2.0 m depth for the further road maintenance. Two survey lines were designed in each lane, and total 12 GPR sections have been implemented. Considering both the penetrating range and the resolution, a antenna with a 500 MHz central frequency was chosen for on-site GPR data collection. For data acquisition, we used the default operating environment and scanning parameters for the RAMAC system: 60kHz transmission rate, 50 ns time window, 1024 samples per scan and 0.1 m step-size. Continuous operation was used; the antenna was placed on the road surface and slowly moved along the road. The strong surrounding disturbance related to railroad and attachments, might decrease the reliability of interpretation results. Some routine process methods (including the background removing, filtering) have been applied to suppress the background noise. Additionally, attribute

  12. Chronic exposure to nanoparticulate TiO2 causes renal fibrosis involving activation of the Wnt pathway in mouse kidney.

    PubMed

    Hong, Fashui; Hong, Jie; Wang, Ling; Zhou, Yingjun; Liu, Dong; Xu, Bingqing; Yu, Xiaohong; Sheng, Lei

    2015-02-11

    Chronic exposure to nano-TiO2 may induce renal fibrosis, and the mechanism of this process is not well understood. Therefore, in this study, mice were administered nano-TiO2 by intragastric feeding for 9 months, and the urinary levels of nephrotoxicity biomarkers, activation of the Wnt pathway, and markers of the epithelial-to-mesenchymal transition (EMT) in the kidneys were investigated. The findings suggested that exposure to nano-TiO2 increased the level of renal titanium accumulation, urinary levels of kidney injury molecule-1 (1.18 ± 0.13- to 3.60 ± 0.41-fold), clusterin (1.40 ± 0.16- to 5.14 ± 0.58-fold), and osteopontin (0.71 ± 0.08- to 2.41 ± 0.29-fold), and increased levels of renal inflammation and fibrosis. Furthermore, nano-TiO2 increased the level of expression of Wnt ligands (Wnt1, Wnt2, Wnt3, Wnt4, Wnt5a, Wnt6, Wnt7a, Wnt9a, Wnt10a, and Wnt11, 0.09 ± 0.02- to 4.84 ± 0.52-fold), Wnt receptors Frizzled (Fz1, Fz5, and Fz7, 0.37 ± 0.04- to 8.57 ± 0.91-fold), and coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (0.73 ± 0.09- to 5.27 ± 0.56-fold) in the kidney. Wnt signaling components induced by nano-TiO2 were corroborated by decreased levels of expression of Wnt antagonist-related markers (Dkk1, Dkk2, Dkk3, Dkk4, and sFRP/FrzB, -0.06 ± 0.01- to -0.87 ± 0.09-fold) and increased levels of expression of Wnt target genes (Abcb1b, cyclin D1, and Myc, 0.03 ± 0.01- to 2.73 ± 0.28-fold) and EMT markers Colla1, Fn, Twist, and α-SMA (0.06 ± 0.02- to 5.80 ± 0.61-fold). These findings indicate that nano-TiO2 induced renal fibrosis that may be mediated via Wnt signaling.

  13. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    PubMed Central

    Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft. PMID:27725836

  14. Recurrence of Acute Page Kidney in a Renal Transplant Allograft.

    PubMed

    Kapoor, Rajan; Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.

  15. Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.

    PubMed

    Miner, Jonathan J; Cao, Bin; Govero, Jennifer; Smith, Amber M; Fernandez, Estefania; Cabrera, Omar H; Garber, Charise; Noll, Michelle; Klein, Robyn S; Noguchi, Kevin K; Mysorekar, Indira U; Diamond, Michael S

    2016-05-19

    Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations.

  16. Valuing the human health damage caused by the fraud of Volkswagen.

    PubMed

    Oldenkamp, Rik; van Zelm, Rosalie; Huijbregts, Mark A J

    2016-05-01

    Recently it became known that Volkswagen Group has been cheating with emission tests for diesel engines over the last six years, resulting in on-road emissions vastly exceeding legal standards for nitrogen oxides in Europe and the United States. Here, we provide an estimate of the public health consequences caused by this fraud. From 2009 to 2015, approximately nine million fraudulent Volkswagen cars, as sold in Europe and the US, emitted a cumulative amount of 526 ktonnes of nitrogen oxides more than was legally allowed. These fraudulent emissions are associated with 45 thousand disability-adjusted life years (DALYs) and a value of life lost of at least 39 billion US dollars, which is approximately 5.3 times larger than the 7.3 billion US dollars that Volkswagen Group has set aside to cover worldwide costs related to the diesel emissions scandal.

  17. Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome

    PubMed Central

    Ward, Christopher S.; Huang, Teng-Wei; Herrera, José A.; Samaco, Rodney C.; Pitcher, Meagan R.; Herron, Alan; Skinner, Steven A.; Kaufmann, Walter E.; Glaze, Daniel G.; Percy, Alan K.; Neul, Jeffrey L.

    2016-01-01

    Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized. PMID:27828991

  18. Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome.

    PubMed

    Ward, Christopher S; Huang, Teng-Wei; Herrera, José A; Samaco, Rodney C; Pitcher, Meagan R; Herron, Alan; Skinner, Steven A; Kaufmann, Walter E; Glaze, Daniel G; Percy, Alan K; Neul, Jeffrey L

    2016-01-01

    Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized.

  19. Chlorinated river and lake water extract caused oxidative damage, DNA migration and cytotoxicity in human cells.

    PubMed

    Yuan, Jing; Wu, Xin-Jiang; Lu, Wen-Qing; Cheng, Xiao-Li; Chen, Dan; Li, Xiao-Yan; Liu, Ai-Lin; Wu, Jian-Jun; Xie, Hong; Stahl, Thorsten; Mersch-Sundermann, Volker

    2005-01-01

    Consumption of chlorinated drinking water is suspected to be associated with adverse health effects, including mutations and cancer. In the present study, the genotoxic potential of water from Donghu lake, Yangtze river and Hanjiang river in Wuhan, an 8-million metropolis in China, was investigated using HepG2 cells and the alkaline version of the comet assay. It could be shown that all water extracts caused dose-dependent DNA migration in concentrations corresponding to dried extracts of 0.167-167 ml chlorinated drinking water per ml medium. To explore whether the intracellular redox status is regulated by chlorinated drinking water, we determined lipid peroxidation (LPO) and depletion of reduced glutathione (GSH). The malondialdehyde (thiobarbituric acid (TBA)-reactive aldehydes) concentration increased after chlorinated drinking water treatment of HepG2 cells in a dose-dependent manner, the GSH content decreased. The activity of lactate dehydrogenase (LDH) increased in chlorinated drinking water treated HepG2 cells indicating cytotoxicity. In accordance with former studies which dealt with in vivo and in vitro micronucleus induction the present study shows that chlorinated drinking water from polluted raw water may entail genetic risks.

  20. Peptoids successfully inhibit the growth of gram negative E. coli causing substantial membrane damage

    PubMed Central

    Mojsoska, Biljana; Carretero, Gustavo; Larsen, Sylvester; Mateiu, Ramona Valentina; Jenssen, Håvard

    2017-01-01

    Peptoids are an alternative approach to antimicrobial peptides that offer higher stability towards enzymatic degradation. It is essential when developing new types of peptoids, that mimic the function of antimicrobial peptides, to understand their mechanism of action. Few studies on the specific mechanism of action of antimicrobial peptoids have been described in the literature, despite the plethora of studies on the mode of action of antimicrobial peptides. Here, we investigate the mechanism of action of two short cationic peptoids, rich in lysine and tryptophan side chain functionalities. We demonstrate that both peptoids are able to cause loss of viability in E. coli susceptible cells at their MIC (16–32 μg/ml) concentrations. Dye leakage assays demonstrate slow and low membrane permeabilization for peptoid 1, that is still higher for lipid compositions mimicking bacterial membranes than lipid compositions containing Cholesterol. At concentrations of 4 × MIC (64–128 μg/ml), pore formation, leakage of cytoplasmic content and filamentation were the most commonly observed morphological changes seen by SEM in E. coli treated with both peptoids. Flow cytometry data supports the increase of cell size as observed in the quantification analysis from the SEM images and suggests overall decrease of DNA per cell mass over time. PMID:28195195

  1. Simulated climate change causes immune suppression and protein damage in the crustacean Nephrops norvegicus.

    PubMed

    Hernroth, Bodil; Sköld, Helen Nilsson; Wiklander, Kerstin; Jutfelt, Fredrik; Baden, Susanne

    2012-11-01

    Rising atmospheric carbon dioxide concentration is causing global warming, which affects oceans by elevating water temperature and reducing pH. Crustaceans have been considered tolerant to ocean acidification because of their retained capacity to calcify during subnormal pH. However, we report here that significant immune suppression of the Norway lobster, Nephrops norvegicus, occurs after a 4-month exposure to ocean acidification (OA) at a level predicted for the year 2100 (hypercapnic seawater with a pH lowered by 0.4 units). Experiments carried out at different temperatures (5, 10, 12, 14, 16, and 18°C) demonstrated that the temperature within this range alone did not affect lobster immune responses. In the OA-treatment, hemocyte numbers were reduced by almost 50% and the phagocytic capacity of the remaining hemocytes was inhibited by 60%. The reduction in hemocyte numbers was not due to increased apoptosis in hematopoetic tissue. Cellular responses to stress were investigated through evaluating advanced glycation end products (AGE) and lipid oxidation in lobster hepatopancreata, and OA-treatment was shown to significantly increase AGEs', indicating stress-induced protein alterations. Furthermore, the extracellular pH of lobster hemolymph was reduced by approximately 0.2 units in the OA-treatment group, indicating either limited pH compensation or buffering capacity. The negative effects of OA-treatment on the nephropidae immune response and tissue homeostasis were more pronounced at higher temperatures (12-18°C versus 5°C), which may potentially affect disease severity and spread. Our results signify that ocean acidification may have adverse effects on the physiology of lobsters, which previously had been overlooked in studies of basic parameters such as lobster growth or calcification.

  2. Dominant repression by Arabidopsis transcription factor MYB44 causes oxidative damage and hypersensitivity to abiotic stress.

    PubMed

    Persak, Helene; Pitzschke, Andrea

    2014-02-13

    In any living species, stress adaptation is closely linked with major changes of the gene expression profile. As a substrate protein of the rapidly stress-induced mitogen-activated protein kinase MPK3, Arabidopsis transcription factor MYB44 likely acts at the front line of stress-induced re-programming. We recently characterized MYB44 as phosphorylation-dependent positive regulator of salt stress signaling. Molecular events downstream of MYB44 are largely unknown. Although MYB44 binds to the MBSII element in vitro, it has no discernible effect on MBSII-driven reporter gene expression in plant co-transfection assays. This may suggest limited abundance of a synergistic co-regulator. MYB44 carries a putative transcriptional repression (Ethylene responsive element binding factor-associated Amphiphilic Repression, EAR) motif. We employed a dominant repressor strategy to gain insights into MYB44-conferred stress resistance. Overexpression of a MYB44-REP fusion markedly compromised salt and drought stress tolerance--the opposite was seen in MYB44 overexpression lines. MYB44-mediated resistance likely results from induction of tolerance-enhancing, rather than from repression of tolerance-diminishing factors. Salt stress-induced accumulation of destructive reactive oxygen species is efficiently prevented in transgenic MYB44, but accelerated in MYB44-REP lines. Furthermore, heterologous overexpression of MYB44-REP caused tissue collapse in Nicotiana. A mechanistic model of MAPK-MYB-mediated enhancement in the antioxidative capacity and stress tolerance is proposed. Genetic engineering of MYB44 variants with higher trans-activating capacity may be a means to further raise stress resistance in crops.

  3. Can Diopatra neapolitana (Annelida: Onuphidae) regenerate body damage caused by bait digging or predation?

    NASA Astrophysics Data System (ADS)

    Pires, A.; Freitas, R.; Quintino, V.; Rodrigues, A. M.

    2012-09-01

    The regenerative ability of Diopatra neapolitana was evaluated under laboratory conditions following nine experimental amputation levels: before the beginning of the branchiae (chaetiger 3 or 4), in the branchial region, at chaetigers 10, 15, 20, 25, 30, 35 and 40 and after the branchiae, at chaetigers 45-55. Specimens amputated at the 20th chaetiger were not able to regenerate and did not survive. The posterior portion of the specimens amputated up to chaetiger 15, regenerated the anterior part but the anterior ends were unable to survive. The anterior end of the specimens amputated at and beyond the 25th chaetiger regenerated the posterior part but the posterior ends were not able to regenerate an anterior part. Percent survival was directly related to the number of branchial segments left in the regenerating specimen and reached 100% only when the specimens were amputated beyond the branchial region. These results indicate that the species has regenerative ability and should survive the loss of a few anterior chaetigers, namely caused by predation. However, the results also indicate that bait digging could impair the survival of the posterior part remaining in the tube, as usually more than 20 chaetigers are harvested by bait collectors. Regarding field-collected specimens, D. neapolitana was found regenerating a mean of 9.0 ± 2.51 chaetigers, and Diopatra marocensis 7.5 ± 1.93 chaetigers, at the anterior end. The higher percentage of field-collected specimens showing regeneration of the anterior end belonged to D. marocensis. Only very few specimens, for both species, were found regenerating the posterior part of the body.

  4. Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease

    PubMed Central

    Nascimento, M.M.; Hayashi, S.Y.; Riella, M.C.; Lindholm, B.

    2014-01-01

    Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and plays a role in vascular calcification. We evaluated the relationship between osteoprotegerin levels and inflammatory markers, atherosclerosis, and mortality in patients with stages 3-5 chronic kidney disease. A total of 145 subjects (median age 61 years, 61% men; 36 patients on hemodialysis, 55 patients on peritoneal dialysis, and 54 patients with stages 3-5 chronic kidney disease) were studied. Clinical characteristics, markers of mineral metabolism (including fibroblast growth factor-23 [FGF-23]) and inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6 [IL-6]), and the intima-media thickness (IMT) in the common carotid arteries were measured at baseline. Cardiac function was assessed by color tissue Doppler echocardiography. After 36 months follow-up, the survival rate by Kaplan-Meier analysis was significantly different according to OPG levels (χ 2=14.33; P=0.002). Increased OPG levels were positively associated with IL-6 (r=0.38, P<0.001), FGF-23 (r=0.26, P<0.001) and hsCRP (r=0.0.24, P=0.003). In addition, OPG was positively associated with troponin I (r=0.54, P<0.001) and IMT (r=0.39, P<0.0001). Finally, in Cox analysis, only OPG (HR=1.07, 95%CI=1.02-1.13) and hsCRP (HR=1.02, 95%CI=1.01-1.04) were independently associated with increased risk of death. These results suggested that elevated levels of serum OPG might be associated with atherosclerosis and all-cause mortality in patients with chronic kidney disease. PMID:25296363

  5. 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

  6. Avocado oil induces long-term alleviation of oxidative damage in kidney mitochondria from type 2 diabetic rats by improving glutathione status.

    PubMed

    Ortiz-Avila, Omar; Figueroa-García, María Del Consuelo; García-Berumen, Claudia Isabel; Calderón-Cortés, Elizabeth; Mejía-Barajas, Jorge A; Rodriguez-Orozco, Alain R; Mejía-Zepeda, Ricardo; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

    2017-04-01

    Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion. Therefore, we tested during 1 year the effects of avocado oil on glycemia, ROS levels, lipid peroxidation and glutathione status in kidney mitochondria from type 2 diabetic Goto-Kakizaki rats. Diabetic rats exhibited glycemia of 120-186 mg/dL the first 9 months with a further increase to 250-300 mg/dL. Avocado oil decreased hyperglycemia at intermediate levels between diabetic and control rats. Diabetic rats displayed augmented lipid peroxidation and depletion of reduced glutathione throughout the study, while increased ROS generation was observed at the 3rd and 12th months along with diminished content of total glutathione at the 6th and 12th months. Avocado oil ameliorated all these defects and augmented the mitochondrial content of oleic acid. The beneficial effects of avocado oil are discussed in terms of the hypoglycemic effect of oleic acid and the probable dependence of glutathione transport on lipid peroxidation and thiol oxidation of mitochondrial carriers.

  7. Medical costs incurred by organ damage caused by active disease, comorbidities and side effect of treatments in systemic lupus erythematosus patients: a Taiwan nationwide population-based study.

    PubMed

    Chiu, Y M; Chuang, M T; Lang, H C

    2016-11-01

    This study aims to systematically investigate the medial expenditures incurred by systemic lupus erythematosus (SLE)-associated organ damages in order to assess the economic impact of damage accrual by active disease, comorbidities and side effect of treatments. In total, 22,258 SLE cases were identified from the National Health Insurance Research Database, and organ damages assessed were according to the list from Systemic Lupus International Collaborative Clinic/American Rheumatology damage index system. Medical expenditures incurred by organ damages in the first as well as the subsequent year were obtained from the database. Our data reflected that organ damages caused by active disease and comorbidities, such those of renal, neuropsychiatric, pulmonary and cardiovascular systems are among the highest costing of all damage items. This study also shows that significant medical expenditures are incurred by damage items such as those occurring in ocular and musculoskeletal systems, which are typically caused by side effect of treatments such as corticosteroids. The medical expenditure in subsequent year still causes substantial economic burden. This systematic and continuous survey provided important reference of disease burden of SLE.

  8. High-Throughput Sequencing Reveals Circulating miRNAs as Potential Biomarkers of Kidney Damage in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Pacheco-Lugo, Lisandro; Lorenzi, Hernan; Díaz-Olmos, Yirys; Almendrales, Lisneth; Rico, Edwin; Navarro, Roberto; España-Puccini, Pierine; Iglesias, Antonio; Egea, Eduardo; Aroca, Gustavo

    2016-01-01

    Renal involvement is one of the most severe manifestations of systemic lupus erythematosus (SLE). Renal biopsy is the gold standard when it comes to knowing whether a patient has lupus nephritis, and the degree of renal disease present. However, the biopsy has various complications, bleeding being the most common. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with SLE is a priority. Micro RNAs (miRNAs) are differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. The aim of this study was to identify changes in the abundance of miRNAs in plasma samples from patients with lupus nephritis that could potentially allow the diagnosis of renal damage in SLE patients. This is an observational case-control cross-sectional study, in which we characterized the differential abundance profiles of miRNAs among patients with different degrees of lupus compared with SLE patients without renal involvement and healthy control individuals. We found 89 miRNAs with changes in their abundance between lupus nephritis patients and healthy controls, and 17 miRNAs that showed significant variations between SLE patients with or without renal involvement. Validation for qPCR of a group of miRNAs on additional samples from lupus patients with or without nephritis, and from healthy individuals, showed that five miRNAs presented an average detection sensitivity of 97%, a specificity of 70.3%, a positive predictive value of 82.5%, a negative predictive value of 96% and a diagnosis efficiency of 87.9%. These results strongly suggest that miR-221-5p, miR-380-3p, miR-556-5p, miR-758-3p and miR-3074-3p are potential diagnostic biomarkers of lupus nephritis in patients with SLE. The observed differential pattern of miRNA abundance may have functional implications in the pathophysiology of SLE renal damage. PMID:27835701

  9. High-Throughput Sequencing Reveals Circulating miRNAs as Potential Biomarkers of Kidney Damage in Patients with Systemic Lupus Erythematosus.

    PubMed

    Navarro-Quiroz, Elkin; Pacheco-Lugo, Lisandro; Lorenzi, Hernan; Díaz-Olmos, Yirys; Almendrales, Lisneth; Rico, Edwin; Navarro, Roberto; España-Puccini, Pierine; Iglesias, Antonio; Egea, Eduardo; Aroca, Gustavo

    2016-01-01

    Renal involvement is one of the most severe manifestations of systemic lupus erythematosus (SLE). Renal biopsy is the gold standard when it comes to knowing whether a patient has lupus nephritis, and the degree of renal disease present. However, the biopsy has various complications, bleeding being the most common. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with SLE is a priority. Micro RNAs (miRNAs) are differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. The aim of this study was to identify changes in the abundance of miRNAs in plasma samples from patients with lupus nephritis that could potentially allow the diagnosis of renal damage in SLE patients. This is an observational case-control cross-sectional study, in which we characterized the differential abundance profiles of miRNAs among patients with different degrees of lupus compared with SLE patients without renal involvement and healthy control individuals. We found 89 miRNAs with changes in their abundance between lupus nephritis patients and healthy controls, and 17 miRNAs that showed significant variations between SLE patients with or without renal involvement. Validation for qPCR of a group of miRNAs on additional samples from lupus patients with or without nephritis, and from healthy individuals, showed that five miRNAs presented an average detection sensitivity of 97%, a specificity of 70.3%, a positive predictive value of 82.5%, a negative predictive value of 96% and a diagnosis efficiency of 87.9%. These results strongly suggest that miR-221-5p, miR-380-3p, miR-556-5p, miR-758-3p and miR-3074-3p are potential diagnostic biomarkers of lupus nephritis in patients with SLE. The observed differential pattern of miRNA abundance may have functional implications in the pathophysiology of SLE renal damage.

  10. Oxidative damage of U937 human leukemic cells caused by hydroxyl radical results in singlet oxygen formation.

    PubMed

    Rác, Marek; Křupka, Michal; Binder, Svatopluk; Sedlářová, Michaela; Matušková, Zuzana; Raška, Milan; Pospíšil, Pavel

    2015-01-01

    The exposure of human cells to oxidative stress leads to the oxidation of biomolecules such as lipids, proteins and nuclei acids. In this study, the oxidation of lipids, proteins and DNA was studied after the addition of hydrogen peroxide and Fenton reagent to cell suspension containing human leukemic monocyte lymphoma cell line U937. EPR spin-trapping data showed that the addition of hydrogen peroxide to the cell suspension formed hydroxyl radical via Fenton reaction mediated by endogenous metals. The malondialdehyde HPLC analysis showed no lipid peroxidation after the addition of hydrogen peroxide, whereas the Fenton reagent caused significant lipid peroxidation. The formation of protein carbonyls monitored by dot blot immunoassay and the DNA fragmentation measured by comet assay occurred after the addition of both hydrogen peroxide and Fenton reagent. Oxidative damage of biomolecules leads to the formation of singlet oxygen as conformed by EPR spin-trapping spectroscopy and the green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. It is proposed here that singlet oxygen is formed by the decomposition of high-energy intermediates such as dioxetane or tetroxide formed by oxidative damage of biomolecules.

  11. Evaluation of melioration area damage on the river Danube caused by the hydroelectric power plant 'Djerdap 1' backwater.

    PubMed

    Pajic, P; Andjelic, L; Urosevic, U; Polomcic, D

    2014-01-01

    Construction of the hydroelectric power plant (HPP) 'Djerdap 1' formed a backwater effect on the Danube and its tributaries, which had an inevitable influence on groundwater level, causing it to rise and thus creating additional threats to all melioration areas on more than 300 km of the Danube riversides, as well as on the riversides of its tributaries: the Sava (100 km) and the Tisa (60 km). In this paper, the HPP 'Djerdap 1' backwater effect on some characteristic melioration areas (34 in all) has been analyzed. In most of these areas intensive agricultural activity has always been present. An assessment of agricultural production damage was carried out by complex hydrodynamic calculations (60 calculation profiles) for different backwater regimes, with the aim to precisely quantify the HPP 'Djerdap 1' backwater effect on groundwater piezometric levels. Combining them with complex agroeconomic analyses, the aim is to quantify agricultural production damage and to consider the perspective of melioration area users. This method, which combines two different, but compatible, aspects of the melioration area threat assessment (hydrodynamic and agroeconomic), may present a quality base for further agricultural production threat assessment on all melioration areas on the Danube riversides, with the final aim to consider the economic effects and the importance of its further protection.

  12. Intense THz pulses cause H2AX phosphorylation and activate DNA damage response in human skin tissue

    PubMed Central

    Titova, Lyubov V.; Ayesheshim, Ayesheshim K.; Golubov, Andrey; Fogen, Dawson; Rodriguez-Juarez, Rocio; Hegmann, Frank A.; Kovalchuk, Olga

    2013-01-01

    Recent emergence and growing use of terahertz (THz) radiation for medical imaging and public security screening raise questions on reasonable levels of exposure and health consequences of this form of electromagnetic radiation. In particular, picosecond-duration THz pulses have shown promise for novel diagnostic imaging techniques. However, the effects of THz pulses on human cells and tissues thus far remain largely unknown. We report on the investigation of the biological effects of pulsed THz radiation on artificial human skin tissues. We observe that exposure to intense THz pulses for ten minutes leads to a significant induction of H2AX phosphorylation, indicating that THz pulse irradiation may cause DNA damage in exposed skin tissue. At the same time, we find a THz-pulse-induced increase in the levels of several proteins responsible for cell-cycle regulation and tumor suppression, suggesting that DNA damage repair mechanisms are quickly activated. Furthermore, we find that the cellular response to pulsed THz radiation is significantly different from that induced by exposure to UVA (400 nm). PMID:23577291

  13. Oxidative Damage of U937 Human Leukemic Cells Caused by Hydroxyl Radical Results in Singlet Oxygen Formation

    PubMed Central

    Rác, Marek; Křupka, Michal; Binder, Svatopluk; Sedlářová, Michaela; Matušková, Zuzana; Raška, Milan; Pospíšil, Pavel

    2015-01-01

    The exposure of human cells to oxidative stress leads to the oxidation of biomolecules such as lipids, proteins and nuclei acids. In this study, the oxidation of lipids, proteins and DNA was studied after the addition of hydrogen peroxide and Fenton reagent to cell suspension containing human leukemic monocyte lymphoma cell line U937. EPR spin-trapping data showed that the addition of hydrogen peroxide to the cell suspension formed hydroxyl radical via Fenton reaction mediated by endogenous metals. The malondialdehyde HPLC analysis showed no lipid peroxidation after the addition of hydrogen peroxide, whereas the Fenton reagent caused significant lipid peroxidation. The formation of protein carbonyls monitored by dot blot immunoassay and the DNA fragmentation measured by comet assay occurred after the addition of both hydrogen peroxide and Fenton reagent. Oxidative damage of biomolecules leads to the formation of singlet oxygen as conformed by EPR spin-trapping spectroscopy and the green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. It is proposed here that singlet oxygen is formed by the decomposition of high-energy intermediates such as dioxetane or tetroxide formed by oxidative damage of biomolecules. PMID:25730422

  14. Chronic Kidney Disease in Kidney Stone Formers

    PubMed Central

    Krambeck, Amy E.; Lieske, John C.

    2011-01-01

    Summary Recent population studies have found symptomatic kidney stone formers to be at increased risk for chronic kidney disease (CKD). Although kidney stones are not commonly identified as the primary cause of ESRD, they still may be important contributing factors. Paradoxically, CKD can be protective against forming kidney stones because of the substantial reduction in urine calcium excretion. Among stone formers, those with rare hereditary diseases (cystinuria, primary hyperoxaluria, Dent disease, and 2,8 dihydroxyadenine stones), recurrent urinary tract infections, struvite stones, hypertension, and diabetes seem to be at highest risk for CKD. The primary mechanism for CKD from kidney stones is usually attributed to an obstructive uropathy or pyelonephritis, but crystal plugs at the ducts of Bellini and parenchymal injury from shockwave lithotripsy may also contribute. The historical shift to less invasive surgical management of kidney stones has likely had a beneficial impact on the risk for CKD. Among potential kidney donors, past symptomatic kidney stones but not radiographic stones found on computed tomography scans were associated with albuminuria. Kidney stones detected by ultrasound screening have also been associated with CKD in the general population. Further studies that better classify CKD, better characterize stone formers, more thoroughly address potential confounding by comorbidities, and have active instead of passive follow-up to avoid detection bias are needed. PMID:21784825

  15. Medical plant extracts and natural compounds with a hepatoprotective effect against damage caused by antitubercular drugs: A review.

    PubMed

    Jiménez-Arellanes, María Adelina; Gutiérrez-Rebolledo, Gabriel Alfonso; Meckes-Fischer, Mariana; León-Díaz, Rosalba

    2016-12-01

    Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and PubMed.

  16. What Should You Ask Your Doctor about Kidney Cancer?

    MedlinePlus

    ... Staging What Should You Ask Your Doctor About Kidney Cancer? It’s important to have frank, open discussions ... Ask Your Doctor About Kidney Cancer? More In Kidney Cancer About Kidney Cancer Causes, Risk Factors, and ...

  17. Oxidative stress and autophagy: Crucial modulators of kidney injury

    PubMed Central

    Sureshbabu, Angara; Ryter, Stefan W.; Choi, Mary E.

    2015-01-01

    Both acute kidney injury (AKI) and chronic kidney disease (CKD) that lead to diminished kidney function are interdependent risk factors for increased mortality. If untreated over time, end stage renal disease (ESRD) is an inevitable outcome. Acute and chronic kidney diseases occur partly due to imbalance between the molecular mechanisms that govern oxidative stress, inflammation, autophagy and cell death. Oxidative stress refers to the cumulative effects of highly reactive oxidizing molecules that cause cellular damage. Autophagy removes damaged organelles, protein aggregates and pathogens by recruiting these substrates into double membrane vesicles called autophagosomes which subsequently fuse with lysosomes. Mounting evidence suggests that both oxidative stress and autophagy are significantly involved in kidney health and disease. However, very little is known about the signaling processes that link them. This review is focused on understanding the role of oxidative stress and autophagy in kidney diseases. In this review, we also discuss the potential relationships between oxidative stress and autophagy that may enable the development of better therapeutic intervention to halt the progression of kidney disease and promote its repair and resolution. PMID:25613291

  18. DNA damage caused by inorganic particulate matter on Raji and HepG2 cell lines exposed to ultraviolet radiation.

    PubMed

    Xiao, Michael; Helsing, Albert V; Lynch, Philip M; El-Naggar, Atif; Alegre, Melissa M; Robison, Richard A; O'Neill, Kim L

    2014-09-01

    apoptosis inhibition induced by DNA damage caused by inorganic particulate matter.

  19. Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure.

    PubMed

    Espitia-Pérez, Lyda; Sosa, Milton Quintana; Salcedo-Arteaga, Shirley; León-Mejía, Grethel; Hoyos-Giraldo, Luz Stella; Brango, Hugo; Kvitko, Katia; da Silva, Juliana; Henriques, João A P

    2016-09-15

    Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from "El Cerrejón" (world's largest open-cast coal mine located in Guajira - Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms

  20. Secondary radiation damage as the main cause for unexpected volume effects: A histopathologic study of the parotid gland

    SciTech Connect

    Konings, Antonius W.T. . E-mail: a.w.t.konings@med.umcg.nl; Faber, Hette; Cotteleer, Femmy; Vissink, Arjan; Coppes, Rob P.

    2006-01-01

    Purpose: To elucidate with a histopathological study the mechanism of region-dependent volume effects in the partly irradiated parotid gland of the rat. Methods and Materials: Wistar rats were locally X-irradiated with collimators with conformal radiation portals for 100% volume and 50% cranial/caudal partial volumes. Single doses up to 40 Gy were applied. Parotid saliva samples were collected, and the three lobes of the parotid gland were examined individually on the macro- and micromorphologic level up to 1 year after irradiation. Results: Dose-dependent loss of gland weight was observed 1 year after total or partial X-irradiation. Weight loss of the glands correlated very well with loss of secretory function. Irradiating the cranial 50% volume (implicating a shielded lateral lobe) resulted in substantially more damage in terms of weight loss and loss of secretory function than 50% caudal irradiation (shielding the ventral and dorsal lobe). Histologic examinations of the glands 1 year after irradiation revealed that the shielded lateral lobe was severely affected, in contrast to the shielded ventral and dorsal lobes. Time studies showed that irradiation of the cranial 50% volume caused late development of secondary damage in the shielded lateral lobe, becoming manifest between 240 and 360 days after irradiation. The possible clinical significance of this finding is discussed. Conclusion: It is concluded that the observed region-dependent volume effect for late function loss in the rat parotid gland after partial irradiation is mainly caused by secondary events in the shielded lateral lobe. The most probable first step (primary radiation event) in the development of this secondary damage is radiation exposure to the hilus region (located between the ventral and dorsal lobe). By injuring major excretory ducts and supply routes for blood and nerves in this area, the facility system necessary for proper functioning of the nonexposed lateral lobe is seriously affected

  1. The effect of statins on microalbuminuria, proteinuria, progression of kidney function, and all-cause mortality in patients with non-end stage chronic kidney disease: A meta-analysis.

    PubMed

    Zhang, Zhenhong; Wu, Pingsheng; Zhang, Jiping; Wang, Shunyin; Zhang, Gengxin

    2016-03-01

    Conclusive evidence regarding the effect of statins on non-end stage chronic kidney disease (CKD) has not been reported previously. This meta-analysis evaluated the association between statins and microalbuminuria, proteinuria, progression, and all-cause mortality in patients with non-end stage CKD. Databases (e.g., PubMed, Embase and the Cochrane Library) were searched for randomized controlled trials (RCTs) with data on statins, microalbuminuria, proteinuria, renal health endpoints, and all-cause mortality patients with non-end stage CKD to perform this meta-analysis. The mean difference (MD) of the urine albumin excretion ratios (UAER), 24-h urine protein excretion, and risk ratios (RR) of all-cause mortality and renal health endpoints were calculated, and the results are presented with 95% confidence intervals (CI). A total of 23 RCTs with 39,419 participants were selected. The analysis demonstrated that statins statistically reduced UAER to 26.73 μg/min [95%CI (-51.04, -2.43), Z=2.16, P<0.05], 24-h urine protein excretion to 682.68 mg [95%CI (-886.72, -478.63), Z=6.56, P<0.01] and decreased all-cause mortality [RR=0.78, 95%CI (0.72, 0.84), Z=6.08, P<0.01]. However, the analysis results did not indicate that statins reduced the events of renal health endpoints [RR=0.96, 95%CI (0.91,1.01), Z=1.40, P>0.05]. In summary, our study indicates that statins statistically reduced microalbuminuria, proteinuria, and clinical deaths, but statins did not effectively slow the clinical progression of non-end stage CKD.

  2. Impaired pressure natriuresis resulting in salt-sensitive hypertension is caused by tubulointerstitial immune cell infiltration in the kidney.

    PubMed

    Franco, Martha; Tapia, Edilia; Bautista, Rocio; Pacheco, Ursino; Santamaria, Jose; Quiroz, Yasmir; Johnson, Richard J; Rodriguez-Iturbe, Bernardo

    2013-04-01

    Immune cell infiltration of the kidney is a constant feature in salt-sensitive hypertension (SSHTN). We evaluated the relationship between the renal inflammation and pressure natriuresis in the model of SSHTN that results from transient oral administration of N(ω)-nitro-L-arginine methyl ester (L-NAME). Pressure natriuresis was determined in Wistar rats that received 4 wk of a high-salt (4% NaCl) diet, starting 1 wk after stopping L-NAME, which was administered alone (SSHTN group, n = 17) or in association with mycophenolate mofetil (MMF; MMF group, n = 15). The administration of MMF in association with L-NAME is known to prevent the subsequent development of SSHTN. Control groups received a high (n = 12)- and normal (0.4%)-salt diet (n = 20). Rats with SSHTN had increased expression of inflammatory cytokines and oxidative stress. The severity of hypertension correlated directly (P < 0.0001) with the number of tubulointerstitial immune cells and angiotensin II-expressing cells. Pressure natriuresis was studied at renal arterial pressures (RAPs) of 90, 110, 130, and 150 mmHg. Glomerular filtration rate was similar and stable in all groups, and renal blood flow was decreased in the SSHTN group. Significantly decreased natriuresis (P < 0.05) was found in the SSHTN group at RAPs of 130 and 150 mmHg, and there was an inverse correlation (P < 0.01) between the urinary sodium excretion and the number of tubulointerstitial inflammatory cells (lymphocytes and macrophages) and cells expressing angiotensin II. We conclude that tubulointerstitial inflammation plays a key role in the impairment of pressure natriuresis that results in salt-dependent hypertension in this experimental model.

  3. Kidney Tests

    MedlinePlus

    ... taking out waste products and making urine. Kidney tests check to see how well your kidneys are working. They include blood, urine, and imaging tests. Early kidney disease usually does not have signs ...

  4. Kidney Cancer

    MedlinePlus

    ... common cancers in the United States. Cancer Home Kidney Cancer Language: English Español (Spanish) Recommend on Facebook ... work with the chemical trichloroethylene. What Are the Kidneys? The body has two kidneys, one on each ...

  5. Kidney Problems

    MedlinePlus

    ... our e-newsletter! Aging & Health A to Z Kidney Problems Basic Facts & Information The kidneys are two ... the production of red blood cells. What are Kidney Diseases? For about one-third of older people, ...

  6. Kidney School

    MedlinePlus

    ... copies? Read our licensing agreement Living Successfully with Kidney Disease People with kidney disease can live long ... Listen Printing multiple copies? Read our licensing agreement Kidneys: How They Work, How They Fail, What You ...

  7. Kidney Infection

    MedlinePlus

    ... X-ray called a voiding cystourethrogram. Antibiotics for kidney infections Antibiotics are the first line of treatment ... the infection is completely eliminated. Hospitalization for severe kidney infections For a severe kidney infection, your doctor ...

  8. Polycystic Kidney Disease in the Medaka (Oryzias latipes) pc Mutant Caused by a Mutation in the Gli-Similar3 (glis3) Gene

    PubMed Central

    Hashimoto, Hisashi; Miyamoto, Rieko; Watanabe, Naoki; Shiba, Dai; Ozato, Kenjiro; Inoue, Chikako; Kubo, Yuko; Koga, Akihiko; Jindo, Tomoko; Narita, Takanori; Naruse, Kiyoshi; Ohishi, Kazuko; Nogata, Keiko; Shin-I, Tadasu; Asakawa, Shuichi; Shimizu, Nobuyoshi; Miyamoto, Tomotsune; Mochizuki, Toshio; Yokoyama, Takahiko; Hori, Hiroshi; Takeda, Hiroyuki; Kohara, Yuji; Wakamatsu, Yuko

    2009-01-01

    Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients. PMID:19609364

  9. Water metabolism dysfunction via renin-angiotensin system activation caused by liver damage in mice treated with microcystin-RR.

    PubMed

    Zhong, Qing; Sun, Feng; Wang, Weiguang; Xiao, Wenqing; Zhao, Xiaoni; Gu, Kangding

    2017-03-19

    Microcystins (MCs) are a group of monocyclic heptapeptide toxins that have been shown to act as potent hepatotoxins. However, the observed symptoms of water metabolism disruption induced by microcystin-RR (MC-RR) or MCs have rarely been reported, and a relatively clear mechanism has not been identified. In the present study, male mice were divided into 4 groups (A: 140μg/kg, B: 70μg/kg,C: 35μg/kg, and D: 0μg/kg) and administered MC-RR daily for a month. On day 8 of treatment, an increase in water intake and urine output was observed in the high-dose group compared with the control, and the symptoms worsened with the repeated administration of the toxin until day 30. In addition, the urine specific gravity decreased and serum enzymes that can reflect hepatic damage increased in the high-dose group compared with the control (P<0.05). The mRNA level of angiotensinogen (AGT) in hepatocytes was upregulated to approximately 150% of the control (P<0.05), and the serum renin-angiotensin system (RAS) was activated in the high-dose group; however, signs of renal injury were not observed throughout the experiment. After the toxin treatment was completed, the high levels of the RAS and vasopressin in group A returned to normal levels within 1 week. As expected, the symptoms of polyuria and polydipsia also disappeared. Therefore, we propose that water metabolism dysfunction occurs via RAS activation caused by liver damage because the increased serum RAS levels in the experiment were consistent with the increased urine output and water intake in the mice during the observation period. In addition, we found for the first time that a RAS blocker could alleviate the observed polyuria and polydipsia and inactivate the high level of the RAS induced by MC-RR in a dose-dependent manner, which further supported our hypothesis.

  10. Age-related changes in the function of autophagy in rat kidneys.

    PubMed

    Cui, Jing; Bai, Xue-Yuan; Shi, Suozhu; Cui, Shaoyuan; Hong, Quan; Cai, Guangyan; Chen, Xiangmei

    2012-04-01

    Autophagy is a highly regulated intracellular process for the degradation of cytoplasmic components, especially protein aggregates and damaged organelles. It is essential for maintaining healthy cells. Impaired or deficient autophagy is believed to cause or contribute to aging and age-related disease. In this study, we investigated the effects of age on autophagy in the kidneys of 3-, 12-, and 24-month-old Fischer 344 rats. The results revealed that autophagy-related gene (Atg)7 was significantly downregulated in kidneys of increasing age. The protein expression level of the autophagy marker light chain 3/Atg8 exhibited a marked decline in aged kidneys. The levels of p62/SQSTM1 and polyubiquitin aggregates, representing the function of autophagy and proteasomal degradation, increased in older kidneys. The level of 8-hydroxydeoxyguanosine, a marker of mitochondrial DNA oxidative damage, was also increased in older kidneys. Analysis by transmission electron microscope demonstrated swelling and disintegration of cristae in the mitochondria of aged kidneys. These results suggest that autophagic function decreases with age in the kidneys of Fischer 344 rats, and autophagy may mediate the process of kidney aging, leading to the accumulation of damaged mitochondria.

  11. Population dynamics and damage caused by the leafminer Liriomyza huidobrensis Blanchard (Diptera: Agromyzidae), on seven potato processing varieties grown in temperate environment.

    PubMed

    López, R; Carmona, D; Vincini, A M; Monterubbianesi, G; Caldiz, D

    2010-01-01

    The leafminer Liriomyza huidobrensis Blanchard is considered a key pest for potatoes in Argentina. Population dynamics and leaf damage caused by the leafminer on seven selected potato processing varieties were assessed at Balcarce during the 2002 and 2003 growing seasons. Adult population dynamic was monitored using yellow sticky traps, while leaf damage (punctures and mines) was assessed using a damage index scale from low to severe. Liriomyza huidobrensis adults were present throughout the growing season and the population increased along crop development. The same was true for all varieties regarding larval damage, being low on early crop stages and severe late in the season. Varieties were grouped in two different categories according to damage scale index. Shepody, Kennebec, Frital and Innovator showed a higher damage index when compared with Santana, Ranger Russet and Russet Burbank, which exhibited a lower damage. Moreover, it could be assumed that damage was related to the foliage greenness, with light green colored varieties (Shepody, Kennebec, Frital and Innovator) being more attractive and affected by L. huidobrensis.

  12. D-Amino Acid Substitution of Peptide-Mediated NF-κB Suppression in mdx Mice Preserves Therapeutic Benefit in Skeletal Muscle, but Causes Kidney Toxicity.

    PubMed

    Reay, Daniel P; Bastacky, Sheldon I; Wack, Kathryn E; Stolz, Donna B; Robbins, Paul D; Clemens, Paula R

    2015-05-22

    In Duchenne muscular dystrophy (DMD) patients and the mdx mouse model of DMD, chronic activation of the classical nuclear factor-κB (NF-κB) pathway contributes to the pathogenesis that causes degeneration of muscle fibers, inflammation and fibrosis. Prior studies demonstrate that inhibition of inhibitor of κB kinase (IKK)-mediated NF-κB activation using L-isomer NF-κB essential modulator (NEMO)-binding domain (NBD) peptide-based approaches reduce muscle pathology in the mdx mouse. For our studies, the NBD peptide is synthesized as a fusion peptide with an eight-lysine (8K) protein transduction domain to facilitate intracellular delivery. We hypothesized that the d-isoform peptide could have a greater effect than the naturally occurring L-isoform peptide due to the longer persistence of the D-isoform peptide in vivo. In this study, we compared systemic treatment with low (1 mg/kg) and high (10 mg/kg) doses of L- and D-isomer 8K-wild-type-NBD peptide in mdx mice. Treatment with both L- or D-isoform 8K-wild-type-NBD peptide resulted in decreased activation of NF-κB and improved histology in skeletal muscle of the mdx mouse. However, we observed kidney toxicity (characterized by proteinuria), increased serum creatinine, activation of NF-κB and pathological changes in kidney cortex that were most severe with treatment with the D-isoform of 8K-wild-type-NBD peptide. The observed toxicity was also seen in normal mice.

  13. Inhibitory effect and cell damage on bacterial flora of fish caused by chitosan, nisin and sodium lactate.

    PubMed

    Schelegueda, Laura Inés; Zalazar, Aldana Lourdes; Gliemmo, María Fernanda; Campos, Carmen Adriana

    2016-02-01

    The effect of the combined use of chitosan, nisin and sodium lactate on the growth of Listeria innocua, Shewanella putrefaciens and psychrophilic bacteria isolated from fish was investigated in broth by means of minimum inhibitory concentrations (MIC). Furthermore, the sites of cell-injury caused by mentioned antimicrobials and their combinations on L. innocua and S. putrefaciens were studied. MIC of antimicrobial mixtures were evaluated by Berembaum design and check board method. Antimicrobials' sites of injury were investigated by the evaluation of cell constituents' release, cell surface hydrophobicity and differential scanning calorimetry. Results depended on antimicrobial used; several combinations inhibited the growth of L. innocua and S. putrefaciens and all combinations inhibited psychrophilic bacteria. Besides, some mixtures showed synergistic effects. All the mixtures affected ribosomes and DNA of the studied bacteria. Regarding cellular envelope, antimicrobials acted according to the structural characteristics of target microorganisms. Cell damage was higher when antimicrobials were combined, which could explain the observed synergistic effects. This study demonstrates and justifies the synergistic action of chitosan, nisin and sodium lactate on the inhibition of microorganisms related to fish spoilage and remarks the promissory use of the synergic combination of antimicrobials for fish preservation.

  14. Endogenous salicylic acid protects rice plants from oxidative damage caused by aging as well as biotic and abiotic stress.

    PubMed

    Yang, Yinong; Qi, Min; Mei, Chuansheng

    2004-12-01

    Salicylic acid (SA) is a key endogenous signal that mediates defense gene expression and disease resistance in many dicotyledonous species. In contrast to tobacco and Arabidopsis, which contain low basal levels of SA, rice has two orders of magnitude higher levels of SA and appears to be insensitive to exogenous SA treatment. To determine the role of SA in rice plants, we have generated SA-deficient transgenic rice by expressing the bacterial salicylate hydroxylase that degrades SA. Depletion of high levels of endogenous SA in transgenic rice does not measurably affect defense gene expression, but reduces the plant's capacity to detoxify reactive oxygen intermediates (ROI). SA-deficient transgenic rice contains elevated levels of superoxide and H2O2, and exhibits spontaneous lesion formation in an age- and light-dependent manner. Exogenous application of SA analog benzothiadiazole complements SA deficiency and suppresses ROI levels and lesion formation. Although an increase of conjugated catechol was detected in SA-deficient rice, catechol does not appear to significantly affect ROI levels based on the endogenous catechol data and exogenous catechol treatment. When infected with the blast fungus (Magnaporthe grisea), SA-deficient rice exhibits increased susceptibility to oxidative bursts elicited by avirulent isolates. Furthermore, SA-deficient rice is hyperresponsive to oxidative damage caused by paraquat treatment. Taken together, our results strongly suggest that SA plays an important role to modulate redox balance and protect rice plants from oxidative stress.

  15. Docosahexaenoic Acid Reduces Cerebral Damage and Ameliorates Long-Term Cognitive Impairments Caused by Neonatal Hypoxia-Ischemia in Rats.

    PubMed

    Arteaga, Olatz; Revuelta, M; Urigüen, L; Martínez-Millán, L; Hilario, E; Álvarez, A

    2016-10-29

    As the interest in the neuroprotective possibilities of docosahexaenoic acid (DHA) for brain injury has grown in the recent years, we aimed to investigate the long-term effects of this fatty acid in an experimental model of perinatal hypoxia-ischemia in rats. To this end, motor activity, aspects of learning, and memory function and anxiety, as well as corticofugal connections visualized by using tracer injections, were evaluated at adulthood. We found that in the hours immediately following the insult, DHA maintained mitochondrial inner membrane integrity and transmembrane potential, as well as the integrity of synaptic processes. Seven days later, morphological damage at the level of the middle hippocampus was reduced, since neurons and myelin were preserved and the astroglial reactive response and microglial activation were seen to be diminished. At adulthood, the behavioral tests revealed that treated animals presented better long-term working memory and less anxiety than non-treated hypoxic-ischemic animals, while no difference was found in the spontaneous locomotor activity. Interestingly, hypoxic-ischemic injury caused alterations in the anterograde corticofugal neuronal connections which were not so evident in rats treated with DHA. Thus, our results indicate that DHA treatment can lead to long-lasting neuroprotective effects in this experimental model of neonatal hypoxia-ischemic brain injury, not only by mitigating axonal changes but also by enhancing cognitive performance at adulthood.

  16. Announcement: National Kidney Month - March 2017.

    PubMed

    2017-03-03

    Each year, March is designated National Kidney Month to raise awareness about the prevention and early detection of kidney disease. In the United States, kidney disease is the ninth leading cause of death (1). Approximately one in seven (15%) U.S. adults aged ≥20 years are estimated to have chronic kidney disease, most of whom are unaware of their condition (2). If left untreated, chronic kidney disease can lead to kidney failure, requiring dialysis or transplantation for survival (3).

  17. Upper gastrointestinal bleeding as a risk factor for dialysis and all-cause mortality: a cohort study of chronic kidney disease patients in Taiwan

    PubMed Central

    Liang, Chih-Chia; Chang, Chiz-Tzung; Wang, I-Kuan; Huang, Chiu-Ching

    2016-01-01

    Objective Impaired renal function is associated with higher risk of upper gastrointestinal bleeding (UGIB) in patients with chronic kidney disease and not on dialysis (CKD-ND). It is unclear if UGIB increases risk of chronic dialysis. The aim of the study was to investigate risk of chronic dialysis in CKD-ND patients with UGIB. Setting All CKD-ND stage 3–5 patients of a CKD programme in one hospital between 2003 and 2009 were enrolled and prospectively followed until September 2012. Primary and secondary outcome measures Chronic dialysis (dialysis for more than 3 months) started and all-cause mortality. The risk of chronic dialysis was analysed using Cox proportional hazard regression with adjustments for age, gender and renal function, followed by competing-risks analysis. Results We analysed 3126 CKD-ND patients with a mean age of 65±14 years for 2.8 years. Of 3126 patients, 387 (12.4%) patients developed UGIB, 989 (31.6%) patients started chronic dialysis and 197 (6.3%) patients died. UGIB increased all-cause mortality (adjusted HR (aHR): 1.51, 95% CI 1.07 to 2.13) and the risk of chronic dialysis (aHR; 1.29, 95% CI 1.11 to 1.50). The subdistribution HR (SHR) of UGIB for chronic dialysis (competing event: all-cause mortality) was 1.37 (95% CI 1.15 to 1.64) in competing-risks analysis with adjustments for age, renal function, gender, diabetes, haemoglobin, albumin and urine protein/creatinine ratio. Conclusions UGIB is associated with increased risk of chronic dialysis and all-cause mortality in patients with CKD-ND stages 3–5. This association is independent of age, gender, basal renal function, haemoglobin, albumin and urine protein levels. PMID:27150184

  18. A review of the impact of oxidative stress and some antioxidant therapies on renal damage.

    PubMed

    Tamay-Cach, F; Quintana-Pérez, J C; Trujillo-Ferrara, J G; Cuevas-Hernández, R I; Del Valle-Mondragón, L; García-Trejo, E M; Arellano-Mendoza, M G

    2016-01-01

    An increase in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to complications during chronic kidney disease (CKD). This increase essentially derives from the impairment of natural antioxidant systems of the organism. The resulting oxidative stress produces damage to kidney tissue, especially by affecting nephrons and more generally by disrupting the function and structure of the glomerulus and interstitial tubule. This leads to a rapid decline in the condition of the patient and finally renal failure. Possible causes of kidney tissue damage are explored, as are different therapies, especially those related to the administration of antioxidants.

  19. The cause of heavy damage concentration in downtown Mashiki inferred from observed data and field survey of the 2016 Kumamoto earthquake

    NASA Astrophysics Data System (ADS)

    Kawase, Hiroshi; Matsushima, Shinichi; Nagashima, Fumiaki; Baoyintu; Nakano, Kenichi

    2017-01-01

    To understand the cause of heavy structural damage during the mainshock (on April 16, 2016) of the 2016 Kumamoto earthquake sequence, we carried out a field survey from April 29 through May 1, 2016, in Mashiki where heavy damage concentration was observed. The heavy damage concentration in downtown Mashiki could be understood based on the observed strong motions with the Japan Meteorological Agency instrumental seismic intensity of VII and information collected by the field investigation. First, the fundamental features of the structural damage in downtown Mashiki were summarized. Then, a distribution map of peak frequencies was derived from horizontal-to-vertical spectral ratios of microtremors. We could not see any systematic correlation between the peak frequencies and spatial distribution of damage ratios. We also analyzed observed strong motion data at two sites to obtain fling-step-like motions in the displacement time histories through the double integration of unfiltered accelerograms. It turned out that at both strong motion observation sites in Mashiki, only the east-west (EW) components had very strong velocity pulses westward before the emergence of the fling-step-like motion eastward, which would be the primary cause of heavy structural damage in downtown Mashiki, not site effects nor the fling-step-like motion itself.

  20. Heavy metals, arsenic, and pesticide contamination in an area with high incidence of chronic kidney disease of non-traditional causes in El Salvador

    NASA Astrophysics Data System (ADS)

    Lopez, D. A.; Ribó, A.; Quinteros, E.; Mejia, R.; Jovel, R.; VanDervort, D.; Orantes, C. M.

    2013-12-01

    Chronic kidney disease of non-traditional causes is epidemic in Central America, Southern Mexico and other regions of the world such as Sri Lanka, where the origin of the illness is attributed to exposure to agrochemicals and arsenic in soils and groundwater. In Central America, several causes have been suggested for this illness including: high ambient temperatures and chronic dehydration, and toxic effects of agrochemicals. Previous research using step-wise multivariate regression in El Salvador found statistically significant correlation between the spatial distribution of the number of sick people per thousand inhabitants and the percent area cultivated with sugar cane, cotton, and beans, and maximum ambient temperature, with sugar cane cultivation as the most significant factor. This study aims to investigate the possible effects of agricultural activities in the occurrence of this illness looking at heavy metal, arsenic and pesticide contamination in soil, water and sediments of a community located in Bajo Lempa region (Ciudad Romero, El Salvador) and heavily affected by this illness. The Bajo Lempa region is close to Lempa River delta, in the Pacific coast. Ground and surface water, sediment and soil samples were collected in the village where the patients live and in the agricultural areas where they work. With respect to the heavy metals, lead and cadmium where detected in the soils but below the standards for cultivated soils, however, they were not detected in the majority of surface and groundwater. Of the inorganic contaminants, arsenic was present in most soil, sediments, and water samples with some concentrations considerable higher than the standards for cultivated lands and drinking water. Statistically different concentrations in soils were found for the village soils and the cultivated soils, with arsenic higher in the cultivated soils. For the pesticides, results show a significant pollution of soil and groundwater of organochlorine pesticides

  1. Kidney-lung pathophysiological crosstalk: its characteristics and importance.

    PubMed

    Domenech, Pilar; Perez, Tomas; Saldarini, Agustina; Uad, Pedro; Musso, Carlos G

    2017-04-11

    Crosstalk between the lung and the kidney is based on the similarities that these organs share. This is why different diseases that affect one organ can have repercussions on the other. Patients with acute kidney injury can present complications such as pulmonary edema and require mechanical ventilation in respiratory failure. This interaction occurs due to the increase in systemic immune mediators that cause inflammatory reactions, oxidative stress, and an increase in vascular permeability in the lung. With regard to lung-induced renal damage, the kidney can also be affected by chemical mediators, which are translocated into the bloodstream. Moreover, the kidneys are extremely sensitive to oxygen changes which can cause them to lose their autoregulation mechanism. In patients with acute lung injury (ALI), oxygen supply is decreased causing renal hypoxia. Besides, hypercapnia generated by ALI causes vasoconstriction in the renal vascular network and activation of the renal angiotensin aldosterone system. ALI not only can cause renal injury, but also worsening chronic obstructive pulmonary disease and obstructive sleep apnea. In conclusion, kidney-lung crosstalk is commonly present in certain pathological states, and knowing its characteristics is crucial for managing the complications which may arise from this vicious circle.

  2. Damage and loss assessment on rubber trees caused by typhoon based on high-precision remote sensing data and field investigation

    NASA Astrophysics Data System (ADS)

    Li, Jian; Fang, Weihua; Tan, Chenyan

    2016-04-01

    Forest dynamics are highly relevant to land hydrology, climate, carbon budget and biodiversity. Damage and loss assessment of forest caused by typhoon is essential to the understanding of ecosystem variations. Combination of high-precision remote sensing data and field investigation is critical to the assessment of forest damage loss. In this study, high-precision remote sensing data prior to and after typhoon from IKONOS, QuickBird, unmanned aerial vehicle (UAV) are used for identifying rubber tree disturbance. The ground truth data of rubber tree damage collected through field investigation are used to verify and compare the results. Taken the forest damage induced by typhoon Rammasun (201409) in Hainan as an example, 5 damage types (overthrown, trunk snapped below 2m, trunk snapped above 2m, half-overthrown, and sheared) of rubber trees are clearly interpreted compared with field investigation results. High-precision remote sensing data is then applied to other areas to evaluate the forest damage severity. At last, rubber tree damage severity is investigated with other typhoon hazard factors such as wind, topography, soil and precipitation.

  3. An Experimental and Theoretical Study of Asymmetric Earthquake Rupture Propagation Caused by Off-Fault Fracture Damage

    NASA Astrophysics Data System (ADS)

    Bhat, H.; Sammis, C. G.; Rosakis, A.

    2010-12-01

    The interaction between a dynamic mode II fracture on a fault plane and off-fault damage has been studied experimentally using high-speed photography and theoretically using finite element numerical simulations. In the experimental studies, fracture damage was created in photoelastic Homalite plates by thermal shock in liquid nitrogen and rupture velocities were measured by imaging fringes at the tips. Two cases were studied: an interface between damaged and undamaged Homalite plates, and an interface between damaged Homalite and undamaged polycarbonate plates. Propagation on the interface between damaged and undamaged Homalite is asymmetric. A ruptures propagating in the direction for which the compressional lobe of its crack-tip stress field is in the damage (which we term the ‘C’ direction) is unaffected by the damage. In the opposite ‘T’ direction, the rupture velocity is significantly slower than the velocity in undamaged plates at the same load. Specifically, transitions to supershear observed using undamaged plates are not observed in the ‘T’ direction. Propagation on the interface between damaged Homalite and undamaged polycarbonate exhibits the same asymmetry, even though the elastically “favored” ‘+’ direction coincides with the ‘T’ direction in this case indicating that the effect of damage is stronger than the effect of elastic asymmetry. This asymmetric propagation was also simulated numerically by incorporating the micromechanical damage mechanics formulated by Ashby and Sammis (PAGEOPH, 1990) into the ABAQUS dynamic finite element code. The quasi-static Ashby/Sammis formulation has been improved to include modern concepts of dynamic fracture mechanics, which become important at the high loading rates in the process zone of a propagating rupture.

  4. Identification of personal lubricants that can cause rectal epithelial cell damage and enhance HIV type 1 replication in vitro.

    PubMed

    Begay, Othell; Jean-Pierre, Ninochka; Abraham, Ciby J; Chudolij, Anne; Seidor, Samantha; Rodriguez, Aixa; Ford, Brian E; Henderson, Marcus; Katz, David; Zydowsky, Thomas; Robbiani, Melissa; Fernández-Romero, José A

    2011-09-01

    Over-the-counter personal lubricants are used frequently during vaginal and anal intercourse, but they have not been extensively tested for biological effects that might influence HIV transmission. We evaluated the in vitro toxicity anti-HIV-1 activity and osmolality of popular lubricants. A total of 41 lubricants were examined and compared to Gynol II and Carraguard as positive and negative controls for toxicity, respectively. Cytotoxicity was assessed using the XTT assay. The MAGI assay with R5 and X4 HIV-1 laboratory strains was used to evaluate antiviral activity. The effect of the lubricants on differentiated Caco-2 cell monolayers (transepithelial electrical resistance, TEER) was also measured. None of the lubricants tested showed significant activity against HIV-1. Surprisingly, four of them, Astroglide Liquid, Astroglide Warming Liquid, Astroglide Glycerin & Paraben-Free Liquid, and Astroglide Silken Secret, significantly enhanced HIV-1 replication (p<0.0001). A common ingredient in three of these preparations is polyquaternium-15. In vitro testing of a chemically related compound (MADQUAT) confirmed that this similarly augmented HIV-1 replication. Most of the lubricants were found to be hyperosmolar and the TEER value dropped approximately 60% 2 h after exposure to all lubricants tested. Cells treated with Carraguard, saline, and cell controls maintained about 100% initial TEER value after 2-6 h. We have identified four lubricants that significantly increase HIV-1 replication in vitro. In addition, the epithelial damage caused by these and many other lubricants may have implications for enhancing HIV transmission in vivo. These data emphasize the importance of performing more rigorous safety testing on these products.

  5. Identification of Personal Lubricants That Can Cause Rectal Epithelial Cell Damage and Enhance HIV Type 1 Replication in Vitro

    PubMed Central

    Begay, Othell; Jean-Pierre, Ninochka; Abraham, Ciby J.; Chudolij, Anne; Seidor, Samantha; Rodriguez, Aixa; Ford, Brian E.; Henderson, Marcus; Katz, David; Zydowsky, Thomas; Robbiani, Melissa

    2011-01-01

    Abstract Over-the-counter personal lubricants are used frequently during vaginal and anal intercourse, but they have not been extensively tested for biological effects that might influence HIV transmission. We evaluated the in vitro toxicity anti-HIV-1 activity and osmolality of popular lubricants. A total of 41 lubricants were examined and compared to Gynol II and Carraguard as positive and negative controls for toxicity, respectively. Cytotoxicity was assessed using the XTT assay. The MAGI assay with