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Sample records for renal toxicity compared

  1. Low renal toxicity of lipoplatin compared to cisplatin in animals.

    Science.gov (United States)

    Devarajan, Prasad; Tarabishi, Ridwan; Mishra, Jaya; Ma, Qing; Kourvetaris, Andreas; Vougiouka, Maria; Boulikas, Teni

    2004-01-01

    Cisplatin is one of the most widely used and effective chemotherapeutic agents for the treatment of several human malignancies. Although the effectiveness of cisplatin is high, its toxicities justify the demand for improved formulations of this drug. A liposomal formulation of cisplatin, Lipoplatin, was developed in order to reduce the systemic toxicity of cisplatin. Mice and rats injected with cisplatin developed renal insufficiency with clear evidence of tubular damage, but those injected with the same dose of Lipoplatin were almost completely free of kidney injury. The maximum levels of total platinum in rat kidneys after intraperitoneal bolus injection of cisplatin or Lipoplatin at similar doses were similar, but the steady state accumulation of total platinum in the kidney was 5 times higher for cisplatin compared to Lipoplatin. This is proposed as one mechanism to explain the low renal toxicity of Lipoplatin.

  2. Comparative effects of chelating agents on distribution, excretion, and renal toxicity of gold sodium thiomalate in rats.

    Science.gov (United States)

    Takahashi, Y; Funakoshi, T; Shimada, H; Kojima, S

    1994-05-31

    The effects of various chelating agents, such as (2S)-1-(3-mercaptopropionyl)-L-proline (captopril), N-(2-mercaptopropionyl)-glycine (tiopronin), L-cysteine (L-Cys), D-cysteine (D-Cys), N-acetyl-L-cysteine (L-NAC), N-benzyl-D-glucamine dithiocarbamate (BGD), and ethylenediaminetetraacetate (EDTA), on the distribution, excretion, and renal toxicity of gold sodium thiomalate (AuTM) in rats were investigated. Rats were intraperitoneally injected with the chelating agents (1.2 mmol/kg each) immediately after intravenous injection of AuTM (0.026 mmol/kg). Treatment with captopril or tiopronin significantly prevented increases in the urinary excretion of protein, aspartate aminotransferase (AST), and glucose and the blood urea nitrogen (BUN) level after AuTM injection. L-NAC and D-Cys significantly prevented increases in the urinary excretion of protein, AST, and glucose after AuTM injection, but did not reduce to control levels. Treatment with BGD, EDTA, or L-Cys did not prevent AuTM-induced increases in the urinary excretion of protein, AST, and glucose and BUN level. Tiopronin significantly increased the urinary excretion of gold. Captopril slightly promoted both the urinary and fecal excretion of gold, resulting in the significant increase in the total excretion of the metal. Tiopronin and captopril significantly decreased the gold concentration in the kidney and liver. L-Cys, D-Cys, L-NAC, BGD, and EDTA had no significant effect on the excretion or distribution of gold at 7 days after AuTM injection. These results indicate that tiopronin and captopril can ameliorate the renal toxicity induced by AuTM. In addition, the comparative effects of 2,3-dimercaptopropane sulfonate (DMPS), N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine), captopril, and tiopronin at various dose levels (1.2, 0.4 or 0.2 mmol/kg) on the distribution and renal toxicity of gold were studied. DMPS was effective in removing gold from the kidney and in protecting against the renal toxicity

  3. Renal Toxicities of Targeted Therapies.

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    Abbas, Anum; Mirza, Mohsin M; Ganti, Apar Kishor; Tendulkar, Ketki

    2015-12-01

    With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.

  4. [Renal toxicity of antiviral drugs].

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    Frasca', Giovanni M; Balestra, Emilio; Tavio, Marcello; Morroni, Manrico; Manarini, Gloria; Brigante, Fabiana

    2012-01-01

    Highly effective and powerful antiviral drugs have been introduced into clinical practice in recent years which are associated with an increased incidence of nephrotoxicity. The need of combining several drugs, the fragility of the patients treated, and the high susceptibility of the kidney are all factors contributing to renal injury. Many pathogenetic mechanisms are involved in the nephrotoxicity of antiviral drugs, including drug interaction with transport proteins in the tubular cell; direct cytotoxicity due to a high intracellular drug concentration; mitochondrial injury; and intrarenal obstruction or stone formation due to the low solubility of drugs at a normal urinary pH. As a result, various clinical pictures may be observed in patients treated with antiviral drugs, ranging from tubular dysfunction (Fanconi syndrome, renal tubular acidosis, nephrogenic diabetes insipidus) to acute renal failure (induced by tubular necrosis or crystal nephropathy) and kidney stones. Careful attention should be paid to prevent renal toxicity by evaluating the glomerular filtration rate before therapy and adjusting the drug dosage accordingly, avoiding the combination with other nephrotoxic drugs, and monitoring renal parameters on a regular basis while treating patients.

  5. Renal toxicity of the anticancer drug fostriecin

    NARCIS (Netherlands)

    de Vries, EGE; Meijer, S; Mulder, NH; de Jong, Paul; de Jong, Robert

    Purpose: Fostriecin is an inhibitor of topoisomerase II catalytic activity. In a phase I trial we observed renal toxicity, documented as a rise in serum creatinine, which was reversible and non-dose-limiting. The purpose of this study was a detailed analysis of this toxicity. Methods: A total of 20

  6. Toxicity of uranium on renal cells

    Energy Technology Data Exchange (ETDEWEB)

    Thiebault, C.; Carriere, M.; Gouget, B. [CEA Saclay, CNRS, UMR9956, Lab Pierre Sue, F-91191 Gif Sur Yvette, (France)

    2007-07-01

    Kidney and bone are the main retention organs affected by uranium toxicity. Although the clinical effects of uranium poisoning are well known, only few studies dealt with cellular mechanisms of toxicity. The purpose of this study was to investigate the cyto- and genotoxicity of uranium (U) on renal cells. The cell death was also studied in this conditions of exposure. The effects of U were evaluated in acute and chronic exposure. The acute effects were evaluated after 24 h exposure to strong U concentrations (200-700{mu}M). The chronic exposure was observed on renal cells incubated with low U concentrations (0.1-100 {mu}M) until 70 days then with high uranium concentrations (400-500 {mu}M) during 24 h. U induces apoptosis cell death mainly by the intrinsic pathway. The high U concentrations (600-700 {mu}M) lead to necrosis. U induces DNA damages (single, double strand breaks, as well as alkali labile sites) from 300{mu}M. The cytotoxicity and intracellular accumulation of uranium were less important in cells previously exposed to low uranium concentrations when compared to non-exposed cells. In the same time, DNA damage observed after acute exposure of uranium decreased with the increase of chronic uranium concentrations. These results suggest that renal cells became resistant to uranium, probably due to a cellular transformation process. In conclusion, high U concentrations (300-700{mu}M) induce apoptosis cell death and DNA damages. Cells previously exposed to low U concentrations present also DNA damages and a cellular transformation. (authors)

  7. Erdosteine against acetaminophen induced renal toxicity.

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    Isik, Bunyamin; Bayrak, Reyhan; Akcay, Ali; Sogut, Sadik

    2006-07-01

    Acetaminophen (APAP) induced toxicities have been a major problem in clinical practice. The aim of the present study was to demonstrate a possible protective role of erdosteine, a mucolytic agent having antioxidant properties via its active metabolites, on APAP induced renal damage in rats. Female Wistar Albino rats were divided into groups including control, erdosteine (150 mg/kg, oral), APAP (1 g/kg, oral) APAP+erdosteine (150 mg/kg, oral) and APAP+erdosteine (300 mg/kg, oral). APAP treatment caused lipid peroxidation as well as high NO level in renal tissue. Also, APAP treated rats had decreased activities of CAT and GSH-Px, but not SOD. In addition, tubular epithelial degeneration, vacuolization and cell desquamation were clearly observed in the APAP treated rats. The cellular debris in the proximal tubules and cortical interstitial congestions were prominent in the kidneys of APAP treated rats. BUN and creatinine levels were increased after APAP administration. All these pathological changes were reversed after erdosteine treatments. Erdosteine treated APAP groups showed milder tubular degeneration, epithelial vacuolization in the proximal tubules, lesser cellular desquamation and better morphology when compared with APAP groups. In conclusion, erdosteine may be a choice of preventive treatment against APAP induced nephrotoxicity.

  8. Comparing toxic air pollutant programs

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, S.C. [ECKENFELDER Inc., Greenville, SC (United States)

    1997-05-01

    This article compares state and federal toxic air pollutant programs. The Clean Air Act Ammendments created a program for the control of Hazardous Air Pollutants based on the establishment of control technology standards. State toxic programs can be classified into two categories: control technology-based and ambient concentration-based. Many states have opened to implement the MACT standards while enforcing their own state air toxics programs. Specific topics discussed include the following: the Federal air toxics program; existing state regulations; New Jersey Air Toxic Program; New York Toxics program.

  9. Myoclonus in renal failure: Two cases of gabapentin toxicity

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    Kenneth R. Kaufman

    2014-01-01

    Full Text Available Gabapentin, an AED approved for the adjunctive treatment of partial seizures with/without secondary generalization and for the treatment of postherpetic neuralgia, is frequently used off-label for the treatment of both psychiatric and pain disorders. Since gabapentin is cleared solely by renal excretion, dosing requires consideration of the patient's renal function. Myoclonic activity may occur as a complication of gabapentin toxicity, especially with acute kidney injury or end-stage renal disease. We report 2 cases of myoclonic activity associated with gabapentin toxicity in the setting of renal disease which resolved with discontinuation of gabapentin and treatment with hemodialysis and peritoneal dialysis. As gabapentin has multiple indications and off-label uses, an understanding of myoclonus, neurotoxicity, and renal dosing is important to clinicians in multiple specialties.

  10. A comparative study on renal biopsy before and after long-term calcineurin inhibitors therapy: an insight for pathogenesis of its toxicity.

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    Singh, Lavleen; Singh, Geetika; Sharma, Alok; Sinha, Aditi; Bagga, Arvind; Dinda, A K

    2015-01-01

    Calcineurin inhibitors (CNIs) are effective immunosuppressive agents for the successful treatment of childhood steroid-resistant nephrotic syndrome (SRNS). Because these patients require long-term treatment, the identification of early markers of CNI-induced nephrotoxicity (CNIN) is imperative. The monitoring of CNI trough levels, serum creatinine, and glomerular filtration rate is not an accurate marker of CNIN. The present study has been undertaken to identify early markers of CNIN in SRNS patients. Twenty-four pediatric SRNS patients were included with paired renal biopsies, before initiation (time zero biopsy) and at least 1 year after CNI therapy (protocol renal biopsy) with standard dosage. Semiquantitative morphologic grading of the histologic features was done for assessing CNIN. Immunohistochemical markers for oxidative stress (nitrotyrosine [NT]), fibrogenic cytokine (transforming growth factor β1 [TGF-β1]), and endothelial injury (endothelial nitric oxide synthase [eNOS]) were evaluated. In addition, ultrastructural study was done to assess mitochondrial injury in endothelial and tubular epithelial cells. The protocol renal biopsies in comparison with time zero biopsies showed significant increase in glomerulosclerosis, juxtaglomerular apparatus hyperplasia, tubular atrophy, interstitial fibrosis, arteriolar hyalinosis, and smooth muscle vacuolization (P biopsies. Mean mitochondrial injury grade among post-CNI cases in endothelial cells and proximal tubular cells was 2.28 and 1.4, whereas in pre-CNI, it was 0.28 and 0.27, respectively. We propose that immunohistochemical overexpression of NT, eNOS, and TGF-β1 is an early marker of CNIN. Endothelial and proximal tubular mitochondrial injury may play an important role in the pathogenesis of CNIN.

  11. A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

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    Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

    2017-01-01

    Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

  12. In Vivo Renal Clearance, Biodistribution, Toxicity of Gold nanoclusters

    CERN Document Server

    Zhang, Xiao-Dong; Shen, Xiu; Liu, Pei-Xun; Fan, Fei-Yue; Fan, Sai-Jun; 10.1016/j.biomaterials.2012.03.020

    2012-01-01

    Gold nanoparticles have shown great prospective in cancer diagnosis and therapy, but they can not be metabolized and prefer to accumulate in liver and spleen due to their large size. The gold nanoclusters with small size can penetrate kidney tissue and have promise to decrease in vivo toxicity by renal clearance. In this work, we explore the in vivo renal clearance, biodistribution, and toxicity responses of the BSA- and GSH-protected gold nanoclusters for 24 hours and 28 days. The BSA-protected gold nanoclusters have low-efficient renal clearance and only 1% of gold can be cleared, but the GSH-protected gold nanoclusters have high-efficient renal clearance and 36 % of gold can be cleared after 24 hours. The biodistribution further reveals that 94% of gold can be metabolized for the GSH-protected nanoclusters, but only less than 5% of gold can be metabolized for the BSA-protected nanoclusters after 28 days. Both of the GSH- and BSA-protected gold nanoclusters cause acute infection, inflammation, and kidney fu...

  13. Cellular localization of uranium in the renal proximal tubules during acute renal uranium toxicity.

    Science.gov (United States)

    Homma-Takeda, Shino; Kitahara, Keisuke; Suzuki, Kyoko; Blyth, Benjamin J; Suya, Noriyoshi; Konishi, Teruaki; Terada, Yasuko; Shimada, Yoshiya

    2015-12-01

    Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium levels were maintained up to 8 days post-administration, despite more rapid reductions in mean renal concentration. Two weeks after uranium administration, damaged areas were filled with regenerating tubules and morphological signs of tissue recovery, but areas of high uranium concentration (100-fold above mean renal concentration) were still found in the epithelium of regenerating tubules. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segment of the proximal tubules and retention of uranium in concentrated areas during recovery are characteristics of uranium behavior in the kidney.

  14. [The acute renal and cerebral toxicity of lithium: a cerebro-renal syndrome? A case report].

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    Prencipe, M; Cicchella, A; Del Giudice, A; Di Giorgio, A; Scarlatella, A; Vergura, M; Aucella, F

    2013-01-01

    This descriptive report describes the case of a 50 year-old woman with bipolar disorder, whose maintenance therapy comprised risperidone, sodium valproato and lithium carbonate without any past occurrence of toxicity. Her past medical history was significant for hypertension, cardiopathy and obesity. She presented with a 1-week history of fever, increasing confusion and slurred speech. At presentation, the patient was somnolent. Laboratory investigations revealed a serum creatinine of 3,6 mg/dl, BUN 45 mg/dl serum lithium 3,0 mEq/L with polyuria defined as more than 3 litres a day. EEG and ECG were abnormal. CT brain scanning and lumbar puncture were negative for brain haemorrage or infection. Lithium toxicity causes impairment of renal concentration and encephalopathy due to lithium recirculation, a mechanism responsible for the so-called cerebro-renal syndrome, where dialysis plays an important role in treatment.The patient was treated with continous veno-venous haemodiafiltration (CVVHDF) over 35 hours with gradual improvement of her general condition and efficacy of renal concentration. Our case highlights a few important points. Lithium nefrotoxicity and neurotoxicity can cause a cerebro-renal syndrome even when serum lithium levels are not particularly raised (2,5-3,5 mEq/L). Haemodialysis is the treatment of choice to reduce the molecular mechanisms of lithium-related changes in urinary concentration and reinstate dopaminergic activity in the brain.

  15. Drug administration in patients with renal insufficiency. Minimising renal and extrarenal toxicity.

    Science.gov (United States)

    Matzke, G R; Frye, R F

    1997-03-01

    Renal insufficiency has been associated with an increased risk of adverse effects with many classes of medications. The risk of some, but not all, adverse effects has been linked to the patient's degree of residual renal function. This may be the result of inappropriate individualisation of those agents that are primarily eliminated by the kidney, or an alteration in the pharmacodynamic response as a result of renal insufficiency. The pathophysiological mechanism responsible for alterations in drug disposition, especially metabolism and renal excretion, is the accumulation of uraemic toxins that may modulate cytochrome P450 enzyme activity and decrease glomerular filtration as well as tubular secretion. The general principles to enhance the safety of drug therapy in patients with renal insufficiency include knowledge of the potential toxicities and interactions of the therapeutic agent, consideration of possible alternatives therapies and individualisation of drug therapy based on patient level of renal function. Although optimisation of the desired therapeutic outcomes are of paramount importance, additional pharmacotherapeutic issues for patients with reduced renal function are the prevention or minimisation of future acute or chronic nephrotoxic insults, as well as the severity and occurrence of adverse effects on other organ systems. Risk factors for the development of nephrotoxicity for selected high-risk therapies (e.g. aminoglycosides, nonsteroidal anti-inflammatory drugs, ACE inhibitors and radiographic contrast media) are quite similar and include pre-existing renal insufficiency, concomitant administration of other nephrotoxins, volume depletion and concomitant hepatic disease or congestive heart failure. Investigations of prophylactic approaches to enhance the safety of these agents in patients with renal insufficiency have yielded inconsistent outcomes. Hydration with saline prior to drug exposure has given the most consistent benefit, while sodium

  16. Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney

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    Ayodele Jacob Akinyemi

    2017-04-01

    Full Text Available In this study, the effect of enzymes involved in degradation of renal adenosine and l-arginine was investigated in rats exposed to cadmium (Cd and treated with curcumin, the principal active phytochemical in turmeric rhizome. Animals were divided into six groups (n = 6: saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. The results of this study revealed that the activities of renal adenosine deaminase and arginase were significantly increased in Cd-treated rats when compared with the control (p < 0.05. However, co-treatment with curcumin inhibits the activities of these enzymes compared with Cd-treated rats. Furthermore, Cd intoxication increased the levels of some renal biomarkers (serum urea, creatinine, and electrolytes and malondialdehyde level with a concomitant decrease in functional sulfhydryl group and nitric oxide (NO. However, co-treatment with curcumin at 12.5 mg/kg and 25 mg/kg, respectively, increases the nonenzymatic antioxidant status and NO in the kidney, with a concomitant decrease in the levels of malondialdehyde and renal biomarkers. Therefore, our results reinforce the importance of adenosine deaminase and arginase activities in Cd poisoning conditions and suggest some possible mechanisms of action by which curcumin prevent Cd-induced renal toxicity in rats.

  17. A renal-targeted triptolide aminoglycoside (TPAG) conjugate for lowering systemic toxicities of triptolide.

    Science.gov (United States)

    Qi, Bowen; Wang, Xinyi; Zhou, Yangyang; Han, Qiao; He, Ling; Gong, Tao; Sun, Xun; Fu, Yao; Zhang, Zhirong

    2015-06-01

    Triptolide (TP), a naturally derived compound, is proven effective in the treatment of nephritis and chronic allograft nephropathy. However, the severe multiorgan toxicity greatly limited it from further clinic use. 2-Glucosamine was demonstrated as a potential targeting ligand that could specifically interact with megalin receptors highly expressed in renal proximal tubules. In this study, 2-glucosamine was employed as a glycosyl donor while triptolide the acceptor to afford a nonhydrolyzable triptolide derivative-triptolide aminoglycoside (TPAG). The kidney-targeting efficiency, pharmacodynamic properties and safety of TPAG were thus evaluated. TPAG displayed 6.94-fold of AUC(0-t, kidney) and 13.96-fold of MRT(0-t, kidney) compared to TP. Additionally, TPAG presented improved protective effect against renal ischemia/reperfusion injury. Compared to TP's multiorgan toxicity, TPAG showed minimum toxicity toward the kidney and genital systems, and greatly lowered toxicity in the liver and immune systems. In sum, our study presented an alternative structure modification of triptolide with improved safety and efficacy profiles.

  18. Comparative effects of enalapril and nifedipine on renal hemodynamics in hypertensive renal allograft recipients.

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    Abu-Romeh, S H; el-Khatib, D; Rashid, A; Patel, M; Osman, N; Fayyad, M; Scheikhoni, A; Higazi, A S

    1992-04-01

    The comparative effects of enalapril (E) and nifedipine (N) on renal hemodynamics were assessed in twenty-two moderately hypertensive, cadaveric renal transplant patients who were maintaining stable renal function. Fourteen patients were on cyclosporin (CSA) and eight were receiving azathioprine with prednisolone (AZA). In each patient effective renal plasma flow (ERPF) was determined four times, first baseline, second with E, third as another baseline after a washout period, and fourth with N; and renal vascular resistance (RVR) was derived in each. ERPF and RVR were significantly compromised in the CSA group (202 +/- 55 ml/min and 65 +/- 18 mmHg/ml/min) compared to the AZA group (302 +/- 99 and 43 +/- 15 respectively). During E therapy, RVR further increased in the CSA group to 82 +/- 37 while it decreased in the AZA group to 31 +/- 7 (both changes were significant when compared to their respective baseline values). N, on the other hand, only significantly lowered RVR in the AZA group. Furthermore, two patients, one from each group, developed acute reversible renal failure shortly after E therapy. However, both agents were effective in lowering blood pressure to a comparable degree in both groups. In conclusion, our data showed a somewhat less favourable renal hemodynamic response to short-term enalapril therapy in hypertensive renal transplant patients maintained on CSA. However, the significance of such hemodynamic changes for long-term renal function remains uncertain.

  19. Renal impairment and late toxicity in germ-cell cancer survivors

    DEFF Research Database (Denmark)

    Lauritsen, J.; Mortensen, M. S.; Kier, M. G. G.

    2015-01-01

    Background Treatment with bleomycin–etoposide–cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large...... cohort of germ-cell cancer survivors. Patients and methods BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity. GFR were measured (51Cr-EDTA clearance) before and after treatment and at 1, 3 and 5-year follow......-up. The influence of BEP on GFR was evaluated with a linear mixed model. Risk factors for late toxicity were identified by a landmark analysis adjusting for covariates. The cohort was compared with the background population with standardized hospitalization/mortality rates. Results GFR changed (ΔGFR) −11.3%, −15...

  20. Renal Toxicity of Mercuric Chloride at Different Time Intervals in Rats

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    W.A. Al-Madani

    2009-01-01

    Full Text Available This study was undertaken to study the renal toxicity of mercuric chloride in rats at different periods of time. The following groups of rats were studied: i control, ii placebo, iii rats injected with a single ip dose of 100 mg/kg body weight of 2, 3 dimercapto- 1-propanesulfonic acid, iv rats injected with a single ip dose of 100 mg/kg body weight of 2, 3 dimercapto-1-propanesulfonic acid (DMPS followed by a single dose ip of 2.0 mg HgCl2/kg body weight one hour after DMPS injection v rats injected with a single ip dose of 2.0 mg HgCl2/kg body weight. Results indicate that mercuric chloride was more toxic after 48 hours of its administration when compared to 24 hours. Mercuric chloride administration caused an impairment of renal function which was evident from a significant decrease in urine volume, urinary excretion of urea, creatinine and glomerular filteration rate (P < 0.001 when compared to other treated groups. There was an increased excretion of protein, albumin and γ—glutamyltransferase in the urine of mercuric chloride treated rats. Administration of 2, 3 dimercapto-1-propanesulfonic acid before mercuric chloride treatment caused the altered indices to return to near normal levels.

  1. Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.

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    Emil Schüler

    Full Text Available The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity.C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys. At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a global transcriptional variations in kidney tissues, (b morphological changes in the kidneys, (c changes in white and red blood cell count as well as blood levels of urea, and (d changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy.In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months.Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm applicability of these

  2. Age-related differences in susceptibility to cisplatin-induced renal toxicity.

    Science.gov (United States)

    Espandiari, P; Rosenzweig, B; Zhang, J; Zhou, Y; Schnackenberg, L; Vaidya, V S; Goering, P L; Brown, R P; Bonventre, J V; Mahjoob, K; Holland, R D; Beger, R D; Thompson, K; Hanig, J; Sadrieh, N

    2010-03-01

    Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague-Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6 mg kg(-1) i.p.). Urine samples were collected prior and up to 72 h after treatment in animals that were >or= 25 days old. Several serum, urinary and 'omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 >or= 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers.

  3. Effects of Sodium Selenite on Formaldehyde Induced Renal Toxicity in Mice

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    Shabnam Mohammadi 1,2 * , Maryam Moghimian 3, Hanieh Torabzadeh 4, Mahla Langari 4, Roghayeh Nazeri 4, Zahra Karimi 4, Elham Sangari 4, Najmeh Jagarmi 5, Alireza Mohammad Zadeh 3, Mehdi Karimi 7, Kamyar Tavakkoli 8, Ali Delshad 9, Fatemeh Mohammadzadeh 3, Majid Ghayour-Mobarhan 10

    2016-12-01

    Full Text Available Background: Formaldehyde is widely used for industrial applications. Renal injury is an adverse effect associated with formaldehyde. Few studies have explored the potential benefits of protective factors on formaldehyde induced renal toxicity. This study evaluated the dose dependent effects of sodium selenite on the biochemical and histopathological effects of formaldehyde on murine kidney. Methods: Forty eight adult Balb/c male mice were randomized into six groups: a control group, a formaldehyde group and experimental III-VI groups. Formaldehyde group was injected with 10 mg/kg formaldehyde and groups III-VI received intraperitoneally doses of 0.1, 0.2, 0.4, 0.8 mg/kg selenium. After two weeks, a stereological study was done in accordance with the principle of Cavalieri and serum concentrations of urea and creatinine were measured. Data were analyzed using ANOVA and SPSS software. Results: Glomerosclerosis, necrosis and vacuolization were observed in the convoluted tubules of animals treated with formaldehyde. The biochemical markers, volume and count of glomeruli in the group treated with formaldehyde was significantly difference compared to the control group (P<0.05. The volume of the glomeruli in the group treated with 0.2 and 0.4 mg selenium and urea level in the group treated with 0.4 and 0.1 mg/kg selenium was significantly difference compared to the control group (P <0.05. The count of glomeruli and creatinine level in the selenium group was significantly difference compared to the control group (P ≤ 0.0001. Conclusions: A dose of 0.2 mg/kg of sodium selenite caused partial protective effect on the renal tissue and function in exposed to formaldehyde.

  4. Relationships between Serum Levels of Atazanavir and Renal Toxicity or Lithiasis

    OpenAIRE

    Marinescu, C. I.; Leyes, M.; M. A. Ribas; Peñaranda, M.; Murillas, J.; Campins, A. A.; Martin-Pena, L.; Barcelo, B.; Barceló-Campomar, C.; Grases, F.; Frontera, G; Melchor Riera Jaume

    2015-01-01

    The main aim of this study is to describe the relationship between serum levels of atazanavir, renal toxicity, and lithiasis. This is a prospective observational study of patients being treated with atazanavir (ATV) at Son Espases Teaching Hospital, Palma de Mallorca, between 2011 and 2013. The study includes 98 patients. Sixteen were found to have a history of urolithiasis. During a median monitoring period of 23 months, nine patients suffered renal colic, in three of whom ATV crystals were ...

  5. Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

    Science.gov (United States)

    Ko, J-L; Tsai, C-H; Liu, T-C; Lin, M-Y; Lin, H-L; Ou, C-C

    2016-08-01

    Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity. © The Author(s) 2015.

  6. Relationships between Serum Levels of Atazanavir and Renal Toxicity or Lithiasis

    Directory of Open Access Journals (Sweden)

    C. I. Marinescu

    2015-01-01

    Full Text Available The main aim of this study is to describe the relationship between serum levels of atazanavir, renal toxicity, and lithiasis. This is a prospective observational study of patients being treated with atazanavir (ATV at Son Espases Teaching Hospital, Palma de Mallorca, between 2011 and 2013. The study includes 98 patients. Sixteen were found to have a history of urolithiasis. During a median monitoring period of 23 months, nine patients suffered renal colic, in three of whom ATV crystals were evidenced in urine. Cumulative incidence of renal colic was 9.2 per 100 patients. The variables related to having renal colic were the presence of alkaline urine pH and lower basal creatinine clearance. The mean serum level of ATV was slightly higher in patients with renal colic—1,303 μg/L versus 1,161 μg/L—but did not reach statistical significance. Neither were any significant differences detected by analysing the levels according to the timetable for ATV dosage. Cumulative incidence of renal colic was high in patients being treated with ATV, in 33% of whom the presence of ATV crystals was evidenced in urine. We were unable to demonstrate a relationship between ATV serum levels and renal colic or progression towards renal failure.

  7. Relationships between Serum Levels of Atazanavir and Renal Toxicity or Lithiasis.

    Science.gov (United States)

    Marinescu, C I; Leyes, M; Ribas, M A; Peñaranda, M; Murillas, J; Campins, A A; Martin-Pena, L; Barcelo, B; Barceló-Campomar, C; Grases, F; Frontera, G; Riera Jaume, Melchor

    2015-01-01

    The main aim of this study is to describe the relationship between serum levels of atazanavir, renal toxicity, and lithiasis. This is a prospective observational study of patients being treated with atazanavir (ATV) at Son Espases Teaching Hospital, Palma de Mallorca, between 2011 and 2013. The study includes 98 patients. Sixteen were found to have a history of urolithiasis. During a median monitoring period of 23 months, nine patients suffered renal colic, in three of whom ATV crystals were evidenced in urine. Cumulative incidence of renal colic was 9.2 per 100 patients. The variables related to having renal colic were the presence of alkaline urine pH and lower basal creatinine clearance. The mean serum level of ATV was slightly higher in patients with renal colic-1,303 μg/L versus 1,161 μg/L-but did not reach statistical significance. Neither were any significant differences detected by analysing the levels according to the timetable for ATV dosage. Cumulative incidence of renal colic was high in patients being treated with ATV, in 33% of whom the presence of ATV crystals was evidenced in urine. We were unable to demonstrate a relationship between ATV serum levels and renal colic or progression towards renal failure.

  8. Renal artery stenosis: comparative assessment by unenhanced renal artery mra versus contrast-enhanced MRA

    Energy Technology Data Exchange (ETDEWEB)

    Khoo, Michael M.Y.; Deeab, Dhafer; Gedroyc, Wladyslaw M.W.; Dick, Elizabeth A. [St Mary' s Hospital, Imperial College NHS Trust, Department of MRI, London (United Kingdom); Duncan, Neil; Taube, David [Hammersmith Hospital, Imperial College NHS Trust, Department of Nephrology, London (United Kingdom)

    2011-07-15

    To evaluate steady-state free precession (SSFP) non-contrast-enhanced MR angiography (Unenhanced-MRA) versus conventional contrast-enhanced MR angiography (CE-MRA) in the detection of renal artery stenosis (RAS). Retrospective analysis of 70 consecutive patients referred for suspected RAS, examined by SSFP Unenhanced-MRA and CE-MRA. Image quality, quality of visible renal arterial segments, presence and grade of RAS were evaluated. The Unenhanced-MRA were compared against reference standard CE-MRA results. 149 renal arteries were assessed with 21 haemodynamically significant stenoses ({>=}50% stenosis) demonstrated by CE-MRA. Combined sensitivity and specificity for RAS detection by Unenhanced-MRA was 72.8% and 97.8% respectively. There is substantial correlation for RAS detection between Unenhanced-MRA and CE-MRA with kappa values of between 0.64 and 0.74. There was excellent inter-observer correlation for RAS on Unenhanced-MRA (kappa values 0.82-1.0). Our study has shown Unenhanced-MRA to be a viable alternative to CE-MRA, yielding images equal in quality without the requirement for gadolinium contrast agents. The sensitivity and specificity for the detection of haemodynamically significant stenoses are comparable to CE-MRA. Potentially, Unenhanced-MRA could be used as an initial investigation to avoid performing CE-MRA in patients with normal renal arteries, however we suggest that its real value will lie in being complementary to CE-MRA. (orig.)

  9. Investigation of cadmium toxicity on renal epithelial cells using nuclear microprobe analysis

    Energy Technology Data Exchange (ETDEWEB)

    Khodja, Hicham E-mail: khodja@drecam.cea.fr; Avoscan, Laure; Carriere, Marie; Carrot, Francine; Gouget, Barbara

    2003-09-01

    Cadmium is a highly toxic metal that causes well-known severe renal damages. Its toxicity is frequently investigated in vitro using numerous epithelial models. The accumulation and transport of cadmium in cultured renal epithelial cells has been studied by means of nuclear microscopy (micro-PIXE coupled with micro-RBS) for cell monolayer analyses, and by ICP-MS for culture medium analyses. Cell viability, measured by biochemical tests, was used as toxicity indicator. Dependence on cadmium concentration (1-100 {mu}M) and exposure time (1-24 h) was found. Micro-PIXE reveals a strong anti-correlation of intra-cellular cadmium concentration with zinc concentration, a biological metal, suggesting substitution mechanism of both metals.

  10. Calcineurin inhibitor toxicity in renal allografts: Morphologic clues from protocol biopsies

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    Sharma Alok

    2010-10-01

    Full Text Available Background: Calcineurin inhibitors (cyclosporine and tacrolimus are important constituents of post renal transplant immunosuppression. However, renal toxicity limits their utility. Histological features of calcineurin inhibitor toxicity (CNIT have been the subject of few studies using protocol biopsy samples, and consensus on diagnostic criteria is still evolving. Aims: To analyze the spectrum of histological changes in protocol renal allograft biopsies with evidence of CNIT and identify additional features that are likely to help the pathologist in arriving at a diagnosis. Materials and Methods: One hundred and forty protocol allograft biopsies performed at 1, 6 and 12 months post renal transplant were studied. The defining features of CNIT included: isometric vacuolization of proximal tubular cells, arteriolar hyalinosis with medial/peripheral nodules and striped pattern of tubular atrophy/interstitial fibrosis. Other features such as global glomerulosclerosis, vacuolization of smooth muscle cells of arterioles, tubular microcalcinosis, ischemic shrinkage of glomeruli and hyperplasia of juxtaglomerular apparatus (JGA were also analyzed and graded semiquantitatively. Results: CNIT was seen in 17/140 protocol biopsies (12.1%. In addition to the diagnostic criteria, arteriolar hyalinosis, smooth muscle cell vacuolization of arterioles and hyperplasia of JGA were found to be useful indicators of CNIT. Conclusions: There is a relatively high incidence of CNIT in protocol allograft biopsies. A critical analysis of renal biopsy in adequate number of serial step sections to identify these features is mandatory, as many of these features are subtle and are likely to be missed if not specifically sought.

  11. Melamine-induced renal toxicity is mediated by the gut microbiota.

    Science.gov (United States)

    Zheng, Xiaojiao; Zhao, Aihua; Xie, Guoxiang; Chi, Yi; Zhao, Linjing; Li, Houkai; Wang, Congrong; Bao, Yuqian; Jia, Weiping; Luther, Mike; Su, Mingming; Nicholson, Jeremy K; Jia, Wei

    2013-02-13

    Melamine poisoning has become widely publicized after a recent occurrence of renal injury in infants and children exposed to melamine-tainted milk in China. This renal damage is believed to result from kidney stones formed from melamine and uric acid or from melamine and its cocrystallizing chemical derivative, cyanuric acid. However, the composition of the stones and the mechanism by which the stones are formed in the renal tubules are unknown. We report that cyanuric acid can be produced in the gut by microbial transformation of melamine and serves as an integral component of the kidney stones responsible for melamine-induced renal toxicity in rats. Melamine-induced toxicity in rats was attenuated and melamine excretion increased after antibiotic suppression of gut microbial activity [corrected]. We further demonstrated that melamine is converted to cyanuric acid in vitro by bacteria cultured from normal rat feces; Klebsiella was subsequently identified in fecal samples by 16S ribosomal DNA sequencing. In culture, Klebsiella terrigena was shown to convert melamine to cyanuric acid directly. Rats colonized by K. terrigena showed exacerbated melamine-induced nephrotoxicity. Cyanuric acid was detected in the kidneys of rats administered melamine alone, and the concentration after Klebsiella colonization was increased. These findings suggest that the observed toxicity of melamine may be conditional on the exact composition and metabolic activities of the gut microbiota.

  12. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

    Directory of Open Access Journals (Sweden)

    Aicha Fassi Fihri

    2016-06-01

    Full Text Available Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily; group 2: received oral lead acetate (2 g/kg.b.wt/daily; group 3: treated with oral honey (1g /kg.b.wt/daily and oral lead (2 g/kg.b.wt/daily, and group 4: received oral honey (1 g/kg.b.wt/daily. Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Results: Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. Conclusion: It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects.

  13. Biochemical, liver and renal toxicities of Melissa officinals hydroalcoholic extract on balb/C mice

    Directory of Open Access Journals (Sweden)

    Namjoo Abdolrasool

    2013-04-01

    Full Text Available Introduction: Melissa officinalis is usually used as antispasmodic, antiaxiety and antibacterial agent. However, its toxicity has not been evaluated, yet. In this study biochemical, liver and renal toxicities of Melissa officinals hydroalcoholic extract were evaluated in balb/C mice. Methods: In an experimental study, 21 balb/C male mice were randomly designated to three equal groups. Group I was treated with normal saline and groups II and III were respectively treated with 0.450 and 1.350 g/kg, hydroalcoholic extract of Melissa officinals daily for two weeks, intraperitoneally. Then on 15th day of the experiment, blood samples were obtained from the heart. The blood was centrifuged and then the sera were evaluated for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea and creatinine, using autoanalyzer and commercial kits. The liver and kidney tissues were also hystopathologically evaluated. The data were analyzed by one-way ANOVA, Tukey’s post hoc test, and Kruskal-Wallis at a significance level of p<0.05. Results: Melissa officinals dose dependently caused a significant reduction in alkaline phosphatase and alanine aminotransferase levels compared to the control group. Furthermore, Melissa officinals extract had no effect on the amount of urea and creatinine compared to the control group. The liver and kidney histopathological changes in the groups that received different doses of the extract showed mild, moderate, and severe tissue injuries. Conclusion: The biochemical analysis in this study indicates that the extract of Melissa officinals causes liver tissue damage in mice; therefore, its consumption in high doses should be avoided.

  14. Protective effect of pomegranate flower extract against gentamicin-induced renal toxicity in male rats

    OpenAIRE

    Sadeghi, Ferdos; Nematbakhsh, Mehdi; Noori-Diziche, Ali; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir; Nasri, Hamid; Mansouri, Azam; Dehghani, Aghdas; Saberi, Shadan; Shirdavani, Soheila; Ashrafi, Farzaneh

    2015-01-01

    Introduction: Gentamicin (GM) as an antibiotic is used in clinic. However, its administration is limited by side effects such as nephrotoxicity. Herbal extracts could be used in therapeutic approaches. Objectives: The present study was planned to investigate whether pomegranate flower extract (PFE) could ameliorate GM-induced renal toxicity in male rats. Materials and Methods: Twenty eight male Wistar rats were divided into 5 groups. Groups 1 and 2 respectively received PFE 25 and 50 mg/kg fo...

  15. Protective effects of hesperidin on oxidative stress, dyslipidaemia and histological changes in iron-induced hepatic and renal toxicity in rats

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    Leelavinothan Pari

    2015-01-01

    Full Text Available The present study was to evaluate the protective role of hesperidin (HDN against iron-induced hepatic and renal toxicity in rats. Administration of iron (30 mg/kg body weight intraperitoneally for 10 days, the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers and iron concentration in blood were significantly (p < 0.05 increased. The toxic effect of iron was also indicated by significant (p < 0.05 decrease in the levels of plasma, liver and kidney of enzymatic and non-enzymatic antioxidants. Administration of hesperidin at different doses (20, 40 and 80 mg/kg body weight significantly (p < 0.05 reversed the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers, restored the levels of hepatic, renal enzymatic antioxidants and non-enzymatic antioxidants with decrease in iron concentration in blood. Hesperidin at a dose of 80 mg/kg body weight exhibits significant protection on hepatic and renal when compared with other two doses (20 and 40 mg/kg body weight. All these changes were corroborating by histological observations of liver and kidney. This study demonstrated the protective role of hesperidin in reducing toxic effects of iron in experimental rats.

  16. The use of biomarkers for assessing HAART-associated renal toxicity in HIV-infected patients.

    Science.gov (United States)

    del Palacio, María; Romero, Sara; Casado, Jose L

    2012-09-01

    Renal toxicity has become an important issue in HIV-infected patients receiving highly active antiretroviral therapy (HAART). Several biomarkers are available for monitoring renal function, although no consensus exists on how best to apply these tools in HIV infection. The best biomarker is the glomerular filtration rate (GFR), and several creatinine-based estimates equations of GFR are widely used in HIV infection, with clinical advantages for the equation developed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Although serum cystatin C has been proposed as a more sensitive marker of renal dysfunction in HIV infection, it may be affected by ongoing inflammation. Tubular dysfunction can be simple or complex, depending on whether the tubular transport of one or more substances is affected. Multiple renal tubular dysfunction or Fanconi syndrome is characterized by alterations in the reabsorption of glucose, amino acids, phosphate and often also bicarbonate. Therefore, Fanconi syndrome would be the tip of the iceberg, and the most unusual and severe manifestation. In the last years, several low molecular weight proteins as markers of tubular alteration, including retinol-binding protein, b2-microglobulin, and neutrophil gelatinase associated lipocalin have become available. Different studies have shown differences in urine concentrations of these proteins in patients receiving tenofovir, but again, no consistent data have shown their clinical usefulness in predicting the clinical consequences of tubular alteration. Thus, we review findings from recent studies performed in this area to describe the performance of new biomarkers for renal damage in HIV-infected patients.

  17. Comparative metal oxide nanoparticle toxicity using embryonic zebrafish

    Directory of Open Access Journals (Sweden)

    Leah C. Wehmas

    2015-01-01

    Full Text Available Engineered metal oxide nanoparticles (MO NPs are finding increasing utility in the medical field as anticancer agents. Before validation of in vivo anticancer efficacy can occur, a better understanding of whole-animal toxicity is required. We compared the toxicity of seven widely used semiconductor MO NPs made from zinc oxide (ZnO, titanium dioxide, cerium dioxide and tin dioxide prepared in pure water and in synthetic seawater using a five-day embryonic zebrafish assay. We hypothesized that the toxicity of these engineered MO NPs would depend on physicochemical properties. Significant agglomeration of MO NPs in aqueous solutions is common making it challenging to associate NP characteristics such as size and charge with toxicity. However, data from our agglomerated MO NPs suggests that the elemental composition and dissolution potential are major drivers of toxicity. Only ZnO caused significant adverse effects of all MO particles tested, and only when prepared in pure water (point estimate median lethal concentration = 3.5–9.1 mg/L. This toxicity was life stage dependent. The 24 h toxicity increased greatly (∼22.7 fold when zebrafish exposures started at the larval life stage compared to the 24 h toxicity following embryonic exposure. Investigation into whether dissolution could account for ZnO toxicity revealed high levels of zinc ion (40–89% of total sample were generated. Exposure to zinc ion equivalents revealed dissolved Zn2+ may be a major contributor to ZnO toxicity.

  18. p-Methoxyl-diphenyl diselenide protects against cisplatin-induced renal toxicity in mice.

    Science.gov (United States)

    Wilhelm, Ethel A; Bortolatto, Cristiani F; Nogueira, Cristina W

    2012-05-01

    The present study was designed to investigate the effects of p-methoxyl-diphenyl diselenide (OMePhSe)(2) on oxidative stress and renal damage parameters of mice exposed to cisplatin. (OMePhSe)(2) (50 and 100 mg/kg/day) was orally administered to mice for six consecutive days. On the third day after the beginning of (OMePhSe)(2) treatment, the renal toxicity was induced by injecting cisplatin (10 mg/kg intraperitoneal) in mice. (OMePhSe)(2) treatment (50 mg/kg) partially reduced plasma urea and creatinine levels increased by cisplatin. Histopathological examination of kidneys showed that (OMePhSe)(2) ameliorated renal injury caused by cisplatin. (OMePhSe)(2) attenuated the decrease in reduced glutathione (GSH) and ascorbic acid (AA) levels, the inhibition of glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and catalase (CAT) activities caused by cisplatin in kidney. (OMePhSe)(2) treatment partially protected against the inhibition of renal δ-aminolevulinic dehydratase (δ-ALA-D) activity caused by cisplatin. No alteration in renal lipid peroxidation levels was found in cisplatin and/or (OMePhSe)(2) groups. (OMePhSe)(2) was effective against the increase in reactive species (RS) levels caused by the cisplatin exposure. Based on the renoprotective and antioxidant actions of (OMePhSe)(2) we suggest that this organoselenium compound could be considered a feasible candidate to protect against toxicity commonly encountered in cisplatin exposure.

  19. The molecular clock: a focus on chronopharmacological strategies for a possible control of aminoglycoside renal toxicity

    Directory of Open Access Journals (Sweden)

    Rebuelto M

    2012-01-01

    Full Text Available Marcela RebueltoFarmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, ArgentinaAbstract: Chronotherapy applies biological rhythmicity in order to optimize clinical treatments, relating the dosing time of the drugs to the daily variations of their therapeutic and unwanted side effects due to the fluctuations in physiological processes involved in their pharmacokinetics and/or pharmacodynamics. The goal of chronotherapy is to administer treatments at the time of day that enhances both their effectiveness and tolerance. This review intends to (1 provide the theoretical rationale behind the use of aminoglycosides during extended interval schedule chronotherapy in clinical practice and (2 target the underlying molecular mechanisms of renal toxicity, the main unwanted side effect. Previous reports suggest that aminoglycoside therapy may benefit from a chronopharmacological approach. Temporal variations in the renal blood flow and glomerular filtration rate and several clock-dependent molecular mechanisms contributing to the daily changes in electrolyte and water urinary excretion have been reported. Daily differences in aminoglycoside toxicity and kinetic disposition have been found in laboratory animals and human patients. Nephrotoxicity and renal cortical accumulation are higher when drugs are administered during the rest phase than during the active phase. Active translocation of aminoglycosides into renal cells is mediated by the megalin/cubilin receptor complex located at the luminal epithelial cell membrane. The complex regulation of this endocytic mechanism deserves further study, in order to dilucidate the molecular bases that may be involved in chronotherapeutic strategies developed for minimizing aminoglycoside accumulation in the renal cells, and thus, increasing their tolerance.Keywords: biological rhythms, chronopharmacology, chronotherapeutics, aminoglycosides

  20. Comparative Toxicity of Gasoline and Diesel Engine Emissions

    Energy Technology Data Exchange (ETDEWEB)

    JeanClare Seagrave; Joe L. Mauderly; Barbara Zielinska; John Sagebiel; Kevin Whitney; Doughlas R. Lawson; Michael Gurevich

    2000-06-19

    Better information on the comparative toxicity of airborne emissions from different types of engines is needed to guide the development of heavy vehicle engine, fuel, lubricant, and exhaust after-treatment technologies, and to place the health hazards of current heavy vehicle emissions in their proper perspective. To help fill this information gap, samples of vehicle exhaust particles and semi-volatile organic compounds (SVOC) were collected and analyzed. The biological activity of the combined particle-SVOC samples is being tested using standardized toxicity assays. This report provides an update on the design of experiments to test the relative toxicity of engine emissions from various sources.

  1. Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs.

    Science.gov (United States)

    Dobson, Roy L M; Motlagh, Safa; Quijano, Mike; Cambron, R Thomas; Baker, Timothy R; Pullen, Aletha M; Regg, Brian T; Bigalow-Kern, Adrienne S; Vennard, Thomas; Fix, Andrew; Reimschuessel, Renate; Overmann, Gary; Shan, Yuching; Daston, George P

    2008-11-01

    This paper describes research relating to the major recall of pet food that occurred in Spring 2007 in North America. Clinical observations of acute renal failure in cats and dogs were associated with consumption of wet pet food produced by a contract manufacturer producing for a large number of companies. The affected lots of food had been formulated with wheat gluten originating from China. Pet food and gluten were analyzed for contaminants using several configurations of high-performance liquid chromatography (HPLC) and mass spectrometry (MS), which revealed a number of simple triazine compounds, principally melamine and cyanuric acid, with lower concentrations of ammeline, ammelide, ureidomelamine, and N-methylmelamine. Melamine and cyanuric acid, have been tested and do not produce acute renal toxicity. Some of the triazines have poor solubility, as does the compound melamine cyanurate. Pathological evaluation of cats and dogs that had died from the acute renal failure indicated the presence of crystals in kidney tubules. We hypothesized that these crystals were composed of the poorly soluble triazines, a melamine-cyanuric acid complex, or a combination. Sprague dawley rats were given up to 100 mg/kg ammeline or ammelide alone, a mixture of melamine and cyanuric acid (400/400 mg/kg/day), or a mixture of all four compounds (400 mg/kg/day melamine, 40 mg/kg/day of the others). Neither ammeline nor ammelide alone produced any renal effects, but the mixtures produced significant renal damage and crystals in nephrons. HPLC-MS/MS confirmed the presence of melamine and cyanuric acid in the kidney. Infrared microspectroscopy on individual crystals from rat or cat (donated material from a veterinary clinic) kidneys confirmed that they were melamine-cyanuric acid cocrystals. Crystals from contaminated gluten produced comparable spectra. These results establish the causal link between the contaminated gluten and the adverse effects and provide a mechanistic explanation

  2. Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity.

    Science.gov (United States)

    Moghadasali, Reza; Mutsaers, Henricus A M; Azarnia, Mahnaz; Aghdami, Nasser; Baharvand, Hossein; Torensma, Ruurd; Wilmer, Martijn J G; Masereeuw, Rosalinde

    2013-07-01

    Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity to regenerate renal tubule epithelia and repair renal function without fusing with resident tubular cells. The goal of the present project was to investigate the role of MSCs secreted cytokines on tubule cell viability and regeneration after a toxic insult, using a conditionally immortalized human proximal tubule epithelial cell (ciPTEC) line. Gentamicin was used to induce nephrotoxicity, and cell viability and migration were studied in absence and presence of human MSC-conditioned medium (hMSC-CM) i.e. medium containing soluble factors produced and secreted by MSCs. Exposure of ciPTEC to 0-3000 μg/ml gentamicin for 24 h caused a significant dose-dependent increase in cell death. We further demonstrated that the nephrotoxic effect of 2000 μg/ml gentamicin was recovered partially by exposing cells to hMSC-CM. Moreover, exposure of ciPTEC to gentamicin (1500-3000 μg/ml) for 7 days completely attenuated the migratory capacity of the cells. In addition, following scrape-wounding, cell migration of both untreated and gentamicin-exposed cells was increased in the presence of hMSC-CM, as compared to exposures to normal medium, indicating improved cell recovery. Our data suggest that cytokines secreted by MSCs stimulate renal tubule cell regeneration after nephrotoxicity. Copyright © 2012 Elsevier GmbH. All rights reserved.

  3. Prevalence of renal and hepatobiliary disease, laboratory abnormalities, and potentially toxic medication exposures among persons with COPD

    Directory of Open Access Journals (Sweden)

    Mapel DW

    2013-03-01

    Full Text Available Douglas W Mapel,1 Jenõ P Marton21Lovelace Clinic Foundation, Albuquerque, New Mexico, NM, USA; 2Health Economics and Outcomes Research, Pfizer Inc, New York, NY, USABackground: The purpose of this study was to describe the prevalence of renal and hepatic disease, related laboratory abnormalities, and potentially hepatotoxic and nephrotoxic medication use in a population-based cohort of persons with chronic obstructive pulmonary disease (COPD.Methods: This was a retrospective case-control cohort analysis of COPD patients enrolled in one regional health system for at least 12 months during a 36-month study period (n = 2284. Each COPD patient was matched by age and gender to up to three persons not diagnosed with COPD (n = 5959.Results: The mean age for cases and controls was 70.3 years, and 52.5% were women. The COPD cohort had significantly higher prevalences (cases/100 of acute, chronic, and unspecified renal failure as compared with controls (1.40 versus 0.59, 2.89 versus 0.79, and 1.09 versus 0.44, respectively. Among the cases, 31.3% had at least one renal or urinary tract diagnosis during the study period, as compared with 21.1% of controls. COPD cases also had more gallbladder disease (2.76 versus 1.63 and pancreatic disease (1.40 versus 0.60, but not hepatic disease. COPD patients were more likely to have at least one serum creatinine level (5.1 versus 2.1 or liver aspartate aminotransferase level (4.5 versus 2.7 that was more than twice the upper limit of normal. COPD patients had prescription fills for an average of 17.6 potentially nephrotoxic and 27.4 hepatotoxic drugs during the study period, as compared with 13.6 and 19.9 for the controls (P value for all comparisons < 0.01.Conclusion: COPD patients have a substantially increased prevalence of renal, gallbladder, and pancreatic diseases, as well as abnormal renal and hepatic laboratory values, but not diagnosed liver disease. COPD patients are also more likely to be prescribed

  4. Phytopreventative effects of Gynostemma pentaphyllum against acute Indomethacin-induced gastrointestinal and renal toxicity in rats.

    Science.gov (United States)

    Hesse, Cristina; Razmovski-Naumovski, Valentina; Duke, Colin C; Davies, Neal M; Roufogalis, Basil D

    2007-06-01

    In the present study, the phytoprotective effects of gypenosides from Gynostemma pentaphyllum throughout the gastrointestinal tract and kidney were examined in indomethacin-treated rats. Indomethacin induced gastric and intestinal damage as well as renal toxicity after a single toxicological dose (10 mg/kg) in rats. Acute oral administration of the gypenoside extract (200 mg/kg) significantly reduced gastric and intestinal toxicity induced by indomethacin as measured by ulceration, caecal haemoglobin and plasma haptoglobin. A significant decrease in small intestinal lactose fermenting enterobacteria was evident in animals treated with indomethacin and those pre-treated with G. pentaphyllum then indomethacin. In the renal system, kidney toxicity was evident after indomethacin and in animals pre-treated with indomethacin plus G. pentaphyllum with an increase in urinary N-acetyl-beta-glucosaminidase and a decrease in urinary sodium and chloride electrolyte output. However, a significant increase in urinary microprotein in indomethacin-treated animals was not present in indomethacin plus G. pentaphyllum-treated animals. These studies demonstrate the efficacy of Gynostemma pentaphyllum in lowering gastrointestinal damage induced by indomethacin. The results suggest further investigations of Gynostemma gypenosides are warranted to examine the mechanisms of this phytoprotective activity. (c) 2007 John Wiley & Sons, Ltd.

  5. The Protective Roles of Zinc and Magnesium in Cadmium-Induced Renal Toxicity in Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Nasim Babaknejad

    2014-12-01

    Full Text Available Background: Cadmium (Cd is a heavy metal that has widespread use. It enters the food chain in different ways, including soil and water. Cadmium can cause dysfunction of different body organs. Zinc (Zn and magnesium (Mg supplementation can have protective effects against cadmium toxicity due to their antagonistic and antioxidants properties. This study examines the influence of supplemental Zn and Mg on Cd renal toxicity. Methods: Young male Wistar rats were divided into six groups of five. The Cd group received 1 mg Cd/kg and the control group received 0.5 mg/kg normal saline (i.p.. The other four groups were administered 1 mg/kg Cd+0.5 mg/kg Zn, 1 mg/kg Cd+1.5 mg/kg Zn, 1 mg/kg Cd+ 0.5 mg/kg Mg, and 1 mg/kg Cd+ 1.5 mg/kg Mg (i.p. for 21 days. Then, serum sodium, potassium, urea, creatinine, and protein levels were measured. Results: The results indicated that creatinine and protein levels decreased while urea, sodium, and potassium levels increased as a result of Cd exposure. Co-administered Cd and Zn and Mg decreased urea and increased sodium serum level in comparison to the cadmium group. Treatment by Mg, contrary to co-administered Cd and Zn, reduced serum protein level compared to the cadmium group. Compared to the cadmium treated group, Zn and Mg treatment enhanced serum creatinine level and reduced serum potassium level. Conclusion: The findings seem to suggest that zinc and magnesium compounds, due to their antagonistic and antioxidant activities, can protect Cd renal toxic effects in a dose-dependent manner.

  6. Efficacy and Toxicity of Mammalian Target Rapamycin Inhibitors in Patients with Metastatic Renal Cell Carcinoma with Renal Insufficiency: The Korean Cancer Study Group GU 14-08

    Science.gov (United States)

    Kim, Ki Hyang; Kim, Joo Hoon; Lee, Ji Young; Kim, Hyo Song; Heo, Su Jin; Kim, Ji Hyung; Kim, Ho Young; Rha, Sun Young

    2016-01-01

    Purpose We evaluated the efficacy and toxicity of mammalian target rapamycin inhibitors in Korean patients with metastatic renal cell carcinoma (mRCC) with chronic renal insufficiency not requiring dialysis. Materials and Methods Korean patients with mRCC and chronic renal insufficiency not requiring dialysis treated with everolimus or temsirolimus between January 2008 and December 2014 were included. Patient characteristics, clinical outcomes, and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) durations were evaluated according to the degree of renal impairment. Results Eighteen patients were considered eligible for the study (median age, 59 years). The median glomerular filtration rate was 51.5 mL/min/1.73 m2. The best response was partial response in six patients and stable disease in 11 patients. The median PFS and OS durations were 8 months (95% confidence interval [CI], 0 to 20.4) and 32 months (95% CI, 27.5 to 36.5), respectively. The most common non-hematologic and grade 3/4 adverse events included stomatitis, fatigue, flu-like symptoms, and anorexia as well as elevated creatinine level. Conclusion Mammalian target rapamycin inhibitors were efficacious and did not increase toxicity in Korean patients with mRCC and chronic renal insufficiency not requiring dialysis. PMID:26875195

  7. Cystic Renal Oncocytoma and Tubulocystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Comparative Study.

    Science.gov (United States)

    Skenderi, Faruk; Ulamec, Monika; Vranic, Semir; Bilalovic, Nurija; Peckova, Kvetoslava; Rotterova, Pavla; Kokoskova, Bohuslava; Trpkov, Kiril; Vesela, Pavla; Hora, Milan; Kalusova, Kristyna; Sperga, Maris; Perez Montiel, Delia; Alvarado Cabrero, Isabel; Bulimbasic, Stela; Branzovsky, Jindrich; Michal, Michal; Hes, Ondrej

    2016-02-01

    Renal oncocytoma (RO) may present with a tubulocystic growth in 3% to 7% of cases, and in such cases its morphology may significantly overlap with tubulocystic renal cell carcinoma (TCRCC). We compared the morphologic and immunohistochemical characteristics of these tumors, aiming to clarify the differential diagnostic criteria, which facilitate the discrimination of RO from TCRCC. Twenty-four cystic ROs and 15 TCRCCs were selected and analyzed for: architectural growth patterns, stromal features, cytomorphology, ISUP nucleolar grade, necrosis, and mitotic activity. Immunohistochemical panel included various cytokeratins (AE1-AE3, OSCAR, CAM5.2, CK7), vimentin, CD10, CD117, AMACR, CA-IX, antimitochondrial antigen (MIA), EMA, and Ki-67. The presence of at least focal solid growth and islands of tumor cells interspersed with loose stroma, lower ISUP nucleolar grade, absence of necrosis, and absence of mitotic figures were strongly suggestive of a cystic RO. In contrast, the absence of solid and island growth patterns and presence of more compact, fibrous stroma, accompanied by higher ISUP nucleolar grade, focal necrosis, and mitotic figures were all associated with TCRCC. TCRCC marked more frequently for vimentin, CD10, AMACR, and CK7 and had a higher proliferative index by Ki-67 (>15%). CD117 was negative in 14/15 cases. One case was weakly CD117 reactive with cytoplasmic positivity. All cystic RO cases were strongly positive for CD117. The remaining markers (AE1-AE3, CAM5.2, OSCAR, CA-IX, MIA, EMA) were of limited utility. Presence of tumor cell islands and solid growth areas and the type of stroma may be major morphologic criteria in differentiating cystic RO from TCRCC. In difficult cases, or when a limited tissue precludes full morphologic assessment, immunohistochemical pattern of vimentin, CD10, CD117, AMACR, CK7, and Ki-67 could help in establishing the correct diagnosis.

  8. Non invasive assessment of renal artery using dual MRA techniques compared with invasive renal angiography in cases of renovascular hypertension

    Directory of Open Access Journals (Sweden)

    Y. Ragab

    2011-03-01

    Conclusion: The combined approach of non-invasive CE MRA and PC MRA techniques achieves a very high specificity, PPV and NPV for the detection of renal arterial pathomorphologic features as compared to standard renal angiography. Adding PC MRA to CE MRA helps to differentiate between mild and moderate stenoses as well as moderate and sever arterial stenotic lesions. So, CE MRA is a morphological test while PC MRA helps in grading the arterial stenoses.

  9. Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities.

    Science.gov (United States)

    Kollmannsberger, Christian; Bjarnason, Georg; Burnett, Patrick; Creel, Patricia; Davis, Mellar; Dawson, Nancy; Feldman, Darren; George, Suzanne; Hershman, Jerome; Lechner, Thomas; Potter, Amy; Raymond, Eric; Treister, Nathaniel; Wood, Laura; Wu, Shenhong; Bukowski, Ronald

    2011-01-01

    The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good- and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib. Drug dosing and treatment duration are correlated with response to treatment and survival. Treatment recommendations for hypertension have been published but, currently, no standard guidelines exist for the management of noncardiovascular side effects. To discuss the optimal management of noncardiovascular side effects, an international, interdisciplinary panel of experts gathered in November 2009. Existing literature on incidence, severity, and underlying mechanisms of side effects as well as on potential treatment options were carefully reviewed and discussed. On the basis of these proceedings and the thorough review of the existing literature, recommendations were made for the monitoring, prevention, and treatment of the most common noncardiovascular side effects and are summarized in this review. The proactive assessment and consistent and timely management of sunitinib-related side effects are critical to ensure optimal treatment benefit by allowing appropriate drug dosing and prolonged treatment periods.

  10. Amla as an antihyperglycemic and hepato-renal protective agent in fluoride induced toxicity

    Directory of Open Access Journals (Sweden)

    Rupal A Vasant

    2012-01-01

    Full Text Available Purpose of the study was to examine the antihyperglycemic and hepato-renal protective effects of Emblica officinalis (Eo fruit as a food supplement in fluoride induced toxicity. Eo fruit powder was incorporated into the diet (2.5, 5 and 10 gm % of fluoride exposed animals for a duration of 30 days. Fluoride exposure caused significant elevation in plasma glucose, serum glutamate oxaloacetate transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, acid phosphatase (ACP, alkaline phosphatase (ALP activities, hepatic glucose-6-phosphatase (G-6-Pase and decreased hepatic glycogen content, hexokinase activity and antioxidant profiles (hepatic and renal. An inclusion of Eo fruit powder significantly reduced plasma glucose levels, SGOT, SGPT, ACP and ALP activities, hepatic G-6-Pase activity and increased hepatic glycogen content and hexokinase activity. Hepatic and renal antioxidant status of fluoride exposed animals improved upon feeding Eo fruit powder. We, therefore, conclude that E. officinalis fruit could be useful in regulating hyperglycemia and enhances antioxidant status of fluoride exposed animals.

  11. Ocular toxicity of benzalkonium chloride homologs compared with their mixtures.

    Science.gov (United States)

    Okahara, Akihiko; Tanioka, Hidetoshi; Takada, Koichi; Kawazu, Kouichi

    2013-12-01

    This study was performed to assess the in vivo ocular toxicity of benzalkonium chloride (BAK) homologs compared with commercially available BAK (BAK mixture) and to assess the ocular toxicity of BAK homolog after repeated ocular application. Rabbit eyes were examined by ophthalmology and scanning electron microscopy (SEM) after 10 applications of BAK homologs with C12 (C12-BAK) and C14 (C14-BAK) alkyl chain lengths and a BAK mixture at concentrations of 0.001% (w/v), 0.003% (w/v), 0.005% (w/v), 0.01% (w/v) and 0.03% (w/v). The ocular toxicity of C12-BAK to rabbit eyes was examined by ophthalmology and histopathology after repeated ocular application for 39 weeks. In addition, the antimicrobial activities of C12-BAK and C14-BAK against A. niger, S. aureus and P. aeruginosa were assessed. Ocular toxicity of C12-BAK was less than those of the BAK mixture and C14-BAK. No ocular toxicity was noted after ocular application of 0.01% C12-BAK to rabbits for 39 weeks. C12-BAK showed antimicrobial activities at a concentration of 0.003%. These results suggest that the use of C12-BAK to replace BAK mixture as a preservative in ophthalmic solutions should be considered in order to reduce the incidence of the corneal epithelial cell injury induced clinically by BAK.

  12. Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds.

    Science.gov (United States)

    Behl, Mamta; Stout, Matthew D; Herbert, Ronald A; Dill, Jeffrey A; Baker, Gregory L; Hayden, Barry K; Roycroft, Joseph H; Bucher, John R; Hooth, Michelle J

    2015-07-03

    Occupational exposure to cobalt is of widespread concern due to its use in a variety of industrial processes and the occurrence of occupational disease. Due to the lack of toxicity and carcinogenicity data following exposure to cobalt, and questions regarding bioavailability following exposure to different forms of cobalt, the NTP conducted two chronic inhalation exposure studies in rats and mice, one on soluble cobalt sulfate heptahydrate, and a more recent study on insoluble cobalt metal. Herein, we compare and contrast the toxicity profiles following whole-body inhalation exposures to these two forms of cobalt. In general, both forms were genotoxic in the Salmonella T98 strain in the absence of effects on micronuclei. The major sites of toxicity and carcinogenicity in both chronic inhalation studies were the respiratory tract in rats and mice, and the adrenal gland in rats. In addition, there were distinct sites of toxicity and carcinogenicity noted following exposure to cobalt metal. In rats, carcinogenicity was observed in the blood, and pancreas, and toxicity was observed in the testes of rats and mice. Taken together, these findings suggest that both forms of cobalt, soluble and insoluble, appear to be multi-site rodent carcinogens following inhalation exposure. Published by Elsevier Ireland Ltd.

  13. Long-term renal toxicity in children following fractionated total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT)

    Energy Technology Data Exchange (ETDEWEB)

    Gerstein, Johanna; Meyer, Andreas; Fruehauf, Joerg; Karstens, Johann H.; Bremer, Michael [Dept. of Radiation Oncology, Medical School Hannover (Germany); Sykora, Karl-Walter [Dept. of Pediatric Hematology and Oncology, Medical School Hannover (Germany)

    2009-11-15

    Purpose: to retrospectively assess the incidence and time course of renal dysfunction in children ({<=} 16 years) following total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT). Patients and methods: between 1986 and 2003, 92 children (median age, 11 years; range, 3-16 years) underwent TBI before allogeneic SCT. 43 of them had a minimum follow-up of 12 months (median, 51 months; range, 12-186 months) and were included into this analysis. Conditioning regimen included chemotherapy and fractionated TBI with 12 Gy (n = 26) or 11.1 Gy (n = 17). In one patient, renal dose was limited to 10 Gy by customized renal shielding due to known nephropathy prior to SCt. Renal dysfunction was defined as an increase of serum creatinine > 1.25 times the upper limit of age-dependent normal. Results: twelve children (28%) experienced an episode of renal dysfunction after a median of 2 months (range, 1-10 months) following SCT. In all but one patient renal dysfunction was transient and resolved after a median of 8 months (range, 3-16 months). One single patient developed persistent renal dysfunction with onset at 10 months after SCT. None of these patients required dialysis. The actuarial 3-year freedom from persistent renal toxicity for children surviving > 12 months after SCt was 97.3%. Conclusion: the incidence of persistent renal dysfunction after fractionated TBI with total doses {<=} 12 Gy was very low in this analysis. (orig.)

  14. Renal function affects absorbed dose to the kidneys and haematological toxicity during {sup 177}Lu-DOTATATE treatment

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Johanna; Berg, Gertrud [Sahlgrenska University Hospital, Department of Oncology, Goeteborg (Sweden); Waengberg, Bo [Sahlgrenska University Hospital, Department of Surgery, Goeteborg (Sweden); Larsson, Maria [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Forssell-Aronsson, Eva; Bernhardt, Peter [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Medical Bioengineering, Goeteborg (Sweden)

    2015-05-01

    Peptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment. The study included 51 patients with an advanced neuroendocrine tumour who received {sup 177}Lu-DOTATATE treatment during 2006 - 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 - 8.2 GBq) was given at intervals of 6 - 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated. A significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p < 0.01). Patients with inferior renal function also experienced a higher grade of haematological toxicity during treatment (p = 0.01). The residence time of {sup 177}Lu in the whole body (range 0.89 - 3.0 days) was correlated with grade of haematological toxicity (p = 0.04) but not with renal absorbed dose (p = 0.53). Patients with inferior renal function were exposed to higher renal absorbed dose per administered activity and developed a higher grade of haematological toxicity during {sup 177}Lu-DOTATATE treatment. The study confirms the

  15. Drug-induced renal injury

    African Journals Online (AJOL)

    Drugs can cause acute renal failure by causing pre-renal, intrinsic or post-renal toxicity. Pre-renal ... incidence of drug dose adjustment in renal impairment in the SAMJ. ... Fever, haemolytic anaemia, thrombocytopenia, renal impairment and.

  16. Comparative Ochratoxin Toxicity: A Review of the Available Data.

    Science.gov (United States)

    Heussner, Alexandra H; Bingle, Lewis E H

    2015-10-22

    Ochratoxins are a group of mycotoxins produced by a variety of moulds. Ochratoxin A (OTA), the most prominent member of this toxin family, was first described by van der Merwe et al. in Nature in 1965. Dietary exposure to OTA represents a serious health issue and has been associated with several human and animal diseases including poultry ochratoxicosis, porcine nephropathy, human endemic nephropathies and urinary tract tumours in humans. More than 30 years ago, OTA was shown to be carcinogenic in rodents and since then extensive research has been performed in order to investigate its mode of action, however, this is still under debate. OTA is regarded as the most toxic family member, however, other ochratoxins or their metabolites and, in particular, ochratoxin mixtures or combinations with other mycotoxins may represent serious threats to human and animal health. This review summarises and evaluates current knowledge about the differential and comparative toxicity of the ochratoxin group.

  17. Comparative Ochratoxin Toxicity: A Review of the Available Data

    Directory of Open Access Journals (Sweden)

    Alexandra H. Heussner

    2015-10-01

    Full Text Available Ochratoxins are a group of mycotoxins produced by a variety of moulds. Ochratoxin A (OTA, the most prominent member of this toxin family, was first described by van der Merwe et al. in Nature in 1965. Dietary exposure to OTA represents a serious health issue and has been associated with several human and animal diseases including poultry ochratoxicosis, porcine nephropathy, human endemic nephropathies and urinary tract tumours in humans. More than 30 years ago, OTA was shown to be carcinogenic in rodents and since then extensive research has been performed in order to investigate its mode of action, however, this is still under debate. OTA is regarded as the most toxic family member, however, other ochratoxins or their metabolites and, in particular, ochratoxin mixtures or combinations with other mycotoxins may represent serious threats to human and animal health. This review summarises and evaluates current knowledge about the differential and comparative toxicity of the ochratoxin group.

  18. A case of sodium chlorite toxicity managed with concurrent renal replacement therapy and red cell exchange.

    Science.gov (United States)

    Romanovsky, Adam; Djogovic, Dennis; Chin, Dat

    2013-03-01

    Sodium chlorite is a powerful oxidizing agent with multiple commercial applications. We report the presentation and management of a single case of human toxicity of sodium chlorite. A 65-year-old man presented to hospital after accidentally ingesting a small amount of a sodium chlorite solution. His principal manifestations were mild methemoglobinemia, severe oxidative hemolysis, disseminated intravascular coagulation, and anuric acute kidney injury. He was managed with intermittent hemodialysis, followed by continuous venovenous hemofiltration for management of acute kidney injury and in an effort to remove free plasma chlorite. Concurrently, he underwent two red cell exchanges, as well as a plasma exchange, to reduce the burden of red cells affected by chlorite. These interventions resulted in the cessation of hemolysis with stabilization of serum hemoglobin and platelets. The patient survived and subsequently recovered normal renal function. This is only the second case of sodium chlorite intoxication reported in the medical literature and the first to report the use of renal replacement therapy in combination with red cell exchange in its management.

  19. An integrative view of cisplatin-induced renal and cardiac toxicities : Molecular mechanisms, current treatment challenges and potential protective measures

    NARCIS (Netherlands)

    Dugbartey, George J; Peppone, Luke J; de Graaf, Inge A M

    2016-01-01

    Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies

  20. Oral Manifestations of Chronic Kidney Disease and Renal Secondary Hyperparathyroidism: A Comparative Review.

    Science.gov (United States)

    Davis, Eric M

    2015-01-01

    Recent epidemiological studies have demonstrated that significant associations exist between oral disease and diseases involving non-oral tissues. Occasionally, the roles may be reversed and the oral cavity can be severely affected by systemic disease originating in another part of the body. Renal secondary hyperparathyroidism is a common endocrinopathy that occurs as a consequence of chronic azotemic kidney disease. Renal osteodystrophy, the most dramatic clinical consequence of renal secondary hyperparathyroidism is uncommon, but can result in demineralization of maxillofacial bones, loosening of teeth, and pathological jaw fractures. The purpose of this report is to update the current understanding of the pathophysiology of this endocrine disease and to compare the oral manifestations of renal secondary hyperparathyroidism in humans and companion animals. A 50-year review of the veterinary literature was undertaken to examine the clinical presentation of renal osteodystrophy in dogs, and to determine what clinical consequences of renal secondary hyperparathyroidism have been reported in domestic cats.

  1. Investigation of ifosfamide and chloroacetaldehyde renal toxicity through integration of in vitro liver-kidney microfluidic data and pharmacokinetic-system biology models.

    Science.gov (United States)

    Leclerc, Eric; Hamon, Jeremy; Bois, Frederic Yves

    2016-02-01

    We have integrated in vitro and in silico data to describe the toxicity of chloroacetaldehyde (CAA) on renal cells via its production from the metabolism of ifosfamide (IFO) by hepatic cells. A pharmacokinetic (PK) model described the production of CAA by the hepatocytes and its transport to the renal cells. A system biology model was coupled to the PK model to describe the production of reactive oxygen species (ROS) induced by CAA in the renal cells. In response to the ROS production, the metabolism of glutathione (GSH) and its depletion were modeled by the action of an NFE2L2 gene-dependent pathway. The model parameters were estimated in a Bayesian context via Markov Chain Monte Carlo (MCMC) simulations based on microfluidic experiments and literature in vitro data. Hepatic IFO and CAA in vitro intrinsic clearances were estimated to be 1.85 x 10(-9) μL s(-1) cell(-1) and 0.185 x 10(-9) μL s(-1) cell(-1) ,respectively (corresponding to an in vivo intrinsic IFO clearance estimate of 1.23 l h(-1) , to be compared to IFO published values ranging from 3 to 10 l h(-1) ). After model calibration, simulations made at therapeutic doses of IFO showed CAA renal intracellular concentrations ranging from 11 to 131 μM. Intracellular CAA concentrations above 70 μM induced intense ROS production and GSH depletion. Those responses were time and dose dependent, showing transient and non-linear kinetics. Those results are in agreement with literature data reporting that intracellular CAA toxic concentrations range from 35 to 320 μM, after therapeutic ifosfamide dosing. The results were also consistent with in vitro CAA renal cytotoxicity data.

  2. Tephrosia purpurea ameliorates N-diethylnitrosamine and potassium bromate-mediated renal oxidative stress and toxicity in Wistar rats.

    Science.gov (United States)

    Khan, N; Sharma, S; Alam, A; Saleem, M; Sultana, S

    2001-06-01

    In an earlier communication, we have shown that Tephrosia purpurea ameliorates benzoyl peroxide-induced oxidative stress in murine skin (Saleem et al. 1999). The present study was designed to investigate a chemopreventive efficacy of T purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N-diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine-initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate-induced lipid peroxidation and xanthine oxidase activities were significantly reduced (Ppurpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine and KBrO3.

  3. COMPARATIVE STUDY FOR SUBCHRONIC TOXICITY OF VASELINE OIL AND GLYCELAX

    Directory of Open Access Journals (Sweden)

    A. V. Voronkov

    2016-01-01

    Full Text Available Contemporary therapeutic approaches offer a wide range of laxative agents, which are often used without a control, exceeding the regime recommended. Therefore, the comparative study for subchronic toxicity of both drugs from this group (Vaseline oil and Glycelax appears interesting.The aim of the study was the comparison of a toxic influence of 14-days application of the drugs under study.Methods. The drugs were studied in two doses: higher therapeutic, and toxic, which 10 times exceeds therapeutic dose. We used “Polispektr-8/B” electrocardiograph, BC 2800vet (Mindray hematologic veterinary analyzer, BS-380 (Mindray biochemical analyzer, CL-50 urine analyzer. After the animals autopsy we determined organs’ coefficient (heart, lungs, spleen, liver, stomach, kidneys, adrenals.Results. While studying the ECG of female rats, amplitude of R wave increased after they got Glycelax in both doses. Female rats who got Vaseline oil this index decreased at minimum dose and increased at maximum dose. After Glycelax application, male rats had an increased activity of alanine aminotransferase. After Vaseline oil application at maximum dose, female rats had alkaline phosphatase activity lowered. Female rats, which got a maximum dose of Vaseline oil had a total protein lowered. Glycelax at maximum dose increased the content of bilirubin and its fractions in male and female rats, while Vaseline oil application at maximum dose increased the content of bilirubin in female rats. Male rats which got Glycelax had hemoglobin and hematocrit level increased.Conclusion. At long-term application of Vaseline oil, animals of both genders had heart disorders with possible development of arrhythmia, hepatotoxic effect, lipid exchange dysfunction. After excessive use of Glycelax the above mentioned is added with possible hemoglobin and rheological blood properties level decrease.

  4. A Comparative Study of Hollow Copper Sulfide Nanoparticles and Hollow Gold Nanospheres on Degradability and Toxicity

    Science.gov (United States)

    Guo, Liangran; Panderi, Irene; Yan, Daisy D.; Szulak, Kevin; Li, Yajuan; Chen, Yi-Tzai; Ma, Hang; Niesen, Daniel B.; Seeram, Navindra; Ahmed, Aftab; Yan, Bingfang; Pantazatos, Dionysios; Lu, Wei

    2013-01-01

    Gold and copper nanoparticles have been widely investigated for photothermal therapy of cancer. However, degradability and toxicity of these nanoparticles remain concerns. Here, we compare hollow CuS nanoparticles (HCuSNPs) with hollow gold nanospheres (HAuNS) in similar particle sizes and morphology following intravenous administration to mice. The injected pegylated HCuSNPs (PEG-HCuSNPs) are eliminated through both hepatobiliary (67 percentage of injected dose, %ID) and renal (23 %ID) excretion within one month post injection. By contrast, 3.98 %ID of Au is excreted from liver and kidney within one month after i.v. injection of pegylated HAuNS (PEG-HAuNS). Comparatively, PEG-HAuNS are almost non-metabolizable, while PEG-HCuSNPs are considered biodegradable nanoparticles. PEG-HCuSNPs do not show significant toxicity by histological or blood chemistry analysis. Principal component analysis and 2-D peak distribution plots of data from matrix-assisted laser desorption ionization-time of flight imaging mass spectrometry (MALDI-TOF IMS) of liver tissues demonstrated a reversible change in the proteomic profile in mice receiving PEG-HCuSNPs. This is attributed to slow dissociation of Cu ion from CuS nanoparticles along with effective Cu elimination for maintaining homeostasis. Nonetheless, an irreversible change in the proteomic profile is observed in the liver from mice receiving PEG-HAuNS by analysis of MALDI-TOF IMS data, probably due to the non-metabolizability of Au. This finding correlates with the elevated serum lactate dehydrogenase at 3 months after PEG-HAuNS injection, indicating potential long-term toxicity. The comparative results between the two types of nanoparticles will advance the development of HCuSNPs as a new class of biodegradable inorganic nanomaterials for photothermal therapy. PMID:24053214

  5. A comparative toxicity assessment of materials used in aquatic construction.

    Science.gov (United States)

    Lalonde, Benoit A; Ernst, William; Julien, Gary; Jackman, Paula; Doe, Ken; Schaefer, Rebecca

    2011-10-01

    Comparative toxicity testing was performed on selected materials that may be used in aquatic construction projects. The tests were conducted on the following materials: (1) untreated wood species (hemlock [Tsuga ssp], Western red cedar (Thuja plicata), red oak [Quercus rubra], Douglas fir [Pseudotsuga menziesii], red pine [Pinus resinosa], and tamarack [Larix ssp]); (2) plastic wood; (3) Ecothermo wood hemlock stakes treated with preservatives (e.g., chromated copper arsenate [CCA], creosote, alkaline copper quaternary [ACQ], zinc naphthenate, copper naphthenate, and Lifetime Wood Treatment); (4) epoxy-coated steel; (5) hot-rolled steel; (6) zinc-coated steel; and (7) concrete. Those materials were used in acute lethality tests with rainbow trout, Daphnia magna, Vibrio fischeri and threespine stickleback. The results indicated the following general ranking of the materials (from the lowest to highest LC(50) values); ACQ > creosote > zinc naphthenate > copper naphthenate > CCA (treated at 22.4 kg/m(3)) > concrete > red pine > western red cedar > red oak > zinc-coated steel > epoxy-coated steel > CCA (6.4 kg/m(3)). Furthermore, the toxicity results indicated that plastic wood, certain untreated wood species (hemlock, tamarack, Douglas fir, and red oak), hot-rolled steel, Ecothermo wood, and wood treated with Lifetime Wood Treatment were generally nontoxic to the test species.

  6. Comparative toxicity of pesticides to stingless bees (Hymenoptera: Apidae: Meliponini).

    Science.gov (United States)

    Valdovinos-Núñez, Gustavo Rafael; Quezada-Euán, José Javier G; Ancona-Xiu, Patricia; Moo-Valle, Humberto; Carmona, Angelica; Ruiz Sanchez, Esaú

    2009-10-01

    Stingless bees are potential pollinators of commercial tropical crops and their use may increase in the short term. However, studies comparing the toxicity of pesticides to different individuals and species are lacking, making it difficult to evaluate their short- and long-term effects on colonies and populations of these insects. In this work, we tested the lethality of compounds from the main pesticide groups on stingless bees of the species Melipona beecheii Bennett, Trigona nigra Provancher, and Nannotrigona perilampoides Cresson. The LDo (in micrograms per bee) for each pesticide was calculated for callow workers and foragers of the three species as well as for gynes and drones of M. beecheii. The results showed that all species were highly susceptible to the evaluated compounds. Nicotinoid pesticides were the most toxic, followed in descending order by permethrin, diazinon, and methomyl. We found evidence of a relationship between the body weight of the species and their LD50 for permethrin and methomyl (r = 0.91 and 0.90, respectively) but not for diazinon (r = -0.089). An analysis of contingency tables showed that within each species, callow workers had higher mortalities than foragers (P agriculture of Mexico and Latin America

  7. Comparative toxicity of copper nanoparticles across three Lemnaceae species.

    Science.gov (United States)

    Song, Lan; Vijver, Martina G; Peijnenburg, Willie J G M

    2015-06-15

    Metallic nanoparticles can end up in aquatic ecosystems due to their widespread application. Even though the toxicological effects of metallic nanoparticles to a diversity of species have been reported extensively, the toxicological data achieved in different studies are not always comparable and little is known regarding the comparative toxicity of nanoparticles across species, as different test strategies and endpoints were applied. To attempt to fill this knowledge gap, Spirodela polyrhiza, Lemna minor and Wolffia arrhiza were exposed to 25 nm spherical copper nanoparticles to investigate the inhibiting effect of copper nanoparticle suspensions across species at three endpoints: total frond area, frond number and dry weight based relative growth rate. The total frond area based relative growth rate was found to be the most sensitive endpoint, with an EC50 of 1.15±0.09 mg/L for S. polyrhiza, 0.84±0.12 mg/L for L. minor and 0.64±0.05 mg/L for W. arrhiza. Both the particles and the copper ions contributed to the inhibiting effects of copper nanoparticle suspensions at all endpoints studied. Dose-response related inhibiting effects caused by the copper ions were found at all endpoints studied, whereas the particles only showed dose-response related inhibiting effects on the total frond area based relative growth rate. This suggests that different physiological processes are involved in case of exposure to particles and copper ions. W. arrhiza was found to be the most sensitive species tested and S. polyrhiza was the least sensitive species tested, when the inhibiting effect was evaluated based on the relative growth rate calculated from total frond area. These findings exemplify the importance of identifying the suitable endpoints of toxicity assessment and considering the intrinsic differences between species when evaluating the toxicological profile of metallic nanoparticles across species. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Eruca sativa seeds possess antioxidant activity and exert a protective effect on mercuric chloride induced renal toxicity.

    Science.gov (United States)

    Sarwar Alam, M; Kaur, Gurpreet; Jabbar, Zoobi; Javed, Kaleem; Athar, Mohammad

    2007-06-01

    Mercuric chloride (HgCl(2)) is a well-known nephrotoxic agent. Increasing number of evidences suggest the role of oxidative stress in HgCl(2) induced nephrotoxicity. Eruca sativa is widely used in folklore medicines and has a good reputation as a remedy of renal ailments. In the present study, the antioxidant potential of ethanolic extract of E. sativa seeds was determined and its protective effect on HgCl(2) induced renal toxicity was investigated. The extract was found to possess a potent antioxidant effect, with a large amount of polyphenols and a high reducing ability. HPLC analysis of the extract revealed glucoerucin and flavonoids to be the major antioxidants present in it. E. sativa extract significantly scavenged several reactive oxygen species (ROS) and reactive nitrogen species (RNS). Feeding of the extract to rats afforded a significant protection against HgCl(2) induced renal toxicity. Subcutaneous administration of 4 mg/kg body weight HgCl(2) induced renal injury evident as a marked elevation in serum creatinine and blood urea nitrogen levels, and histopathological changes such as necrosis, oedema and congestion of stroma and glomeruli. Oxidative modulation of renal tissues following HgCl(2) exposure was evident from a significant elevation in lipid peroxidation and attenuation in glutathione (GSH) contents and activities of antioxidant enzymes viz., catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD) and glutathione reductase (GR). Oral administration of E. sativa extract to rats at a dose regimen: 50-200 mg/kg body weight for 7 days prior to HgCl(2) treatment significantly and dose dependently protected against alterations in all these diagnostic parameters. The data obtained in the present study suggests E. sativa seeds to possess a potent antioxidant and renal protective activity and preclude oxidative damage inflicted to the kidney.

  9. Value of scintimetry compared with histomorphology, parathormone assay, densitometry and radiology in renal osteopathy

    Energy Technology Data Exchange (ETDEWEB)

    Lingg, G.; Nebel, G.; Dorr, S.

    1982-01-01

    The value of scintimetry is compared with histomorphology, parathormone assay, densitometry and radiology in renal osteopathy. The distribution of sup(99m)Tc-Sn-MDP in the thigh was estimated according to two different indices in 60 normal patients, 21 patients undergoing haemodialysis and one who had had a renal transplant. Deviation of the indices in these patients from the normal are significant. The indices were correlated with respect to their accuracy in detecting renal osteopathy with histomorphometry (as the reference method), radiological diagnosis, densitometry, parathormone assay and other laboratory tests. Accuracy of the method is high and, like histomorphometry, is over 9O%.

  10. Body composition by computed tomography as a predictor of toxicity in patients with renal cell carcinoma treated with sunitinib.

    LENUS (Irish Health Repository)

    Cushen, Samantha J

    2014-04-21

    Sunitinib is a standard first-line option for metastatic renal cell carcinoma (mRCC). Body composition is a prognostic factor in cancer patients and patients with loss of skeletal muscle mass and fat-free mass (FFM) are prone to dose-limiting toxicity (DLT) during targeted drug therapy. We investigated whether body composition by computed tomography predicted DLT from sunitinib in mRCC.

  11. Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

    Directory of Open Access Journals (Sweden)

    Mohamed Aboubakr

    2014-01-01

    Full Text Available The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV and oral (PO dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β and mean residence time (MRT were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot in renal damaged ducks (0.20 L kg−1 h−1 was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1. Following PO administration, the peak serum concentration (Cmax was higher in renal damaged than in healthy ducks and was achieved at maximum time (tmax of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el at a significant slower rate (3.94 h in renal damaged than in healthy ducks (2.89 h. The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for Cmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.

  12. Comparative developmental toxicity of planar PCB congeners by egg injection

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, D.J.; Melancon, M.J.; Eisemann, J.D.; Klein, P.N. [National Biological Service, Laurel, MD (United States). Patuxent Environmental Science Center

    1995-12-31

    The utility of egg injection studies for predicting potential embryotoxicity of PCBs and TCDD compares favorably with feeding studies. The effects of PCB congeners 3,3{prime}4,4{prime}-tetraCB (PCB 77), 2,3,3{prime},4,4{prime}-pentaCB (PCB 105), 3,3{prime},4,4{prime},5-pentaCB (PCB 126) and 2,2{prime},4,4{prime},5,5{prime}-hexaCB (PCB 153) were examined on embryonic development in chickens (Gallus gallus), northern bobwhite (Colinus virginianus), American kestrels (Falco sparverius), and common terns (Sterna hirundo) through hatching following air cell injections on day 4. The estimated LD{sub 50}s for these congeners in chickens were approximately 0.4 ppb, 2.6 ppb, 3326 ppb, and greater than 14,000 ppb, respectively; low effect levels (10--20% embryonic mortality) were 0.2 ppb, 1.2 ppb, 900 ppb, and 14,000 ppb respectively. The estimated LD{sub 50} for PCB 126 was 48 ppb for bobwhite, 65 ppb for American kestrels, and 104 ppb for common terns. The estimated LD{sub 50} for PCB 77 was 688 ppb for American kestrels. one or more hepatic microsomal cytochrome P450-linked monooxygenases including ethoxyresorufin-O-deethylase was assayed for each species. For PCB 126, the order of responsiveness of cytochrome P450 induction was: chicken > common tern > American kestrel > bobwhite, with chicken being approximately 100 times more responsive than common tern. These values are compared to existing Toxic Equivalency Factors (TEFs) including bioassay-derived ones.

  13. Comparative toxicity of leachates from 52 textiles to Daphnia magna.

    Science.gov (United States)

    Dave, Göran; Aspegren, Pia

    2010-10-01

    The environmental aspects of textiles are very complex and include production, processing, transport, usage, and recycling. Textiles are made from a variety of materials and can contain a large number of chemicals. Chemicals are used during production of fibres, for preservation and colouring and they are released during normal wear and during washing. The aim of this study was to investigate the release to water of toxic chemicals from various textiles. Altogether 52 samples of textiles made from cotton (21), linen (4), cotton and linen (7), cellulose (3), synthetic fibres (7), cotton and synthetic fibres (8) and wool (2). Seven were eco-labelled. All textiles were cut into squares and placed into Petri dishes with 50 ml ISO test medium in a concentration series (4-256 cm(2)/50 ml) and tested for acute toxicity to Daphnia magna. Estimated EC50s were converted into weight/volume, and 48-h EC50s ranged between 182 g/L. It was not possible to detect any difference between fibre type and toxicity (ANOVA), but a significantly higher toxicity was found for printed versus unprinted cotton and cotton/linen textiles, while the opposite was found for synthetic textiles. Eco-labelled products were evenly distributed on a toxicity scale, which means that eco-labelling in its present form does not necessarily protect users or the environment from exposure to toxic chemicals. Therefore, the results from the present study suggest that bioassays and toxicity tests should become an integrated part of textile environmental quality control programs.

  14. (Toxic hepatitis and acute renal failure after inhalation of chloride solvents: report of one case (author's transl))

    Energy Technology Data Exchange (ETDEWEB)

    Teixido Planas, J.; Martinez-Castelao, A.; Romero Gonzalez, R.; Grino Boira, J.; Gonzalez Segura, C.; Caralps Riera, A.

    1981-06-25

    Due to a combination of ingested ethanol and inhaled trichloroethylene (Tri) a 28 year old man developed toxic hepatitis and acute oliguric renal failure, both of which had a favorable evolution. Tri has been described as a cause of hepatic disfunction and acute renal failure due to acute tubular necrosis, although some of the cases described are controversial, because Tri was either contaminated by other dissolvents or could not be proven pure, with the exception of one case. In many there was ethanol ingestion. The Tri inhaled by our patient was found to contain less than 1% of carbon tetrachloride (C-Tchl). This would suggest the C-Tchl to be responsible for the clinical picture although the combination Tri/ethanol cannot be discarded as the causal agent, due to the small amount of contaminant present.

  15. Fatal group A streptococcal necrotizing fasciitis and toxic shock syndrome in a patient with psoriasis and chronic renal impairment.

    Science.gov (United States)

    Chong, Alvin H; Burrows, Nigel P

    2002-08-01

    A 78-year-old woman presented with rapid onset of skin pain which evolved into oedema, discoloration and infarction. She was diagnosed with group A beta-haemolytic streptococcus (Streptococcus pyogenes) necrotizing fasciitis and streptococcal toxic shock syndrome. The patient had a past history of psoriasis and end-stage renal impairment. Despite treatment with multiple antibiotics in an intensive care unit, the skin infarction involving the upper trunk continued to expand and the patient died within 24 hours of hospital admission. Group A streptococcus and Staphylococcus aureus were cultured from a tissue biopsy. Renal failure and compromised skin barrier function are known to predispose to invasive streptococcal infections, but necrotizing fasciitis has only rarely been reported in association with psoriasis. This case illustrates the fulminant nature of the infection.

  16. A Comparative Study of Sonographic Grading of Renal Parenchymal Changes and Estimated Glomerular Filtration Rate (eGFR) using Modified Diet in Renal Disease Formula

    Science.gov (United States)

    Shivalli, Siddharudha; Pai, B.H. Santhosh; Acharya, Koteshwara Devadasa; Gopalakrishnan, Ravichandra; Srikanth, Vivek; Reddy, Vishwanath; Haris, Arafat

    2016-01-01

    Introduction The sonographic findings are of help in evaluating the nephrological diseases. Glomerular filtration rate is another parameter for assessing the reserved renal function and an indicator of prognosis. In clinical practice GFR estimation (eGFR) is done by using a mathematical formula. In our study, we compared the sonographic grading of renal parenchymal changes with eGFR calculated using Modified Diet in Renal Diseases formula based on serum creatinine, age, gender and ethnicity. Aim To evaluate the relevance of sonographic grading of renal parenchymal changes in assessing the severity of the renal disease and comparing it to the eGFR calculated using MDRD formula based on the age, gender and serum creatinine value of the patient. Materials and Methods The adult patients with suspected kidney disease referred for sonography of abdomen were our study participants. As per our study design following strict inclusion and exclusion criteria, patients were selected as study participants and for each of the patient’s renal parenchymal status, serum creatinine, age, gender and ethnicity were documented. Results A total of 70 patients were our study participants, out of which 67.1% were males and 32.9% were females. Our study showed a linear correlation between sonographic grading of renal parenchymal changes with eGFR. Conclusion We conclude that by evaluating the kidneys with sonography and calculating eGFR using MDRD formula the renal status will be more accurately interpreted. PMID:27042555

  17. Synthesis, Characterization and renal toxicity of ZnO and polyethylene glycol Coated ZnO nanoparticles

    Directory of Open Access Journals (Sweden)

    Banafsheh Raisi Dehkourdi

    2017-01-01

    Full Text Available Objective(s: The wide scale use of Zinc oxide nanoparticles (ZnO NPs in the consumer market world makes human beings more prone to the exposure to ZnO nanoparticles and its adverse effects. Therefore, the aim of the present study is to assess renal toxicity potential of ZnO and Polyethylene glycol Coated ZnO Nanoparticles in rat.Materials and Methods: Co-precipitation chemical method was used in order to synthesize ZnO nanoparticles. The synthesized nanoparticles were coated with PEG (Polyethylene glycol and the coating interactions were investigated by FTIR (Fourier Transform Infrared Spectroscopy. Structural properties of ZnO NPs were evaluated by TEM (Transmission Electron Microscope and XRD (X Ray Diffraction. Toxicity assessment of ZnO and PEG coated ZnO nanoparticles were studied in rat by intra peritoneal injections during a one-month. Renal factors (Creatinine, Uric acid and Blood Urea Nitrogen were measured 15 and 30 days post injection.Results: The synthesized nanoparticles were single phase and have spinel structure. Their size distribution was around 18 nm. Some kidney factors were changed due to the injection of both uncoated and coated nanoparticles (especially in groups received concentrations of more than 100 mg per kg of body weight. Renal factors changes were more considerable in groups received ZnO NPs in comparison with those received PEG coated ZnO NPs. Chemical toxicity studies showed that there was no irreversible effect in the groups received  concentrations less than 200 mg/kg (mg per kg of body weight.Conclusion: The results indicated that renal factors were changed during 15 days post injection, especially in groups received high doses (200 mg/kg. The results of measurements 30 days post injection showed less change in comparison with the control and this indicates that there was no irreversible effect on kidney. Moreover, PEG coated nanoparticles were less toxic in comparison with Uncoated ZnO NPs.

  18. Comparing mortality in renal patients on hemodialysis versus peritoneal dialysis using a marginal structural model.

    NARCIS (Netherlands)

    Wal, W.M. van der; Noordzij, M.; Dekker, F.W.; Boeschoten, E.W.; Krediet, R.T.; Korevaar, J.C.; Geskus, R.B.

    2010-01-01

    When comparing the causal effect of peritoneal dialysis (PD) and hemodialysis (HD) treatment on lowering mortality in renal patients, using observational data, it is necessary to adjust for different forms of confounding and informative censoring. Both the type of dialysis treatment that is started

  19. A practical ranking system to compare toxicity of anti-fouling paints.

    Science.gov (United States)

    Karlsson, Jenny; Breitholtz, Magnus; Eklund, Britta

    2006-12-01

    The toxicity of a number of new anti-fouling paints, claimed to function by physical means and not by leakage of toxic substances, have been tested on two common organisms in the Baltic Sea, i.e., the red macro alga Ceramium tenuicorne and the copepod Nitocra spinipes. In order to compare the toxicity between the paints a ranking system was developed based on the EC(50)- and LC(50)-values. The results showed a wide span in toxicity with the most toxic paints ranked 160 times more toxic than the ones ranked least toxic. Also, TBT, irgarol and diuron, which have been used as active ingredients in traditional anti-fouling paints, were used to evaluate the sensitivity of the two test organisms. The results showed that the test organisms were equally sensitive to the substances as similar organisms in earlier studies. In conclusion, the ranking system presented in this study permits ranking and comparison of total toxicity of complex mixtures.

  20. Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat.

    OpenAIRE

    Agmon, Y; Peleg, H; Greenfeld, Z; Rosen, S.; Brezis, M

    1994-01-01

    Human radiocontrast nephrotoxicity is predicted by the presence of multiple risk factors, often associated with compromised renal circulation. To produce a simple model of radiocontrast nephropathy, rats were pretreated with indomethacin and N omega-nitro-L-arginine methyl ester (L-NAME, to inhibit nitric oxide synthesis) before the administration of iothalamate. Acute renal failure consistently developed, with a decline in creatinine clearance from 1.05 +/- 0.10 to 0.27 +/- 0.05 ml/min (P < ...

  1. Papillary and Nonpapillary Calcium Oxalate Monohydrate Renal Calculi: Comparative Study of Etiologic Factors

    Directory of Open Access Journals (Sweden)

    Enrique Pieras

    2006-01-01

    Full Text Available Calcium oxalate monohydrate (COM renal calculi can be classified into two groups: papillary and nonpapillary. In this paper, a comparative study between etiologic factors of COM papillary and nonpapillary calculi is performed. The study included 40 patients with COM renal calculi. The urine of these individuals was analyzed. Case history, lifestyle, and dietetic habits were obtained.No significant differences between urinary biochemical data of both groups were observed; 50% of COM papillary stone formers and 40% of COM nonpapillary stone formers had urolithiasis family history. A low consumption of phytate-rich products was observed for both groups. A relationship between profession with occupational exposure to cytotoxic products and COM papillary renal lithiasis was detected.The results suggest that COM papillary calculi would be associated to papillary epithelium alterations together with a crystallization inhibitors deficit, whereas COM nonpapillary calculi would be associated to the presence of heterogeneous nucleants and a crystallization inhibitors deficit.

  2. Comparative toxicity of eight metals on freshwater fish.

    Science.gov (United States)

    Shuhaimi-Othman, Mohammad; Yakub, Nadzifah; Ramle, Nur-Amalina; Abas, Ahmad

    2015-09-01

    Two freshwater fish, Rasbora sumatrana (Cyprinidae) and Poecilia reticulata (guppy; Poeciliidae), were exposed to a range of eight heavy metals (copper (Cu), cadmium (Cd), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), aluminium (Al), and manganese (Mn)) at varied concentrations for 96 h in the laboratory. Mortality was assessed and median lethal concentrations (LC50) were calculated. It was observed that the LC50 values increased with a decrease in mean exposure times, for all metals and for both fish types. The 96-h LC50 values for Cu, Cd, Zn, Pb, Ni, Fe, Al, and Mn were 0.006, 0.10, 0.46, 0.63, 0.83, 1.71, 1.53, and 5.71 mg/L for R. sumatrana and 0.038, 0.17, 1.06, 1.99, 15.62, 1.46, 6.76, and 23.91 mg/L for P. reticulata, respectively. The metal toxicity trend for R. sumatrana and P. reticulata from most to least toxic was Cu > Cd > Zn > Pb > Ni > Al > Fe > Mn and Cu > Cd > Zn > Fe > Pb > Al > Ni > Mn, respectively. Results indicated that Cu was the most toxic metal on both fish, and R. sumatrana was more sensitive than P. reticulata to all the eight metals.

  3. Comparative developmental toxicity of environmentally relevant oxygenated PAHs

    Energy Technology Data Exchange (ETDEWEB)

    Knecht, Andrea L., E-mail: andrea.knecht@tanguaylab.com [Department of Environmental and Molecular Toxicology, the Environmental Health Sciences Center, Oregon State University, Corvallis, OR (United States); Goodale, Britton C., E-mail: goodaleb@onid.orst.edu [Department of Environmental and Molecular Toxicology, the Environmental Health Sciences Center, Oregon State University, Corvallis, OR (United States); Truong, Lisa, E-mail: lisa.truong.888@gmail.com [Department of Environmental and Molecular Toxicology, the Environmental Health Sciences Center, Oregon State University, Corvallis, OR (United States); Simonich, Michael T., E-mail: mtsimonich@oregonstate.edu [Department of Environmental and Molecular Toxicology, the Environmental Health Sciences Center, Oregon State University, Corvallis, OR (United States); Swanson, Annika J., E-mail: swansoan@onid.orst.edu [Department of Environmental and Molecular Toxicology, the Environmental Health Sciences Center, Oregon State University, Corvallis, OR (United States); Matzke, Melissa M., E-mail: melissa.matzke@pnl.gov [Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, WA (United States); Anderson, Kim A., E-mail: kim.anderson@oregonstate.edu [Department of Environmental and Molecular Toxicology, the Environmental Health Sciences Center, Oregon State University, Corvallis, OR (United States); Waters, Katrina M., E-mail: katrina.waters@pnl.gov [Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, WA (United States); Tanguay, Robert L., E-mail: robert.tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, the Environmental Health Sciences Center, Oregon State University, Corvallis, OR (United States)

    2013-09-01

    Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are byproducts of combustion and photo-oxidation of parent PAHs. OPAHs are widely present in the environment and pose an unknown hazard to human health. The developing zebrafish was used to evaluate a structurally diverse set of 38 OPAHs for malformation induction, gene expression changes and mitochondrial function. Zebrafish embryos were exposed from 6 to 120 h post fertilization (hpf) to a dilution series of 38 different OPAHs and evaluated for 22 developmental endpoints. AHR activation was determined via CYP1A immunohistochemistry. Phenanthrenequinone (9,10-PHEQ), 1,9-benz-10-anthrone (BEZO), xanthone (XAN), benz(a)anthracene-7,12-dione (7,12-B[a]AQ), and 9,10-anthraquinone (9,10-ANTQ) were evaluated for transcriptional responses at 48 hpf, prior to the onset of malformations. qRT-PCR was conducted for a number of oxidative stress genes, including the glutathione transferase(gst), glutathione peroxidase(gpx), and superoxide dismutase(sod) families. Bioenergetics was assayed to measure in vivo oxidative stress and mitochondrial function in 26 hpf embryos exposed to OPAHs. Hierarchical clustering of the structure-activity outcomes indicated that the most toxic of the OPAHs contained adjacent diones on 6-carbon moieties or terminal, para-diones on multi-ring structures. 5-carbon moieties with adjacent diones were among the least toxic OPAHs while the toxicity of multi-ring structures with more centralized para-diones varied considerably. 9,10-PHEQ, BEZO, 7,12-B[a]AQ, and XAN exposures increased expression of several oxidative stress related genes and decreased oxygen consumption rate (OCR), a measurement of mitochondrial respiration. Comprehensive in vivo characterization of 38 structurally diverse OPAHs indicated differential AHR dependency and a prominent role for oxidative stress in the toxicity mechanisms. - Highlights: • OPAHs are byproducts of combustion present in the environment. • OPAHs pose a largely

  4. Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells

    Directory of Open Access Journals (Sweden)

    Nadine Gelbrich

    2017-01-01

    Full Text Available Objective. Cytokines and chemokines are widely involved in cancer cell progression and thus represent promising candidate factors for new biomarkers. Methods. Four renal cell cancer (RCC cell lines (Caki-1, 786-O, RCC4, and A498 and a nonmalignant renal cell line (RC-124 were examined with respect to their proliferation. The cytokine and chemokine expression pattern was examined by a DNA array (Human Cytokines & Chemokines RT2 Profiler PCR Array; Qiagen, Hilden, Germany, and expression profiles were compared. Results. Caki-1 and 786-O cells exhibited significantly increased proliferation rates, whereas RCC4 and A498 cells demonstrated attenuated proliferation, compared to nonmalignant RC-124 cells. Expression analysis revealed 52 cytokines and chemokines primarily involved in proliferation and inflammation and differentially expressed not only in malignant and nonmalignant renal cells but also in the four RCC cell lines. Conclusion. This is the first study examining the expression of 84 cytokines and chemokines in four RCC cell lines compared to that in a nonmalignant renal cell line. VEGFA, NODAL, and BMP6 correlated with RCC cell line proliferation and, thus, may represent putative clinical biomarkers for RCC progression as well as for RCC diagnosis and prognosis.

  5. Comparative analysis of maximum renal longitudinal length with positional changes on ultrasound with multiplanar reconstructed MR image in Korea Adults

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Yun Hee; Cho, Bum Sang; Kang, Min Ho; Kang, Woo Young; Lee, Jisun; Kim, Yook; Lee, Soo Hyun; Lee, Soo Jung [Dept. of Radiology, Chungbuk National University Hospital, Cheongju (Korea, Republic of); Lee, Jin Yong [Public Health Medical Service, Seoul National University Boramae Medical Center, Seoul (Korea, Republic of)

    2016-07-15

    The purpose of this study was to determine a suitable position in which the measured length on ultrasound is close to the true renal length obtained through a multiplanar reconstructed MR image. A total of 33 individuals (males: 15, females: 18) without any underlying renal disease were included in the present study. Renal length was measured as the longest axis at the level of the renal hilum in three positions-supine, lateral decubitus, and prone, respectively. With a 3.0 T MR scanner, 3D eTHRIVE was acquired. Subsequently, the maximum longitudinal length of both the kidneys was measured through multiplanar reconstructed MR images. Paired t-test was used to compare the renal length obtained from ultrasonographic measurement with the length obtained through multiplanar reconstructed MR images. Our study demonstrated significant difference between sonographic renal length in three positions and renal length through MRI (p < 0.001). However, the longest longitudinal length of right kidney among the measured three values by ultrasound was statistically similar to the renal length measured by reconstructed MR image. Among them, the lateral decubitus position showed the strongest correlation with true renal length (right: 0.887; left: 0.849). We recommend measurement of the maximum renal longitudinal length in all possible positions on ultrasonography. If not allowed, the best measurement is on the lateral decubitus showing the strongest correlation coefficient with true renal length.

  6. Human renal tubular cells contain CD24/CD133 progenitor cell populations: Implications for tubular regeneration after toxicant induced damage using cadmium as a model.

    Science.gov (United States)

    Shrestha, Swojani; Somji, Seema; Sens, Donald A; Slusser-Nore, Andrea; Patel, Divyen H; Savage, Evan; Garrett, Scott H

    2017-09-15

    The proximal tubules of the kidney are target sites of injury by various toxicants. Cadmium (Cd(+2)), an environmental nephrotoxicant can cause adverse effects and overt renal damage. To decipher the mechanisms involved in nephrotoxicity, an in vitro model system is required. Mortal cultures of human proximal tubule (HPT) cells have served, as models but are difficult to acquire and do not lend themselves to stable transfection. The immortalized human proximal tubule cell line HK-2, has served as a model but it lacks vectorial active transport and shows signs of lost epithelial features. Recently a new proximal tubule cell line was developed, the RPTEC/TERT1, and the goal of this study was to determine if this cell line could serve as a model to study nephrotoxicity. Global gene expression analysis of this cell line in comparison to the HK-2 and HPT cells showed that the RPTEC/TERT1 cells had gene expression patterns similar to HPT cells when compared to the HK-2 cells. The HPT and the RPTEC/TERT1 cell line had an increased population of stem/progenitor cells co-expressing CD24 and CD133 when compared to the HK-2 cells. The level of expression of cadherins, claudins and occludin molecules was also similar between the RPTEC/TERT1 and the HPT cells. Acute exposure to Cd(+2) resulted in necrosis of the RPTEC/TERT1 cells when compared to the HK-2 cells which died by apoptosis. Thus, the RPTEC/TERT1 cells are similar to HPT cells and can serve as a good model system to study mechanisms involved in toxicant induced renal damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A Case of Severe Hydroxychloroquine-Induced Retinal Toxicity in a Patient with Recent Onset of Renal Impairment: A Review of the Literature on the Use of Hydroxychloroquine in Renal Impairment

    Directory of Open Access Journals (Sweden)

    Rajen Tailor

    2012-01-01

    Full Text Available We present a case of a 67-year-old female who presented with a twelve-month history of progressive blurred vision in both eyes. The patient was on hydroxychloroquine 200 mg twice a day for eight years for the treatment of scarring alopecia. Two years prior to presenting, the patient was found to have chronic kidney disease stage 3 secondary to hypertension. Examination revealed bilateral reduced visual acuities with attenuated arterioles and pigmentary changes on retinal assessment. Goldmann visual fields showed grossly constricted fields in both eyes. The patient was diagnosed with retinal toxicity secondary to hydroxychloroquine probably potentiated by renal impairment. Risk factors for retinal toxicity secondary to hydroxychloroquine can be broadly divided into dose-related and patient-related factors. Our patient developed severe retinal toxicity despite being on the recommended daily dose (400 mg per day. Although retinal toxicity at this dose has been documented, the development of renal impairment without dose adjustment or close monitoring of visual function is likely to have potentiated retinal toxicity. This case highlights the need to monitor renal function in patients on hydroxychloroquine. Should renal impairment develop, either the drug should be stopped or the dose reduced with close monitoring of visual function by an ophthalmologist.

  8. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity.

    Science.gov (United States)

    Niu, Ying-Mei; Zhu, Xiao-Li; Chang, Bing; Tong, Zhao-Hui; Cao, Wen; Qiao, Pei-Huan; Zhang, Lin-Yuan; Zhao, Jing; Song, Yu-Guo

    2016-01-01

    We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity.

  9. Comparative gene expression in toxic versus non-toxic strains of the marine dinoflagellate Alexandrium minutum

    Directory of Open Access Journals (Sweden)

    Glöckner Gernot

    2010-04-01

    Full Text Available Abstract Background The dinoflagellate Alexandrium minutum typically produces paralytic shellfish poisoning (PSP toxins, which are known only from cyanobacteria and dinoflagellates. While a PSP toxin gene cluster has recently been characterized in cyanobacteria, the genetic background of PSP toxin production in dinoflagellates remains elusive. Results We constructed and analysed an expressed sequence tag (EST library of A. minutum, which contained 15,703 read sequences yielding a total of 4,320 unique expressed clusters. Of these clusters, 72% combined the forward-and reverse reads of at least one bacterial clone. This sequence resource was then used to construct an oligonucleotide microarray. We analysed the expression of all clusters in three different strains. While the cyanobacterial PSP toxin genes were not found among the A. minutum sequences, 192 genes were differentially expressed between toxic and non-toxic strains. Conclusions Based on this study and on the lack of identified PSP synthesis genes in the two existent Alexandrium tamarense EST libraries, we propose that the PSP toxin genes in dinoflagellates might be more different from their cyanobacterial counterparts than would be expected in the case of a recent gene transfer. As a starting point to identify possible PSP toxin-associated genes in dinoflagellates without relying on a priori sequence information, the sequences only present in mRNA pools of the toxic strain can be seen as putative candidates involved in toxin synthesis and regulation, or acclimation to intracellular PSP toxins.

  10. Increased risk of dialysis and end-stage renal disease among HIV patients in Denmark compared with the background population

    DEFF Research Database (Denmark)

    Rasch, Magnus G; Helleberg, Marie; Feldt-Rasmussen, Bo;

    2014-01-01

    BACKGROUND: HIV patients have increased risk of impaired renal function. We aimed to estimate the incidence of any renal replacement therapy (aRRT) and start of chronic renal replacement therapy (cRRT) among HIV patients compared with population controls. METHODS: In a nationwide, population...... with the background population. We found no association between exposure to tenofovir, atazanavir or the combination of the two and risk of aRRT or cRRT....

  11. Minimal renal toxicity after Rituximab DHAP with a modified cisplatin application scheme in patients with relapsed or refractory diffuse large B-cell lymphoma

    OpenAIRE

    Lisenko, Katherina; McClanahan, F.; Schöning, Tilman; Schwarzbich, Mark Alexander; Cremer, Martin; Dittrich, Tobias; Ho, Anthony D; Witzens-Harig, Mathias

    2016-01-01

    Background: Rituximab (R) in combination with DHAP is a widely accepted salvage regimen for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). A common adverse effect of this protocol is renal toxicity which may result in treatment discontinuation. Assuming that a lower single dose of cisplatin over several days would reduce renal toxicity, our institution has chosen to administer cisplatin in a dosage of 25 mg/m2 per day as a 3-h infusion over 4 consecutive days. M...

  12. Comparative toxicities of organophosphate and pyrethroid insecticides to aquatic macroarthropods.

    Science.gov (United States)

    Halstead, Neal T; Civitello, David J; Rohr, Jason R

    2015-09-01

    As agricultural expansion and intensification increase to meet the growing global food demand, so too will insecticide use and thus the risk of non-target effects. Insecticide pollution poses a particular threat to aquatic macroarthropods, which play important functional roles in freshwater ecosystems. Thus, understanding the relative toxicities of insecticides to non-target functional groups is critical for predicting effects on ecosystem functions. We exposed two common macroarthropod predators, the crayfish Procambarus alleni and the water bug Belostoma flumineum, to three insecticides in each of two insecticide classes (three organophosphates: chlorpyrifos, malathion, and terbufos; and three pyrethroids: esfenvalerate, λ-cyhalothrin, and permethrin) to assess their toxicities. We generated 150 simulated environmental exposures using the US EPA Surface Water Contamination Calculator to determine the proportion of estimated peak environmental concentrations (EECs) that exceeded the US EPA level of concern (0.5×LC50) for non-endangered aquatic invertebrates. Organophosphate insecticides generated consistently low-risk exposure scenarios (EECs0.5×LC50) to P. alleni, but not to B. flumineum, where only λ-cyhalothrin produced consistently high-risk exposures. Survival analyses demonstrated that insecticide class accounted for 55.7% and 91.1% of explained variance in P. alleni and B. flumineum survival, respectively. Thus, risk to non-target organisms is well predicted by pesticide class. Identifying insecticides that pose low risk to aquatic macroarthropods might help meet increased demands for food while mitigating against potential negative effects on ecosystem functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Comparative toxicities of novel and conventional acaricides against different stages

    Directory of Open Access Journals (Sweden)

    Sapana Kumari

    2017-04-01

    Full Text Available Adulticidal, ovicidal and nymphicidal effects of different newer acaricides along with some conventional one were evaluated on the life stages of a susceptible laboratory strain of two-spotted spider mite (TSMM, Tetranychus urticae Koch (Acarina: Tetranychidae using a spray method. Abamectin was found to be the most toxic to the adults (LC50 = 0.39 ppm followed by fenpyroximate (5.67 ppm, spiromesifen (12.53 ppm, chlorfenapyr (32.24 ppm, propargite (77.05 ppm and dicofol (146.65 ppm. Hexythiazox was least toxic. There was no egg hatching when eggs were sprayed with one third of the recommended concentration of spiromesifen. This was statistically significantly different from all other treatments (fenpyroximate, chlorfenapyr, propargite, dicofol and hexythiazox which were, however, at par with each other. Based on the 10th day observations, the ovicidal activity of spiromesifen (100% was followed by dicofol (7.78% egg mortality and hexythiazox (6.67%. Almost no effect on hatching was observed in both abamectin and chlorfenapyr treatment (0.54%. In case of propargite, all the treated eggs hatched. Abamectin resulted in highest nymphal mortality (96.05% followed by dicofol (94.51%, hexythiazox (90.24 propargite (90.00, chlorfenapyr (89.33 and fenpyroximate (86.84% and all the treatments were at par with each other and statistically different from the control. The present study revealed that abamectin, spiromesifen, hexythiazox, fenpyroximate and chlorfenapyr acaricides can alternatively be used for effective management of the mites.

  14. Strain-specific renal toxicity of heterologous antilymphocyte [gamma]-globulin in mice7

    NARCIS (Netherlands)

    Cohen, B.J.; Vries, M.J. de; Noord, M.J. van; Lubbe, F.H.

    1970-01-01

    Severe glomerulonephritis followed one to five weekly i.p. injections in TLFM mice of rabbit antimouse lymphocyte [gamma]-globulin (ALG). Glomerulonephritis did not occur in C57BL mice subjected to the same regimen. Administration of normal rabbit [gamma]-globulin (NRG) to RFM mice also caused renal

  15. Biotransformation, transport and toxicity studies in rat renal proximal tubular cells.

    NARCIS (Netherlands)

    Haenen, H.E.M.G.

    1996-01-01

    SummaryRenal proximal tubular (RPT) cells can be exposed apically to glomerulary filtrated and basolaterally to non-filtrated nephrotoxic compounds. To excrete these compounds via the urine, RPT cells are equipped with transport systems able to transport nephrotoxicants from the basolateral to the a

  16. Strain-specific renal toxicity of heterologous antilymphocyte [gamma]-globulin in mice7

    NARCIS (Netherlands)

    Cohen, B.J.; Vries, M.J. de; Noord, M.J. van; Lubbe, F.H.

    1970-01-01

    Severe glomerulonephritis followed one to five weekly i.p. injections in TLFM mice of rabbit antimouse lymphocyte [gamma]-globulin (ALG). Glomerulonephritis did not occur in C57BL mice subjected to the same regimen. Administration of normal rabbit [gamma]-globulin (NRG) to RFM mice also caused renal

  17. Comparative toxicity of some detergents on an estuarine fish, Ambassis commersonii

    OpenAIRE

    1988-01-01

    The comparative toxicity was evaluated using four detergents, viz, linear alkylbenzene sulfonate (LAS), branched alkylbenzene sulfonate (BAS), sodium sulfonate (SS) and alfa-olefin sulfonate (AOS) on an estuarine fish, Ambassis commersonii, abundant in Kali estuarine system. Standard toxicity bioassay method was followed as per APHA (1980). AOS concentration in "Mega" soap was determined by the standard MBAS method described in APHA (1980). The results indicate that LAS was the most toxic det...

  18. Optimized conformal paraaortic lymph node irradiation is not associated with enhanced renal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Nevinny-Stickel, M.; Forthuber, B.C.; Posch, A.; Beer, B.; Lukas, P.; Seppi, T. [Innsbruck Medical Univ. (Austria). Dept. of Therapeutic Radiology and Oncology; Poljanc, K. [Technische Univ. Vienna (Austria). Atomic Inst. of the Austrian Universities; Heute, D. [Innsbruck Medical Univ. (Austria). Dept. of Nuclear Medicine; Lechner, J. [Innsbruck Medical Univ. (Austria). Div. of Physiology

    2007-07-15

    Background and Purpose: For patients with gynecologic carcinomas, irradiation of paraaortic lymph nodes (PLNs) is a routine treatment concept. Planning target volumes (PTVs) individually optimized by radiation field delineations along the big vessels permit the inclusion of at least 97% of potentially involved PLNs. However, this novel treatment technique might increase radiation-induced nephrotoxicity. Therefore, the actual incidence of kidney damage after PLN irradiation has to be assessed in order to validate the safety of this treatment concept. Patients and Methods: 19 patients were treated with irradiation alone (50.4 Gy; 5 x 1.8 Gy/week) and monitored for up to 90 months. Functional renal parameters, namely renal plasma flow (RPF) and glomerular filtration rate (GFR), were assessed by dynamic renal scintigraphy. Additionally, patients were clinically observed (i.e., hypertension, proteinuria) and calculations of normal-tissue complication probability (NTCP) values for nonuniform kidney irradiation were performed using the Lyman-Wolbarst algorithm. Results: Two patients with anticipated moderate NTCP values (12.6% and 8.7%) showed slightly impaired RPF rates at 12, 24, and after 48 months of follow-up. Only one patient in the subgroup showing NTCP values > 50% (n = 9) developed a notable impairment of renal RPF. However, all patients including those with elevated complication probabilities exhibited neither impaired GFR nor clinically apparent symptoms related to a loss of functioning renal tissue from 12 to > 48 months post irradiation. Conclusion: Conformal irradiation of retroperitoneal lymph nodes with individual PTV delineation appears not to be associated with clinically relevant functional impairment of the kidneys. (orig.)

  19. JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin.

    Science.gov (United States)

    Qiu, Mingning; Ke, Longzhi; Zhang, Sai; Zeng, Xin; Fang, Zesong; Liu, Jianjun

    2017-08-01

    Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

  20. Assessment of Metal Toxicity in Marine Ecosystems: Comparative Toxicity Potentials for Nine Cationic Metals in Coastal Seawater

    DEFF Research Database (Denmark)

    Dong, Yan; Rosenbaum, Ralph K.; Hauschild, Michael Zwicky

    2016-01-01

    This study is a first attempt to develop globally applicable and spatially differentiated marine Comparative Toxicity Potentials (CTPs) or ecotoxicity characterization factors for metals in coastal seawater for use in Life Cycle Assessment. The toxicity potentials are based exclusively on marine...... varies 3-4 orders of magnitude across LMEs, largely due to different seawater residence time. Therefore the highest toxicity potential for metals was found in the LMEs with the longest seawater residence times. Across metals, the highest CTPs were observed for Cd, Pb and Zn. At the concentration levels...... ecotoxicity data and take account of metal speciation and bioavailability. CTPs were developed for nine cationic metals (Cd, Cr(III), Co, Cu(II), Fe(III), Mn, Ni, Pb and Zn) in 64 Large Marine Ecosystems (LMEs) covering all coastal waters in the world. The results showed that the CTP of a specific metal...

  1. Comparative chronic toxicity of imidacloprid, clothianidin, and thiamethoxam to Chironomus dilutus and estimation of toxic equivalency factors.

    Science.gov (United States)

    Cavallaro, Michael C; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

    2017-02-01

    Nontarget aquatic insects are susceptible to chronic neonicotinoid insecticide exposure during the early stages of development from repeated runoff events and prolonged persistence of these chemicals. Investigations on the chronic toxicity of neonicotinoids to aquatic invertebrates have been limited to a few species and under different laboratory conditions that often preclude direct comparisons of the relative toxicity of different compounds. In the present study, full life-cycle toxicity tests using Chironomus dilutus were performed to compare the toxicity of 3 commonly used neonicotinoids: imidacloprid, clothianidin, and thiamethoxam. Test conditions followed a static-renewal exposure protocol in which lethal and sublethal endpoints were assessed on days 14 and 40. Reduced emergence success, advanced emergence timing, and male-biased sex ratios were sensitive responses to low-level neonicotinoid exposure. The 14-d median lethal concentrations for imidacloprid, clothianidin, and thiamethoxam were 1.52 μg/L, 2.41 μg/L, and 23.60 μg/L, respectively. The 40-d median effect concentrations (emergence) for imidacloprid, clothianidin, and thiamethoxam were 0.39 μg/L, 0.28 μg/L, and 4.13 μg/L, respectively. Toxic equivalence relative to imidacloprid was estimated through a 3-point response average of equivalencies calculated at 20%, 50%, and 90% lethal and effect concentrations. Relative to imidacloprid (toxic equivalency factor [TEF] = 1.0), chronic (lethality) 14-d TEFs for clothianidin and thiamethoxam were 1.05 and 0.14, respectively, and chronic (emergence inhibition) 40-d TEFs were 1.62 and 0.11, respectively. These population-relevant endpoints and TEFs suggest that imidacloprid and clothianidin exert comparable chronic toxicity to C. dilutus, whereas thiamethoxam induced comparable effects only at concentrations an order of magnitude higher. However, the authors caution that under field conditions, thiamethoxam readily degrades to

  2. A Comparative Study on Several Models of Experimental Renal Calcium Oxalate Stones Formation in Rats

    Institute of Scientific and Technical Information of China (English)

    LIU Jihong; CAO Zhenggno; ZHANG Zhaohui; ZHOU Siwei; YE Zhangqun

    2007-01-01

    In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D3 [1α(OH)VitD3, alfacalcidol], calcium gluconate, ammonium oxalate, gentamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate excretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG+L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG+L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D3, the deposition of calcium oxalate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group induced by EG plus Vitamin D3. EG plus Vitamin D3 or EG plus AC could stably and significantly induced the rat model of renal calcium oxalate stones formation.

  3. Phlorizin pretreatment reduces acute renal toxicity in a mouse model for diabetic nephropathy.

    Science.gov (United States)

    Brouwers, Bas; Pruniau, Vincent P E G; Cauwelier, Elisa J G; Schuit, Frans; Lerut, Evelyne; Ectors, Nadine; Declercq, Jeroen; Creemers, John W M

    2013-09-20

    Streptozotocin (STZ) is widely used as diabetogenic agent in animal models for diabetic nephropathy (DN). However, it is also directly cytotoxic to kidneys, making it difficult to distinguish between DN-related and STZ-induced nephropathy. Therefore, an improved protocol to generate mice for DN studies, with a quick and robust achievement of the diabetic state, without direct kidney toxicity is required. To investigate the mechanism leading to STZ-induced nephropathy, kidney damage was induced with a high dose of STZ. This resulted in delayed gastric emptying, at least partially caused by impaired desacyl ghrelin clearance. STZ uptake in the kidneys is to a large extent mediated by the sodium/glucose cotransporters (Sglts) because the Sglt inhibitor phlorizin could reduce STZ uptake in the kidneys. Consequently, the direct toxic effects in the kidney and the gastric dilatation were resolved without interfering with the β-cell toxicity. Furthermore, pancreatic STZ uptake was increased, hereby decreasing the threshold for β-cell toxicity, allowing for single low non-nephrotoxic STZ doses (70 mg/kg). In conclusion, this study provides novel insights into the mechanism of STZ toxicity in kidneys and suggests a more efficient regime to induce DN with little or no toxic side effects.

  4. Once-daily oral administration of cyclosporine in a lung transplant patient with a history of renal toxicity of calcineurin inhibitors.

    Science.gov (United States)

    Matsuda, Yuya; Chen, Fengshi; Miyata, Hitomi; Date, Hiroshi

    2014-07-01

    Cyclosporine is usually administered orally in two divided doses every 12 h in transplant patients. However, some patients have difficulty in achieving therapeutic levels after transplantation. In fact, cyclosporine is reportedly administered once daily in renal and liver transplantation cases, but not in lung transplantation cases. We report a patient with a history of calcineurin inhibitor-induced renal toxicity who successfully underwent living-donor lobar lung transplantation (LDLLT) with the novel immunosuppressive strategy of once-daily administration of cyclosporine. An 18-year old man with progressive respiratory insufficiency after bone marrow transplantation was referred to our hospital for lung transplantation. He had a history of renal toxicity due to calcineurin inhibitors. Based on his history of tacrolimus- and cyclosporine-induced renal toxicity, we decided to initiate basiliximab as induction therapy, followed by once-daily cyclosporine administration to obtain high enough blood cyclosporine concentrations at 2 h post-dose (C2) and lowered trough blood concentrations (C0) for protection of renal function as maintenance therapy. LDLLT was successfully performed, and the postoperative course was uneventful and free of rejection episodes. Cyclosporine dosing was adjusted with intensive therapeutic drug monitoring of blood cyclosporine levels. One year after LDLLT, the patient is alive and well with no problems with daily life activities. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  5. Cymbopogon citratus protects against the renal injury induced by toxic doses of aminoglycosides in rabbits

    Directory of Open Access Journals (Sweden)

    N Ullah

    2013-01-01

    Full Text Available Renal injury is the most common side-effect of aminoglycosides. These antimicrobial drugs are particularly effective against Gram-negative microorganisms. The present study was conducted to investigate the renal protective activity of Cymbopogon citratus in gentamicin-induced nephrotoxicity. Male rabbits were divided into four groups (n=6 including group 1 (0.9% saline treated, group 2 (80 mg/kg/day gentamicin-treated, group 3 (200 mg/kg/day Cymbopogon citratus treated and group 4 (80 mg/kg/day gentamicin and 200 mg/kg/day Cymbopogon citratus treated. Biochemical kidney functioning parameters, urinary enzymes and histopathological examination were performed. The results of the present study showed that simultaneous administration of Cymbopogon citrates and gentamicin significantly protected alteration in body weight, blood urea nitrogen, serum creatinine, creatinine clearance, serum uric acid, serum electrolytes, urinary volume, urinary protein, urinary lactate dehydrogenase and urinary alkaline phosphatase induced by gentamicin. Histological examination of the kidney also suggested the same. It is concluded from the current study that co-administration of Cymbopogon citratus with gentamicin for 3 weeks successfully prevented renal damage associated with aminoglycosides.

  6. Comparative study of renal sodium transport between ouabain-hypertensive rats and ouabain-nonhypertensive rats

    Institute of Scientific and Technical Information of China (English)

    GE Heng; Lü Zhuo-ren

    2006-01-01

    Objective: To compare renal sodium transport, using fractional excretions of lithium(FEii)as a marker of proximal tubule sodium reabsorption, between hypertensive and non-hypertensive ouabaintreated rats and further to elucidate the role of ouabain in pathogenesis of hypertension. Methods:Thirty male Sprague-Dawley rats weighting 180-200 g were randomly divided into normal control group and ouabain treated group. Rats were infused with 1 ml/kg · d normal saline or 27.8 μg/kg · d ouabain intraperitoneally once a day respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Rats were sacrificed 6 weeks after treatment. Blood and 24-hour urine sample were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated.Ouabain levels of plasma and renal tissue, plasma renin activity, angiotensin Ⅱ and aldosterone concentration were determined. Results: 65% of the ouabain-treated rats achieved significantly higher SBP after 4weeks, compared with that of the saline control groups or self baseline (P<0. 01). But in the other 35%of the ouabain-treated rats, their SBP was similar with control group during the experiment (P>0. 05).The body weight, heart rate and food intake between the 3 groups were no significant differences (P>0.05). FELi and FDRNa were significantly lower in ouabain-hypertensive group compared with ouabain-nonhypertensive group and control group(P<0.01 and P<0.05). The FELi and FDRNa of ouabain-nonhypertensive groups were similar with control group(P>0.05). Ccr and FENa were comparable between the 3 groups (P>0. 05). Plasma and renal tissue ouabain levels, plasma renin activity, angiotensin Ⅱ and aldosterone contents in ouabain-hypertensive rats were

  7. Assessing plasma lipid levels, body weight, and hepatic and renal toxicity following chronic oral administration of a water soluble phytostanol compound, FM-VP4, to gerbils.

    Science.gov (United States)

    Wasan, K M; Najafi, S; Wong, J; Kwong, M; Pritchard, P H

    2001-01-01

    to controls. A significant increase in HDL cholesterol concentrations was observed in gerbils administered 2% FM-VP4 in their diet and 4% FM-VP4 in their drinking water compared to controls. No significant elevations in AST, ALT and creatinine concentrations were reported for all treatment groups compared to controls. These findings suggest that FM-VP4 significantly decrease plasma lipids and body weight with no apparent hepatic or renal toxicity.

  8. Litholytic property of Kulattha (Dolichous biflorus) vs potassium citrate in renal calculus disease: a comparative study.

    Science.gov (United States)

    Singh, Rana Gopal; Behura, Sanjeev Kumar; Kumar, Rakesh

    2010-05-01

    Renal calculus disease is associated with recurrence after its surgical removal in large number of cases. Kulattha is acclaimed to have litholytic property in ayurvedic literature. We decided to compare the litholytic property of Kulattha with potassium citrate, an agent used to reduce stone recurrence in modern medicine. Forty seven patients with diagnosis of calcium oxalate renal calculi were taken in study. Twenty four patients received Kulattha (Group I) and 23 patients were given potassium citrate(Group II) for a period of 6 months. The size of renal calculi was studied by periodic ultrasound assessment in both groups. Mean size of stone in group I at 0 month and at 6 month were 5.42 +/- 1.55 mm and 4.26 +/- 1.2 mm. mean size of stone in group II at 0 month and at 6 month was 6.46 +/- 3.08 mm and 4.64 +/- 1.40 mm. Statistical analysis showed that P value of less than 0.05 was seen in the first group from 0 to 6 month. There was no significant difference in the stone size within group II when the 3rd month and 6th month visit was compared with initial visit. Kulattha can be used to reduce the recurrence of calcium oxalate stone and it is shown to have a better result than the use of conventional potassium citrate in such patients.

  9. COMPARATIVE STUDY OF THYROID ABNORMALITIES WITH SEVERITY OF CHRONIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    Mohammed

    2015-10-01

    Full Text Available BACKGROUND: Patients with CRF often have signs & symptoms suggestive of thyroid dysfunctions. Prevalence of hypothyroidism in patients with terminal renal failure is 5%, in comparison with that in hospitalized patients with normal renal function . CKD is associated with higher prevalence of hypothyroidism, both overt and subclinical, but not with hyperthyroidism. In fact, the prevalence of primary hypothyroidism is mainly in the subclinical form, which increases as GFR decreases. OBJECTIVES: To estimate thyroid hormone levels i. e. T 3 , T 4 & TSH in CRF. To estimate Serum urea & creatinine for selection and categorizing the study subjects in to different grades of CRF. To study the thyroid hormone levels and thyroid abnormalities as the severity of CRF increases. MATERIALS AND METHO DS: In this study 30 male patients of aged between 40 - 70yrs . with serum creatinine >5.5mg/dl & urea >55mg/dl and dipstick test positive for protein with symptoms of chronic renal failure are taken as cases. Age and sex matched normal healthy indi vi duals ar e taken as controls. Serum Urea Estimated by DAM Method, serum creatinine is estimated by Jaffe’s method and Serum levels of T 3 , T 4 & TSH were analysed by using CLIA method. Results: T 3 , T 4 decreases and TSH increases significantly in cases compare to the controls as the severity of dieses increases . In our study 10% of patients of CRF are hypothyroid and all these hypothyroid patients belongs to serum creatinine above 6 mg/dl category. CONC LUSION: Mean of T 3 , T 4 decreases TSH increases significantly in cases compare to controls as the severity of CRF increases. The risk of hypothyroidism in chronic renal failure is very high if serum creatinine level are above 6 mg/dl.

  10. Comparative toxicant sensitivity of sexual and asexual reproduction in the rotifer Brachionus calyciflorus

    Energy Technology Data Exchange (ETDEWEB)

    Snell, T.W. [Georgia Inst. of Tech., Atlanta, GA (United States). School of Biology; Carmona, M.J. [Univ. de Valencia (Spain). Area de Ecologia

    1995-03-01

    Cyclically parthenogenetic zooplankters like rotifers are important tools for assessing toxicity in aquatic environments. Sexual reproduction is an essential component of rotifer life cycles, but current toxicity tests utilize only asexual reproduction. The authors compared the effects of four toxicants on asexual and sexual reproduction of the rotifer Brachionus calyciflorus. Toxicants had a differential effect on sexual and asexual reproduction, with sexual reproduction consistently the most sensitive. Concentrations of 0.2 {mu}g/ml PCP (sodium pentachlorophenate) had no effect on the asexual reproductive rate, but significantly reduced sexual reproduction. Likewise, chlorpyrifos concentrations of 0.3 {mu}g/ml had no significant effect on asexual reproduction, but sexual reproduction was significantly reduced. There was no difference in NOECs, LOECs, and chronic values for asexual and sexual reproduction for cadmium and naphthol tests. However, comparison of toxicant effect levels revealed that sexual reproduction was more strongly reduced at each toxicant concentration. The four toxicants tested inhibited sexual reproduction 2 to 68 times more than asexual reproduction at the lowest observed effect concentrations. Toxicants inhibited sexual reproduction in its initial step: sexual female production. Because sexual reproduction is more sensitive, toxicity tests based exclusively on asexual reproduction may not be protective of rotifer life cycles.

  11. Comparative toxicity of water soluble fractions of four oils on the growth of a Microalga

    Digital Repository Service at National Institute of Oceanography (India)

    Phatarpekar, P.V.; Ansari, Z.A.

    Toxic effects of water soluble fractions (WSF) of four different fuel oils on a microalga. Tetraselmis gracilis, were examined and compared. On applying different concentrations of WSF, a decrease in cell population was observed. Depending...

  12. Assessment of Metal Toxicity in Marine Ecosystems: Comparative Toxicity Potentials for Nine Cationic Metals in Coastal Seawater.

    Science.gov (United States)

    Dong, Yan; Rosenbaum, Ralph K; Hauschild, Michael Z

    2016-01-05

    This study is a first attempt to develop globally applicable and spatially differentiated marine comparative toxicity potentials (CTPs) or ecotoxicity characterization factors for metals in coastal seawater for use in life cycle assessment. The toxicity potentials are based exclusively on marine ecotoxicity data and take account of metal speciation and bioavailability. CTPs were developed for nine cationic metals (Cd, Cr(III), Co, Cu(II), Fe(III), Mn, Ni, Pb, and Zn) in 64 large marine ecosystems (LMEs) covering all coastal waters in the world. The results showed that the CTP of a specific metal varies 3-4 orders of magnitude across LMEs, largely due to different seawater residence times. Therefore, the highest toxicity potential for metals was found in the LMEs with the longest seawater residence times. Across metals, the highest CTPs were observed for Cd, Pb, and Zn. At the concentration levels occurring in coastal seawaters, Fe acts not as a toxic agent but as an essential nutrient and thus has CTPs of zero.

  13. Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity.

    Science.gov (United States)

    Koh, Y V; Tang, J I; Choo, B A; Koh, M S; Lee, K M

    2014-01-01

    The addition of pelvic radiotherapy to brachytherapy (EBRT-BT) in early-stage endometrial cancer is controversial and may cause unnecessary toxicity. The incidence of acute toxicity of EBRT-BT will have an impact on clinical decision and patient compliance but is currently poorly understood. This study compares the acute toxicities of EBRT-BT versus BT alone. Seventy-nine patients with FIGO Stage IA-II endometrial cancer who underwent adjuvant radiotherapy, (EBRT-BT or BT alone) from 2001 to 2011 were included in the study. Medical records of these patients were reviewed retrospectively and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients were followed up for at least three months post-treatment to assess resolution of toxicity. The mean age of the study group was 60.6 years. Median follow-up was four years. Forty patients received EBRT-BT. There was a 37% increase in Grade 1-3 diarrhea with the addition of pelvic radiotherapy (OR 18.67, p < 0.0005) and a 34% increase in lethargy (p < 0.0005). There was also an increased occurrence of genitourinary and skin toxicities. Two patients in the EBRT-BT group required hospitalisation for severe diarrhea and three patients were unable to complete the treatment. All acute toxicities had resolved by three months post treatment. EBRT-BT causes significantly more acute toxicities compared to BT alone. Patients should be informed of this during counselling.

  14. Comparative and combined acute toxicity of butachlor, imidacloprid and chlorpyrifos on earthworm, Eisenia fetida.

    Science.gov (United States)

    Chen, Chen; Wang, Yanhua; Zhao, Xueping; Wang, Qiang; Qian, Yongzhong

    2014-04-01

    Various pesticides have become widespread contaminants of soils due to their large applications in agriculture and homes. An earthworm assay was used to assess the acute toxicity of butachlor, imidacloprid and chlorpyrifos with different modes of action. Ecotoxicities of these pesticides were compared for earthworm Eisenia fetida separately and in combination in artificial soil and contact filter paper tests. Imidacloprid was the most toxic for E. fetida with LC₅₀ (lethal concentration 50) values three orders magnitude lower than that of butachlor and chlorpyrifos in both tests. The toxicity of the mixtures was compared to that predicted by the concentration addition (CA) model. According to the CA model, the observed toxicities of all binary mixtures were less than additive. However, for all the mixtures in 14 d artificial soil test, and mixtures of butachlor plus chlorpyrifos and imidacloprid plus chlorpyrifos in 48 h contact filter paper test, the difference in toxicity was less than 30%, hence it was concluded that the mixtures conformed to CA. The combined effects of the pesticides in contact filter paper tests were not consistent with the results in artificial soil toxicity tests, which may be associated with the interaction of soil salts with the pesticides. The CA model provides estimates of mixture toxicity that did not markedly underestimate the measured toxicity, and therefore the CA model is the most suitable to use in ecological risk assessments of the pesticides.

  15. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: kidney effects.

    Science.gov (United States)

    Yoo, Hong Sik; Bradford, Blair U; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B; Bodnar, Wanda M; Ball, Louise M; Gold, Avram; Rusyn, Ivan

    2015-01-01

    Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal-cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, interspecies and interindividual differences, and the mode of action for kidney carcinogenicity. It was postulated that TCE renal metabolite levels are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in subacute (600 mg/kg/d; 5 d; 7 inbred mouse strains) and subchronic (100 or 400 mg/kg/d; 1, 2, or 4 wk; 2 inbred mouse strains) designs. The quantitative relationship was evaluated between strain-, dose, and time-dependent formation of TCE metabolites from cytochrome P-450-mediated oxidation (trichloroacetic acid [TCA], dichloroacetic acid [DCA], and trichloroethanol) and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In subacute study, interstrain differences in renal TCE metabolite levels were observed. In addition, data showed that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In subchronic study, peroxisome proliferator-marker gene induction and renal toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ but not C57BL/6J mice. Overall, data demonstrated that renal TCE metabolite levels are associated with kidney-specific toxicity and that these effects are strain dependent.

  16. Prospective Randomized Trial Comparing Hepatic Venous Outflow and Renal Function after Conventional versus Piggyback Liver Transplantation.

    Directory of Open Access Journals (Sweden)

    Marília D'Elboux Guimarães Brescia

    Full Text Available This randomized prospective clinical trial compared the hepatic venous outflow drainage and renal function after conventional with venovenous bypass (n = 15 or piggyback (n = 17 liver transplantation.Free hepatic vein pressure (FHVP and central venous pressure (CVP measurements were performed after graft reperfusion. Postoperative serum creatinine (Cr was measured daily on the first week and on the 14th, 21st and 28th postoperative days (PO. The prevalence of acute renal failure (ARF up to the 28th PO was analyzed by RIFLE-AKIN criteria. A Generalized Estimating Equation (GEE approach was used for comparison of longitudinal measurements of renal function.FHVP-CVP gradient > 3 mm Hg was observed in 26.7% (4/15 of the patients in the conventional group and in 17.6% (3/17 in the piggyback group (p = 0.68. Median FHVP-CVP gradient was 2 mm Hg (0-8 mmHg vs. 3 mm Hg (0-7 mm Hg in conventional and piggyback groups, respectively (p = 0.73. There is no statistically significant difference between the conventional (1/15 and the piggyback (2/17 groups regarding massive ascites development (p = 1.00. GEE estimated marginal mean for Cr was significantly higher in conventional than in piggyback group (2.14 ± 0.26 vs. 1.47 ± 0.15 mg/dL; p = 0.02. The conventional method presented a higher prevalence of severe ARF during the first 28 PO days (OR = 3.207; 95% CI, 1.010 to 10.179; p = 0.048.Patients submitted to liver transplantation using conventional or piggyback methods present similar results regarding venous outflow drainage of the graft. Conventional with venovenous bypass technique significantly increases the harm of postoperative renal dysfunction.ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01707810.

  17. Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

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    Liye Zhu

    2016-12-01

    Full Text Available Ochratoxin A (OTA displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD and livers (SOD and GSH. DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model.

  18. Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

    Science.gov (United States)

    Zhu, Liye; Yu, Tao; Qi, Xiaozhe; Gao, Jing; Huang, Kunlun; He, Xiaoyun; Luo, Haoshu; Xu, Wentao

    2016-01-01

    Ochratoxin A (OTA) displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD) and livers (SOD and GSH). DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model. PMID:27983637

  19. Hydrogen sulfide: A novel nephroprotectant against cisplatin-induced renal toxicity.

    Science.gov (United States)

    Dugbartey, George J; Bouma, Hjalmar R; Lobb, Ian; Sener, Alp

    2016-07-01

    Cisplatin is a potent chemotherapeutic agent for the treatment of various solid-organ cancers. However, a plethora of evidence indicates that nephrotoxicity is a major side effect of cisplatin therapy. While the antineoplastic action of cisplatin is due to formation of cisplatin-DNA cross-links, which damage rapidly dividing cancer cells upon binding to DNA, its nephrotoxic effect results from metabolic conversion of cisplatin into a nephrotoxin and production of reactive oxygen species, causing oxidative stress leading to renal tissue injury and potentially, kidney failure. Despite therapeutic targets in several pre-clinical and clinical studies, there is still incomplete protection against cisplatin-induced nephrotoxicity. Hydrogen sulfide (H2S), the third discovered gasotransmitter next to nitric oxide and carbon monoxide, has recently been identified in several in vitro and in vivo studies to possess specific antioxidant, anti-inflammatory and anti-apoptotic properties that modulate several pathogenic pathways involved in cisplatin-induced nephrotoxicity. The current article reviews the molecular mechanisms underlying cisplatin-induced nephrotoxicity and displays recent findings in the H2S field that could disrupt such mechanisms to ameliorate cisplatin-induced renal injury.

  20. Comparative in-vivo toxicity of venoms from South Asian hump-nosed pit vipers (Viperidae: Crotalinae: Hypnale

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    Silva Anjana

    2012-08-01

    Full Text Available Abstract Background Envenoming by south Asian hump-nosed pit vipers (Genus: Hypnale is a significant health issue in Sri Lanka and in peninsular India. Bites by these snakes frequently lead to local envenoming, coagulopathy and acute renal failure even resulting in death. Recently the genus was revised and the existence of three species viz H. hypnale, H. nepa and H. zara were recognized. There is, however, a paucity of information on the toxicity of the venoms of these species. Hence, we compared the toxic effects of the three Hypnale venoms using BALB/c mice. Findings Intraperitoneal median lethal doses (LD50 for H. hypnale, H. zara and H. nepa venoms were 1.6, 6.0 and 9.5 μg protein/g respectively. Minimum haemorrhagic doses for venoms of H. hypnale, H. zara and H. nepa were 3.4, 11.0 and 16.6 μg protein/mouse respectively. The minimum necrotic doses for the same venoms were 15.0, 55.1 and 68.2 μg protein/mouse respectively. Severe congestion and petecheal haemorrhages were observed in lungs, kidneys, liver and the alimentary tract. Histopathogical examination of kidneys revealed proximal tubular cell injury and acute tubular necrosis with intact basement membrane indicating possible direct nephrotoxicity. Hypnale venoms caused pulmonary oedema, hepatocellular degeneration and necrosis, focal neuronal degeneration in brain and extramedullary haemopoiesis in spleen. H. hypnale venom caused all above histopathological alterations at lower doses compared to the other two. Conclusion Hypnale venoms cause similar pathological changes with marked differences in the severity of the toxic effects in vivo. Therefore, differences in the severity of the clinical manifestations could possibly be seen among bite victims of the three Hypnale species.

  1. Encephalopathy and Hypotonia due to Baclofen Toxicity in a Patient with End-Stage Renal Disease

    OpenAIRE

    Ijaz, Mohsin; Tariq, Hassan; KASHIF,MUHAMMAD; Marquez, Jose Gomez

    2015-01-01

    Patient: Female, 57 Final Diagnosis: Baclofen toxicity Symptoms: Encephalopathy • hypotonia Medication: Baclofen Clinical Procedure: Hemodialysis Specialty: Critical Care Objective: Unusual or unexpected effect of treatment Background: Baclofen is a centrally acting gamma-aminobutyric acid agonist used for the symptomatic relief of skeletal muscle spasm and spasticity in traumatic spinal cord lesions, multiple sclerosis, cerebral palsy, and stroke. It is also used in the treatment of chronic ...

  2. A Case of Sodium Chlorite Toxicity Managed with Concurrent Renal Replacement Therapy and Red Cell Exchange

    OpenAIRE

    Romanovsky, Adam; Djogovic, Dennis; Chin, Dat

    2012-01-01

    Introduction Sodium chlorite is a powerful oxidizing agent with multiple commercial applications. We report the presentation and management of a single case of human toxicity of sodium chlorite. Case report A 65-year-old man presented to hospital after accidentally ingesting a small amount of a sodium chlorite solution. His principal manifestations were mild methemoglobinemia, severe oxidative hemolysis, disseminated intravascular coagulation, and anuric acute kidney injury. He was managed wi...

  3. Protective Effects of Zinc Supplementation on Renal Toxicity in Rats Exposed to Cadmium

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    Morshedi

    2014-07-01

    Full Text Available Background Cadmium (Cd is a nonessential element with many industrial applications and is one of the most toxic pollutants in the environment. The ultimate goal of occupational health is prevention of health hazards on workplace; hence, is as a hazardous chemical contaminant in the workplace, Cd needs special attention. Objectives The object of this study was to determine the effect of ZnCl2 on Cd-induced nephrotoxicity in rats. Materials and Methods Adult male rats were given CdCl2 at doses of 0, 1, 2, and 3 mg/kg. Another series of rats were pretreated with 4 mg/kg of ZnCl2 30 minutes prior to administration of various doses of CdCl2. The experiment was repeated for seven consecutive days. Twenty-four hours after administering the latest dose, animals were sacrificed. Blood samples were analyzed for blood urea nitrogen (BUN and creatinine levels. Kidney tissues were excised for measuring malondialdehyde (MDA concentration. Results In contrast to the animals that received ZnCl2, CdCl2 induced a dose-dependent elevation in BUN, creatinine, and MDA in those without ZnCl2 pretreatment. Zinc chloride had significantly decreased all biochemical parameters and protected kidney cells against Cd-induced toxicity. Conclusions The results of this study supported the potential protective effects of ZnCl2 on rat kidney tissues against CdCl2 toxicity.

  4. Renal function parameters of Thai vegans compared with non-vegans.

    Science.gov (United States)

    Wiwanitkit, Viroj

    2007-01-01

    In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p vegans and controls. Vegans had significantly lower urine protein level.

  5. Greater Sensitivity of Blood Pressure Than Renal Toxicity to Tyrosine Kinase Receptor Inhibition With Sunitinib

    DEFF Research Database (Denmark)

    Lankhorst, Stephanie; Baelde, Hans J; Kappers, Mariëtte H W

    2015-01-01

    of these side effects. Normotensive Wistar Kyoto rats were exposed to 3 different doses of sunitinib or vehicle. After 8 days, rats were euthanized. Telemetrically measured blood pressure rose dose dependently, from 13 to 30 mm Hg. Proteinuria was present at all doses, but a rise in cystatin C occurred only...... histological abnormalities with the low dose. Podocyte number per glomerular circumference did not change. Glomerular nephrin, Neph1, podocin, and endothelin-converting enzyme gene expression were downregulated in a dose-dependent manner. We conclude that the sunitinib-induced rise in blood pressure requires......Hypertension and renal injury are off-target effects of sunitinib, a tyrosine kinase receptor inhibitor used for the treatment of various tumor types. Importantly, these untoward effects are accompanied by activation of the endothelin system. Here, we set up a study to explore the dose dependency...

  6. A study of Semen Strychni-induced renal injury and herb-herb interaction of Radix Glycyrrhizae extract and/or Rhizoma Ligustici extract on the comparative toxicokinetics of strychnine and brucine in rats.

    Science.gov (United States)

    Gu, Liqiang; Wang, Xiaofan; Liu, Zhenzhen; Ju, Ping; Zhang, Lunhui; Zhang, Yuanyuan; Ma, Bingjie; Bi, Kaishun; Chen, Xiaohui

    2014-06-01

    Recently, the renal injury caused by Semen strychni and its major toxic constituents, strychnine and brucine, was reported in many clinical cases. Hence, this study was conducted to investigate the renal injury induced by Semen Strychni and the protective effects of Radix Glycyrrhizae and Rhizoma Ligustici. The protective mechanisms were related to the comparative toxicokinetics of strychnine and brucine. Serum and urine uric acid and creatinine were used as renal function markers to evaluate the condition of kidney, and renal injury was directly reflected by histopathological changes. Compared with rats in blank group and protective herb groups, rats in Semen Strychni high-dose group showed significant differences in the results of renal function markers, and various glomerular and tubular degenerations were found in the histopathological study. The decreased AUC (only strychnine) and Cmax, the increased Tmax by Radix Glycyrrhizae and the decreased T1/2 by Radix Glycyrrhizae and Rhizoma Ligustici were found in model groups. Results indicated that high dose of Semen Strychni might induce renal injury. Radix Glycyrrhizae and Rhizoma Ligustici might work together and have effects on the elimination of strychnine and brucine. The protective effects of Radix Glycyrrhizae might also be explained by the slow absorption of the alkaloids. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

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    Boczkowski Jorge

    2009-04-01

    Full Text Available Abstract Background A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red and analyzed 2 time points (3 and 24 hours for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality was calculated. Results The use of MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive experimental design to assess the cytotoxic effect of one nanoparticle. With this experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate toxicity, and no toxicity was observed for Tungsten Carbide. No correlation between cytotoxicity and equivalent spherical diameter or specific surface area was found. Conclusion Our study clearly highlights the difference of sensitivity between cell types and cytotoxicity assays that has to be carefully taken into account when assessing nanoparticles toxicity.

  8. Comparative study of impact of hemodialysis and renal transplantation on cognitive functions in ESRD patients.

    Science.gov (United States)

    Anwar, Waleed; Ezzat, Haitham; Mohab, Amr

    2015-01-01

    Cognitive impairment is defined as a newly appeared deficit in at least two areas of cognitive functions, including disturbances in memory, executive functioning, attention or speed of information processing, perceptual motor abilities, or language. Cognitive impairment is highly prevalent in ESRD patients when compared with the general population. It has also been associated with a decreased quality of life. Cognitive functions in patients with ESRD showed improvement with dialysis and renal transplantation. These findings illustrate the potential importance of evaluating and comparing the effects of hemodialysis and transplantation regarding cognitive performance and thus quality of life in ESRD patients and normal subjects. This study was carried out in 100 patients (50 ESRD patients on regular hemodialysis for at least 6 months and 50 post-transplant patients who had maintained successful kidney graft for at least 3 months). All patients underwent laboratory and psychometric scoring tests, including trail making test part A, trail making test part B, digit span, and mini-mental state examination. Thirty healthy adults matched by age and sex served as a control group. The results showed significant differences in cognitive function tests results between transplant and hemodialysis patients (P0.05). Renal transplantation as a modality of treatment, in ESRD patients, is superior to hemodialysis in terms of cognitive performance improvement. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Comparative Toxicity of Different Crude Oils on the Cardiac Function of Marine Medaka (Oryzias melastigma Embryo

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    Zhendong Zhang

    2014-12-01

    Full Text Available The acute toxic effect of different crude oils (heavy crude oil and bonny light crude oil on embryos of marine medaka Oryzias melastigma was measured and evaluated by exposure to the water-accommodated fraction (WAF in the present study. The cardiac function of medaka embryos was used as target organ of ecotoxicological effect induced by oil exposure. Results showed that the developing marine medaka heart was a sensitive target organ to crude oil exposure the heavy crude oil WAF was more toxic to cardiac function of medaka embryos than bonny light cured oil one. Cardiac function of medaka embryos was clearly affected by exposure to heavy crude oil WAF after 24 hours exposure and showed a dose-dependent slowing of heart rate. Furthermore, swelled and enlarged heart morphology, lowered blood circulation and accumulation of blood cells around the heart area were found. However, the toxic effect of bonny light crude oil on cardiac function of medaka embryos was comparatively low. Statistical results showed that the cardiac function was only affected by highest bonny light crude oil WAF (9.8 mg/L exposure treatment. These findings indicated that cardiac function of marine medaka embryo was a good toxicity model for oil pollution and could be used to compare and evaluate the toxicity of different crude oils. The heart rate was an appropriate endpoint in the acute toxicity test.

  10. Comparative use of bacterial, algal and protozoan tests to study toxicity of azo- and anthraquinone dyes.

    Science.gov (United States)

    Novotný, Cenek; Dias, Nicolina; Kapanen, Anu; Malachová, Katerina; Vándrovcová, Marta; Itävaara, Merja; Lima, Nelson

    2006-06-01

    Toxicity of two azo dyes (Reactive Orange 16 (RO16); Congo Red (CR)) and two anthraquinone dyes (Remazol Brilliant Blue R (RBBR); Disperse Blue 3 (DB3)) were compared using bacterium Vibrio fischeri, microalga Selenastrum capricornutum and ciliate Tetrahymena pyriformis. The following respective endpoints were involved: acute toxicity measured as bacterial luminescence inhibition, algal growth inhibition, and the effects on the protozoa including viability, growth inhibition, grazing effect and morphometric effects. In addition, mutagenicity of the dyes was determined using Ames test with bacterium Salmonella typhimurium His(-). DB3 dye was the most toxic of all dyes in the bacterial, algal and protozoan tests. In contrast to other dyes, DB3 exhibited mutagenic effects after metabolic activation in vitro in all S. typhimurium strains used. Of the methods applied, the algal test was the most sensitive to evaluate toxicity of the dyes tested.

  11. Comparative toxicity study of Ag, Au, and Ag-Au bimetallic nanoparticles on Daphnia magna.

    Science.gov (United States)

    Li, Ting; Albee, Brian; Alemayehu, Matti; Diaz, Rocio; Ingham, Leigha; Kamal, Shawn; Rodriguez, Maritza; Bishnoi, Sandra Whaley

    2010-09-01

    A comparative assessment of the 48-h acute toxicity of aqueous nanoparticles synthesized using the same methodology, including Au, Ag, and Ag-Au bimetallic nanoparticles, was conducted to determine their ecological effect in freshwater environments through the use of Daphnia magna, using their mortality as a toxicological endpoint. D. magna are one of the standard organisms used for ecotoxicity studies due to their sensitivity to chemical toxicants. Particle suspensions used in toxicity testing were well-characterized through a combination of absorbance measurements, atomic force or electron microscopy, flame atomic absorption spectrometry, and dynamic light scattering to determine composition, aggregation state, and particle size. The toxicity of all nanoparticles tested was found to be dose and composition dependent. The concentration of Au nanoparticles that killed 50% of the test organisms (LC(50)) ranged from 65-75 mg/L. In addition, three different sized Ag nanoparticles (diameters = 36, 52, and 66 nm) were studied to analyze the toxicological effects of particle size on D. magna; however, it was found that toxicity was not a function of size and ranged from 3-4 μg/L for all three sets of Ag nanoparticles tested. This was possibly due to the large degree of aggregation when these nanoparticles were suspended in standard synthetic freshwater. Moreover, the LC(50) values for Ag-Au bimetallic nanoparticles were found to be between that of Ag and Au but much closer to that of Ag. The bimetallic particles containing 80% Ag and 20% Au were found to have a significantly lower toxicity to Daphnia (LC(50) of 15 μg/L) compared to Ag nanoparticles, while the toxicity of the nanoparticles containing 20% Ag and 80% Au was greater than expected at 12 μg/L. The comparison results confirm that Ag nanoparticles were much more toxic than Au nanoparticles, and that the introduction of gold into silver nanoparticles may lower their environmental impact by lowering the amount

  12. Complete remission with sunitinib in a poor-risk patient with metastatic renal cell carcinoma: the fine balance between toxicity and efficacy.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Bimbatti, Davide; Fantinel, Emanuela; Modena, Alessandra; Simbolo, Michele; Brunelli, Matteo; Artibani, Walter; Martignoni, Guido; Scarpa, Aldo; Tortora, Giampaolo

    2015-04-01

    Sunitinib represents a reasonable therapeutic option for first-line treatment of poor-risk metastatic renal cell carcinoma and the treatment should aim at the delicate balance between managing side effects to improve the toxicity profile and patient compliance to treatment while maintaining anticancer efficacy. Achievement of a complete response, although rare, is possible, even in poor-risk patients. Treatment discontinuation represents a viable alternative for both tumour biology and patients' quality of life. To date, no molecular markers have been identified with prognostic and/or predictive value for guiding therapeutic decisions. Further research should aim at gaining in-depth knowledge of renal cell carcinoma biology for a tailored personalized therapy. We report a case of poor-risk metastatic renal cell carcinoma, with Von Hippel-Lindau loss of function, which achieved and maintained a complete remission after first-line therapy with sunitinib by using a reduced dosage and a modified schedule of treatment.

  13. Hypercalcemia and renal function impairment associated with vitamin D toxicity: case report

    Directory of Open Access Journals (Sweden)

    Vanessa Guerra

    Full Text Available Abstract Nowadays vitamin D (25-OHD deficiency is supposed to be a global epidemic condition. Expectedly, vitamin D measurement and intake exponentially increased in Brazil in this decade. Although the benefit of vitamin D to general health is still in debate, its indiscriminate use potentially may lead to enhance the incidence of vitamin D intoxication, which is considered a rare disorder. We report a case of a 70 year old diabetic male with chronic renal disease (blood creatinine of 1.6 mg/dL who progressed suddenly to acute kidney injury (blood creatinine of 5.7 mg/dL associated with hypercalcemia and high blood levels of vitamin D. Vitamin D and calcitriol were discontinued and hypercalcemia was managed by hydration followed by furosemide. Thereafter, disodium pamidronate was administered and the patient did not undergo on dialysis. It took approximately 14 months to normalize 25-OHD levels and blood creatinine returned to basal levels only after 24 months. The indicated labeling dosage was 2000 IU, but most likely the vitamin D manipulated preparation was higher as the vitamin D blood levels were very high. Although rare, vitamin D intoxication is becoming more frequent as the patients use frequently manipulated preparations that could be subject to errors in the manufacturing and labeling of the tablets or capsules. The present report alerts to the potential increase in the incidence of severe vitamin D intoxication due to the frequent use of this secosteroid as a nutritional supplement. At the same time, it is necessary to improve regulation on the nutrient supplement market.

  14. Hypercalcemia and renal function impairment associated with vitamin D toxicity: case report.

    Science.gov (United States)

    Guerra, Vanessa; Vieira Neto, Osvaldo Merege; Laurindo, Alan Fernandes; Paula, Francisco Jose Albuquerque de; Moysés Neto, Miguel

    2016-12-01

    Nowadays vitamin D (25-OHD) deficiency is supposed to be a global epidemic condition. Expectedly, vitamin D measurement and intake exponentially increased in Brazil in this decade. Although the benefit of vitamin D to general health is still in debate, its indiscriminate use potentially may lead to enhance the incidence of vitamin D intoxication, which is considered a rare disorder. We report a case of a 70 year old diabetic male with chronic renal disease (blood creatinine of 1.6 mg/dL) who progressed suddenly to acute kidney injury (blood creatinine of 5.7 mg/dL) associated with hypercalcemia and high blood levels of vitamin D. Vitamin D and calcitriol were discontinued and hypercalcemia was managed by hydration followed by furosemide. Thereafter, disodium pamidronate was administered and the patient did not undergo on dialysis. It took approximately 14 months to normalize 25-OHD levels and blood creatinine returned to basal levels only after 24 months. The indicated labeling dosage was 2000 IU, but most likely the vitamin D manipulated preparation was higher as the vitamin D blood levels were very high. Although rare, vitamin D intoxication is becoming more frequent as the patients use frequently manipulated preparations that could be subject to errors in the manufacturing and labeling of the tablets or capsules. The present report alerts to the potential increase in the incidence of severe vitamin D intoxication due to the frequent use of this secosteroid as a nutritional supplement. At the same time, it is necessary to improve regulation on the nutrient supplement market.

  15. Comparative QSAR studies on toxicity of phenol derivatives using quantum topological molecular similarity indices.

    Science.gov (United States)

    Hemmateenejad, Bahram; Mehdipour, Ahmad R; Miri, Ramin; Shamsipur, Mojtaba

    2010-05-01

    Quantitative structure activity relationship (QSAR) analyses using a novel type of electronic descriptors called quantum topological molecular similarity (QTMS) indices were operated to describe and compare the mechanisms of toxicity of phenols toward five different strains (i.e., Tetrahymena pyriformis, L1210 Leukemia, Pseudomonas putida, Raja japonica and Cucumis sativus). The appropriate QSAR models for the toxicity data were obtained separately employing partial least squares (PLS) regression combined with genetic algorithms (GA), as a variable selection method. The resulting QSAR models were used to identify molecular fragments of phenol derivatives whose electronic properties contribute significantly to the observed toxicities. Using this information, it was feasible to discriminate between the mechanisms of action of phenol toxicity to the studied strains. It was found that toxicities of phenols to all strains, except with L1210 Leukemia, are significantly affected by electronic features of the phenolic hydroxyl group (C-O-H). Meanwhile, the resulting models can describe the inductive and resonance effects of substituents on various toxicities.

  16. Comparative toxicity of the pesticides carbofuran and malathion to the freshwater flagellate Euglena gracilis.

    Science.gov (United States)

    Azizullah, Azizullah; Richter, Peter; Häder, Donat-Peter

    2011-08-01

    Pesticides are toxic chemicals used for agricultural as well as non-agricultural purposes. The toxicity of pesticides does not remain limited to the site of application but they also cause toxicity to non-target organisms in terrestrial as well as in aquatic environments. This study discusses the comparative toxicity of a carbamate (carbofuran) and an organophosphorus (malathion) pesticide to the freshwater flagellate Euglena gracilis during short- and long-term exposures. To evaluate the toxicity of the pesticides, different parameters of the flagellate, like cell density, motility, swimming velocity, cell shape, gravitactic orientation, photosynthetic efficiency, and concentration of light harvesting pigments, were used as end points. Carbofuran was found to be more toxic to E. gracilis than malathion and adversely affected almost all the tested parameters in short- and long-term experiments. The only significant adverse effect by malathion could be demonstrated on the swimming velocity of cells in short-term experiments. The adverse effects of the pesticides were more pronounced during short-term than during long-term exposure.

  17. A clinical comparative study of the management of chronic renal failure with Punarnavadi compound.

    Science.gov (United States)

    Prashanth, G S; Baghel, M S; Ravishankar, B; Gupta, S N; Mehta, Miten P

    2010-04-01

    India like any other country is facing a silent epidemic of chronic renal failure (CRF)- a facet of the health transition associated with industrialization partly fuelled by increase in sedentary lifestyle, low birth weight and malnutrition. Increasing figures by many folds seen is posing a difficult situation to overcome with respect to economy and health of the working and earning population of the nation. There is an urgent need to explore, highlight new interventions and modify modifiable risk factors as a basis for treatment strategies to prevent the development and progression of CRF. The present study was taken up to evaluate the role of trial formulation tab. Punarnavadi compound in the management of chronic renal failure. This was an open clinical comparative study in controlled circumstances wherein 67 patients were studied for two months in three groups- Group A (allopathic control), Group B (ayurvedic control) and Group C (ayurvedic test). It was a multi-centric study; patients were registered from Anandababa charitable dialysis centre, Jamnagar, Kayachikitsa O.P.D. of I.P.G.T. and R.A. Jamnagar and P. D. Patel Ayurveda hospital, Nadiad. Results were assessed on 15 parameters using Students (paired) 't' test. Group A patients showed comparatively better results in eight parameters- weight, platelet count, serum urea, serum uric acid, serum sodium, potassium, chloride and total proteins. Parameter Hemoglobin% showed better results in Group B patients and in Group C patients comparatively better results in six parameters viz.- quality of life (breathlessness, weakness, general functional capacity), total count, serum creatinine and serum calcium - were observed. Throughout the study, trial drug tab. Punarnavadi compound did not show any adverse drug reaction. The results of this study will help in developing a cheap and safe treatment for the management of CRF.

  18. Comparative study of anticoagulation versus saline flushes in continuous renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Nagarik Amit

    2010-01-01

    Full Text Available Systemic heparinization during continuous renal replacement therapy (CRRT is associated with disadvantage of risk of bleeding. This study analyses the efficacy of frequent saline flushes compared with heparin anticoagulation to maintain filter life. From January 2004 to November 2007, 65 critically ill patients with acute renal failure underwent CRRT. Continuous venovenous hemodialfiltration (CVVHDF was performed using Diapact Braun CRRT machine. 1.7% P.D. fluid was used as dialysate. 0.9% NS with addition of 10% Ca Gluconate, Magnesium Sulphate, Soda bicarbonate and Potassium Chloride added sequentially in separate units were used for replacement, carefully monitoring their levels. Anticoagulation of extracorporeal circuit was achieved with unfractionated heparin (250-500 units alternate hour in 35 patients targeting aPTT of 45-55 seconds. No anticoagulation was used in 30 patients with baseline APTT > 55 seconds and extracorporeal circuit was maintained with saline flushes at 30 min interval. 65 pa-tients including 42 males. Co-morbidities were comparable in both groups. HMARF was signifi-cantly more common in heparin group while Sepsis was comparable in both the groups. CRRT parameters were similar in both groups. Average filter life in heparin group was 26 ± 6.4 hours while it was 24.5 ± 6.36 hours in heparin free group ( P=NS. Patients receiving heparin had 16 bleeding episodes (0.45/patient while only four bleeding episodes occurred in heparin free group (0.13/patient, P< 0.05. Mortality was 71% in heparin group and 67% in heparin free group. Frequent saline flushes is an effective mode of maintainance of extracorporeal circuit in CRRT when aPTT is already on the higher side, with significantly decreased bleeding episodes.

  19. Comparative Toxicity of Soy Biodiesel and Diesel Emissions in Healthy and Allergic Mice

    Science.gov (United States)

    Toxicity from combustion of 100% soy-based biodiesel (B100) was compared to that of petrodiesel (B0) or a 20% biodiesel / 80% petrodiesel mix (B20) in healthy and house dust mite (HDM)-allergic Balb/cJ mice. Exhaust from combustion of B0, B20, or B100 was diluted to target conce...

  20. Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

    Science.gov (United States)

    Kaymakcalan, Marina D; Xie, Wanling; Albiges, Laurence; North, Scott A; Kollmannsberger, Christian K; Smoragiewicz, Martin; Kroeger, Nils; Wells, J Connor; Rha, Sun-Young; Lee, Jae Lyun; McKay, Rana R; Fay, André P; De Velasco, Guillermo; Heng, Daniel Y C; Choueiri, Toni K

    2016-02-01

    Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies. The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks. Overall, 198 (23.8%) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77%), and it was followed by sorafenib (18.4%). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age ≥60 years, a glomerular filtration rate (GFR) factors to predict the risk of TrTD. In the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice. © 2015 American Cancer Society.

  1. Quality control system to support comparability assessment for the Renal Bio-Replacement therapy system.

    Science.gov (United States)

    Pitkin, Z

    2005-01-01

    Cell therapies offer great promise for treating serious and life-threatening diseases, as cells provide the dynamic, interactive therapy that responds to the patient's condition. The spectrum of cell therapies is very broad, but each requires characterization during product development. During the development of a cell therapy, changes are made to improve product quality, purity, yield, and consistency, as well as to meet other production requirements. Multiple factors have to be considered when changes are made. A well thought-out design of comparability protocols has to reflect the international consensus set forth by the International Conference on Harmonization (ICH) and Food and Drug Administration (FDA). Comparability studies, due to their importance for the entire product development, constitute an additional challenge for the Quality System, which supports manufacturing. A comparability study was conducted to support the transfer of a cell-based technology, the Renal Bio-Replacement (RBR) system, from an academic laboratory to a contract manufacturing facility. The quality control programme supporting the RBR, and issues encountered in the comparability of the RBR therapy system, are discussed in this article.

  2. Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study.

    Science.gov (United States)

    Garcia-Donas, Jesus; Esteban, Emilio; Leandro-García, Luis Javier; Castellano, Daniel E; del Alba, Aranzazu González; Climent, Miguel Angel; Arranz, José Angel; Gallardo, Enrique; Puente, Javier; Bellmunt, Joaquim; Mellado, Begoña; Martínez, Esther; Moreno, Fernando; Font, Albert; Robledo, Mercedes; Rodríguez-Antona, Cristina

    2011-11-01

    Sunitinib is a tyrosine kinase inhibitor with proven efficacy in renal-cell carcinoma, but some patients do not respond or need dose reductions due to toxicity. Because there are no validated molecular predictors of response or toxicity to sunitinib, we aimed to identify genetic markers predictive of outcome and toxic effects. In our observational, prospective study we enrolled previously untreated adults (≥ 18 years) with clear-cell renal-cell carcinoma at 15 institutions in the Spanish Oncology Genitourinary Group in Spain. Patients received sunitinib according to local practice guidelines. We assessed RECIST response, progression-free survival (PFS), overall survival, and toxicity of sunitinib with 16 key polymorphisms in nine genes: VEGFR2 (rs2305948 and rs1870377), VEGFR3 (rs307826, rs448012, and rs307821), PDGFR-α (rs35597368), VEGF-A (rs2010963, rs699947, and rs1570360), IL8 (rs1126647), CYP3A4 (rs2740574), CYP3A5 (rs776746), ABCB1 (rs1045642, rs1128503, and rs2032582), and ABCB2 (rs2231142). We assessed associations with efficacy and toxicity by use of univariable and multivariable analyses (with clinical factors associated with outcomes as covariates). We adjusted for multiplicity using the Bonferroni method; p values of less than 0·0031 before adjustment were deemed to still be significant after adjustment. We enrolled 101 patients between Oct 10, 2007, and Dec 13, 2010. 95 of these patients were included in toxicity analyses and 89 in the efficacy analyses. Two VEGFR3 missense polymorphisms were associated with reduced PFS with sunitinib on multivariable analysis: rs307826 (hazard ratio [HR] per allele 3·57, 1·75-7·30; p(unadjusted)=0·00049, p(adjusted)=0·0079) and rs307821 (3·31, 1·64-6·68; p(unadjusted)=0·00085, p(adjusted)=0·014). The CYP3A5*1 (rs776746) high metabolising allele was associated in a multivariable analysis with an increased risk of dose reductions due to toxicity (HR per allele 3·75, 1·67-8·41; p(unadjusted)=0·0014, p

  3. Comparable Renal Function at 6 Months with Tacrolimus Combined with Fixed-Dose Sirolimus or MMF: Results of a Randomized Multicenter Trial in Renal Transplantation.

    Science.gov (United States)

    Van Gurp, Eveline; Bustamante, Jesus; Franco, Antonio; Rostaing, Lionel; Becker, Thomas; Rondeau, Eric; Czajkowski, Zenon; Rydzewski, Andrzej; Alarcon, Antonio; Bachleda, Petr; Samlik, Jiri; Burmeister, Dirk; Pallardo, Luis; Moal, Marie-Christine; Rutkowski, Boleslaw; Wlodarczyk, Zbigniew

    2010-01-01

    In a multicenter trial, renal transplant recipients were randomized to tacrolimus with fixed-dose sirolimus (Tac/SRL, N = 318) or tacrolimus with MMF (Tac/MMF, N = 316). Targeted tacrolimus trough levels were lower in the Tac/SRL group after day 14. The primary endpoint was renal function at 6 months using creatinine clearance (Cockcroft-Gault) and was comparable at 66.4 mL/min (SE 1.4) with Tac/SRL and at 65.2mL/min (SE 1.3) with Tac/MMF (completers). Biopsy-confirmed acute rejection was 15.1% (Tac/SRL) and 12.3% (Tac/MMF). In both groups, graft survival was 93% and patient survival was 99.0%. Premature withdrawal due to an adverse event was twice as high in the Tac/SRL group, 15.1% versus 6.3%. Hypercholesterolemia incidence was higher with Tac/SRL (P MMF (P 30 consecutive days in previously nondiabetic patients was 17.8%, Tac/SRL, and 24.8%, Tac/MMF. Evaluation at 6 months showed comparable renal function using tacrolimus/sirolimus and tacrolimus/MMF regimens.

  4. Comparative study between intravenous urography and renal scintigraphy with DMSA for the diagnosis of renal scars in children with vesicoureteral reflux

    Directory of Open Access Journals (Sweden)

    Clarissa B. Araújo

    2003-12-01

    Full Text Available PURPOSE: To assess the value of intravenous urography (IVU in detecting and grading the renal scar, comparing its results with those of scintigraphy with dimercaptosuccinic acid (DMSA. MATERIALS AND METHODS: The study included 43 children investigated by DMSA and IVU, who had vesicoureteral reflux diagnosed and classified through voiding cystourethrography. RESULTS: Among the kidneys with reflux, there was agreement between the results of DMSA and IVU concerning the presence and the absence of scars in 82.4% of the cases. Based on the results obtained, IVU would have a sensitivity of 66.6%, specificity of 94.4%; accuracy of 82.5%; positive predictive value (PPV of 90% and negative predictive value (NPV of 79%, when compared with DMSA results. Our data also confirm the close relation between the reflux grade and the presence of renal scar, since 75% of the kidneys with grade IV and V reflux presented scars. In relation to the grading of nephropathy, in 78% of patients the classification of the scar by both methods was identical. The highest disagreement was verified in the group with segmental scar on DMSA, where 41.6% of the kidneys were classified as normal on IVU. CONCLUSION: The data obtained confirm that the scintigraphy with DMSA is essential in the investigation of patients with renal scar, and cannot be replaced by IVU, due to its low sensitivity and lower ability of satisfactory grading.

  5. Oliguric and non-oliguric acute renal failure in malaria in west zone of rajasthan, India-A comparative study

    Institute of Scientific and Technical Information of China (English)

    Bal Kishan Gupta; Kailash Chandra Nayak; Sunil Kumar; Surendra Kumar; Anjli Gupta; Parul Prakash

    2012-01-01

    Objective: To report a comparative clinical and histopathological study on oliguric and non-oliguric acute renal failure (ARF) in malaria. Method: 311 consecutive cases of malaria out of which 74 (23.79%) had ARF as per WHO criteria were conducted. Mean age was 32.58 (range 15-60 years) and male: female was 2:1. Result: Most of the cases developed ARF within 10 d of onset. 18 cases (11 falciparum, 2 mixed, 5 vivax) presented with oliguric and 56 (41 falciparum, 6 mixed, 9 vivax) with non-oliguric renal failure. Associated major manifestations were jaundice (75.68%), cerebral malaria (41.89%), bleeding manifestations (32.43%), severe anemia (27.03%), hypotension (25.68%), multi-organ failure (18.92%), severe thrombocytopenia (12.16%), and ARDS (8.11%). Kidney biopsy (n=20) showed acute tubular necrosis (n=7), Mesangioproliferative glomerulonephritis (n=4) or both (n=9). Hemodialysis was done in 8 cases of oliguric renal failure out of which 4 survived (average no. of session 2.9). Conclusion: Most of the cases recovered within 3 weeks. Total mortality was 28.38% (n=21) and mortality was more in oliguric renal failure (72.22%) as compare to non-oliguric renal failure (14.29%).

  6. USEtox human exposure and toxicity factors for comparative assessment of toxic emissions in life cycle analysis: sensitivity to key chemical properties

    DEFF Research Database (Denmark)

    Rosenbaum, Ralph K.; Huijbregts, Mark; Henderson, Andrew D.

    2011-01-01

    Purpose The aim of this paper is to provide science-based consensus and guidance for health effects modelling in comparative assessments based on human exposure and toxicity. This aim is achieved by i) describing the USEtoxTM exposure and toxicity models representing consensus and recommended...... modelling practice, ii) identifying key mechanisms influencing human exposure and toxicity effects of chemical emissions, iii) extending substance coverage. Methods The methods section of this paper contains a detailed documentation of both the human exposure and toxic effects models of USEtox......TM, to determine impacts on human health per kg substance emitted in different compartments. These are considered as scientific consensus and therefore recommended practice for comparative toxic impact assessment. The framework of the exposure model is described in details including the modelling of each exposure...

  7. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

    Directory of Open Access Journals (Sweden)

    Ying-Mei Niu

    2016-01-01

    Full Text Available We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n=60. Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P<0.05 at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P<0.05 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P<0.05 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity.

  8. Toxicity of various silver nanoparticles compared to silver ions in Daphnia magna

    Directory of Open Access Journals (Sweden)

    Asghari Saba

    2012-04-01

    Full Text Available Abstract Background To better understand the potential ecotoxicological impacts of silver nanoparticles released into freshwater environments, the Daphnia magna 48-hour immobilization test was used. Methods The toxicities of silver nitrate, two types of colloidal silver nanoparticles, and a suspension of silver nanoparticles were assessed and compared using standard OECD guidelines. Also, the swimming behavior and visible uptake of the nanoparticles by Daphnia were investigated and compared. The particle suspension and colloids used in the toxicity tests were well-characterized. Results The results obtained from the exposure studies showed that the toxicity of all the silver species tested was dose and composition dependent. Plus, the silver nanoparticle powders subsequently suspended in the exposure water were much less toxic than the previously prepared silver nanoparticle colloids, whereas the colloidal silver nanoparticles and AgNO3 were almost similar in terms of mortality. The silver nanoparticles were ingested by the Daphnia and accumulated under the carapace, on the external body surface, and connected to the appendages. All the silver species in this study caused abnormal swimming by the D. magna. Conclusion According to the present results, silver nanoparticles should be classified according to GHS (Globally Harmonized System of classification and labeling of chemicals as "category acute 1" to Daphnia neonates, suggesting that the release of nanosilver into the environment should be carefully considered.

  9. Comparative Toxicity of Combined Particle and Semi-Volatile Organic Fractions of Gasoline and Diesel Emissions

    Energy Technology Data Exchange (ETDEWEB)

    Mauderly, Joe; Seagrave, JeanClare; McDonald, Jacob; Gigliotti,Andrew; Nikula, Kristen; Seilkop, Steven; Gurevich, Michael

    2002-08-25

    Little is known about the relative health hazards presented by emissions from in-use gasoline and diesel engines. Adverse health effects have been ascribed to engine emissions on the basis of: (1) the presence of known toxic agents in emissions; (2) high-dose animal and bacterial mutagenicity tests; and (3) studies indicating gradients of health effects with proximity to roadways. Most attention has been given to the particulate fraction of emissions; little attention has been given to the semi-volatile organic fraction. However, the semi-volatile fraction overlaps the particulate fraction in composition and is always present in the vicinity of fresh emissions. Although the potential health effects of diesel emissions have been frequently studied and debated during the past 20 years (EPA, 2002), relatively little attention has been given to the toxicity of emissions from gasoline engines. In view of the considerable progress in cleaning up diesel emissions, it would be useful to compare the toxicity of emissions from contemporary on-road diesel technology with that of emissions from the in-use gasoline fleet that is well-accepted by the public. It would also be useful to have a set of validated tests for rapid, cost-effective comparisons of the toxicity of emission samples, both for comparisons among competing technologies (e.g., diesel, gasoline, natural gas) and for determining the impacts of new fuel, engine, and after-treatment strategies on toxicity. The Office of Heavy Vehicle Technologies has sponsored research aimed at developing and applying rapid-response toxicity tests for collected emission samples (Seagrave et al., 2000). This report presents selected results from that work, which is being published in much greater detail in the peer-reviewed literature (Seagrave et al., 2002).

  10. Evaluation of Short-Term Bioassays to Predict Functional Impairment. Selected Short-Term Renal Toxicity Tests.

    Science.gov (United States)

    1980-10-01

    Axelsson and Piscator , 1966). In human clinical studies (Peterson et al., 1969; Hall, 1973), a low molecular weight beta 2-globulin (beta 2...glycerol-induced myohemoglobinuric acute renal fail- ure in the rat." Circulation Research 29:128-135. Axelsson, B. and M. Piscator , 1966. "Renal damage

  11. Comparing the effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on renal function decline in diabetes

    NARCIS (Netherlands)

    Huang, Yunyu; Haaijer-Ruskamp, Flora M.; Voorham, Jaco

    2016-01-01

    Aim: To compare effectiveness of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) for protecting Type 2 diabetes mellitus (DM2) patients from renal function decline in a real-world setting. Methods: Retrospective cohort study of new ACEi/ARB users in 2007-2012 in

  12. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

    OpenAIRE

    Ying-Mei Niu; Xiao-Li Zhu; Bing Chang; Zhao-Hui Tong; Wen Cao; Pei-Huan Qiao; Lin-Yuan Zhang; Jing Zhao; Yu-Guo Song

    2016-01-01

    We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P < 0.05) at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P < 0.05) 24 hr. after expo...

  13. Toward a comparative overview of dependence potential and acute toxicity of psychoactive substances used nonmedically.

    Science.gov (United States)

    Gable, R S

    1993-01-01

    A procedure is outlined for comparing dependence potential and acute toxicity across a broad range of abused psychoactive substances. Tentative results, based on an extensive literature review of 20 substances, suggested that the margin of safety ("therapeutic index") varied dramatically between substances. Intravenous heroin appeared to have the greatest risk of dependence and acute lethality; oral psilocybin appeared to have the least. Hazards due to behavioral deficits, perceptual distortion, or chronic illness were not factored into the assessments.

  14. Comparative toxicities of oxygen, ozone, chlorine dioxide, and chlorine bleaching filtrates - microtox toxicities of raw and processed filtrates

    Energy Technology Data Exchange (ETDEWEB)

    Ard, T.A.; McDonough, T.J.

    1995-12-31

    It has claimed that effluents from the bleaching of kraft pulp with chlorine and its compounds have deleterious effects on the aquatic environment. It has been further suggested that bleaching without the use of chlorine or its compounds will produce innocuous effluents. To obtain information on the validity of these claims, we have conducted a laboratory study of the toxicity of filtrates from chlorine-based and nonchlorine bleaching processes. We have also examined two related issues. The first is whether any toxicants generated during bleaching are rendered harmless (by neutralization, storage, and biological treatment) before being discharged to the environment. The second related issue is whether any toxicity observed in mill effluents actually originates in the bleaching process, as opposed to being due to raw material components or compounds formed during the pulping step that precedes bleaching. Several conclusions were drawn from this study. (1) There is a background level of toxicity which originates in the oxygen stage, process steps prior to bleaching, or in the wood raw material. It is decreased by neutralization and storage, but residual toxicity may still be detected after two weeks. (2) If the sum of the first and second stage toxicities is taken as an indicator of overall toxicity, the untreated filtrates may be ranked as follows: Control (Background) > D(EO) > Z(EO) > C(EO). However, these toxicities are of no importance in regard to environmental effects because of their ephemeral nature and the likelihood of their being reduced or eliminated prior to effluent discharge. Evidence for this statement is the ease with which all except the C(EO) were detoxified by neutralization and storage. (3) After neutralization and storage for two weeks at room temperature the ranking of toxicities becomes: C(EO) > D(EO) > Z(EO) > Background. The last three are similar in magnitude.

  15. The rate of progression of renal disease may not be slower in women compared with men

    DEFF Research Database (Denmark)

    Jafar, Tazeen H; Schmid, Christopher H; Stark, Paul C

    2003-01-01

    of renal disease progression with gender. METHODS: We analysed a pooled database of patients with non-diabetic renal disease enrolled in 11 randomized controlled trials evaluating the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) for slowing renal disease progression. The primary end point...... patient characteristics, and changes from baseline to follow-up systolic blood pressure (SBP) and urine protein (UP) excretion. RESULTS: The total number of patients was 1860: 645 (35%) females and 1215 (65%) males. Mean duration of follow-up was 2.2 years. The proportions randomized to ACEI (51%), mean...... ACEIs and baseline UP, and 1.36 (1.06-1.75) after adjusting for baseline variables and changes in SBP and UP during follow-up. Similar results were found for the outcome of ESRD. CONCLUSIONS: Our findings suggest that the rate of renal disease progression may not be slower, and may even be faster...

  16. Influence of renal function on the pharmacokinetics of lomefloxacin compared with other fluoroquinolones.

    Science.gov (United States)

    Blum, R A

    1992-04-06

    Fluoroquinolones have similar chemical structures but wide differences in their pharmacokinetic profiles. Disparity in fluoroquinolone elimination is most evident in patients with various degrees of renal insufficiency. Ofloxacin is almost exclusively eliminated by the kidney, whereas pefloxacin is predominantly cleared by the liver. The fluoroquinolones eliminated by both renal and nonrenal routes (hepatic and transintestinal) include norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin. The primary renal mechanism of elimination for norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin is glomerular filtration and tubular secretion. Both total clearance and renal clearance significantly correlate with creatinine clearance for these fluoroquinolones, and creatinine clearance is a useful clinical marker on which to base dosage adjustments. For some fluoroquinolones, dosage adjustments are recommended when creatinine clearances fall below 30-40 mL/min. This is especially evident for lomefloxacin, temafloxacin, norfloxacin, ciprofloxacin, enoxacin, and fleroxacin. There is very little removal of fluoroquinolones from the plasma during hemodialysis due to their extensive tissue distribution.

  17. A comparative study of renal care in Brazil and Mexico: hemodialysis treatment from the perspective of ESRD sufferers.

    Science.gov (United States)

    Mercado-Martinez, Francisco J; da Silva, Denise Guerreiro V; Correa-Mauricio, Mauricio E

    2017-04-01

    Renal replacement therapy is the indicated treatment for individuals with chronic kidney disease (CKD) to survive. However, not all sick people have access to the same treatment. This study compares renal care in two developing countries with different health systems. Specifically, it explores hemodialysis treatment from the perspective of low-income individuals. A qualitative, comparative study was performed in Brazil and Mexico. Using purposive sampling, the research was based on open-ended interviews with nineteen participants with kidney failure undergoing hemodialysis treatment in public hospitals and ten relatives. According to our results, Brazilian participants perceived hemodialysis care as satisfactory because of health personnel courtesy as well as free access to dialysis treatment, prescription drugs, hospitalization and transportation. However, they reported deficiencies in the care they were receiving due to shortages of specialists, prescription drugs, laboratory tests and transportation. Mexican participants, in contrast, highlighted the catastrophic costs of medical care because they had no free access to renal therapy, nor adequate financial resources. Our findings suggest that low-income Brazilian CKD sufferers experience renal care differently, as they are more satisfied and face less obstacles with hemodialysis compared with those of Mexico. More studies on the topic are needed. © 2016 John Wiley & Sons Ltd.

  18. A STUDY OF EFFICACY AND SAFETY OF TACROLIMUS COMPARED WITH CYCLOSPORIN A MICROEMULSION IN RENAL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Jayakumar Edathedathe Krishnan

    2016-11-01

    Full Text Available BACKGROUND The aim of this retrospective study was to compare therapeutic efficacy and safety profile of Cyclosporin and Tacrolimus in posttransplant patients with respect to graft function and metabolic disorders. MATERIALS AND METHODS Data of patients who underwent renal transplant in Calicut Medical College during July 2014 to December 2015 was collected and baseline parameters like BP, Blood glucose, cholesterol, RFT and LFT levels were assessed at 2 weeks, 1 month, 6 months and at 1 year in one year completed subgroup. Incidence of delayed graft function and acute rejection were also included. RESULTS Clinical data of 60 patients (32 in Cyclosporin group and 28 in Tacrolimus group were collected. Among the 60 patients, 32 patients (16 in Cyclosporin group and 16 in Tacrolimus group completed one year. The incidence of acute rejection with Cyclosporin group and with Tacrolimus group was 14.7% and 13.6% and 31.2% and 25% at 6 months and 1 year respectively. At one year in the subgroup for 32 patients, serum creatinine was 17 was seen in 6.25% (1/16 in Cyclosporin group and none in Tacrolimus group. Dyslipidaemia was observed in 56.3% (9/16 in Cyclosporin group and 32.5% (6/16 in Tacrolimus group. At one year, hirsutism was 18.7% with Cyclosporin group and 0% with Tacrolimus group. CONCLUSION No statistically significant difference in graft function & incidence of acute rejection between the two treatment groups at 6 months & 1 year.

  19. Comparative Cellular Toxicity of Hydrophilic and Hydrophobic Microcystins on Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Jussi A. O. Meriluoto

    2012-10-01

    Full Text Available Microcystins (MC, cyanobacterial peptide hepatotoxins, comprise more than 100 different variants. They are rather polar molecules but some variants contain hydrophobic amino acid residues in the highly variable parts of the molecule. In MC-LF and MC-LW, the more hydrophobic phenylalanine (F and tryptophan (W, respectively, have replaced arginine (R in MC-LR. Depending on the structure, microcystins are expected to have different in vivo toxicity and bioavailability, but only a few studies have considered the toxic properties of the more hydrophobic variants. The present study shows that MC-LF and MC-LW have more pronounced cytotoxic effects on Caco-2 cells as compared to those of MC-LR. Treatment of Caco-2 cells with MC-LW and especially MC-LF showed clear apoptotic features including shrinkage and blebbing, and the cell–cell adhesion was lost. An obvious reduction of cell proliferation and viability, assessed as the activity of mitochondrial dehydrogenases, was observed with MC-LF, followed by MC-LW and MC-LR. Cytotoxicity was quantified by measuring lactate dehydrogenase leakage. The more hydrophobic MC-LW and MC-LF induced markedly enhanced lactate dehydrogenase leakage compared to controls and MC-LR, indicating that the plasma membrane was damaged. All of the three toxins examined inhibited protein phosphatase 1, with MC-LF and MC-LW to a weaker extent compared to MC-LR. The higher toxic potential of the more hydrophobic microcystins could not be explained by the biophysical experiments performed. Taken together, our data show that the more hydrophobic microcystin variants induce higher toxicity in Caco-2 cells.

  20. Comparative cellular toxicity of hydrophilic and hydrophobic microcystins on Caco-2 cells.

    Science.gov (United States)

    Vesterkvist, Pia S M; Misiorek, Julia O; Spoof, Lisa E M; Toivola, Diana M; Meriluoto, Jussi A O

    2012-10-25

    Microcystins (MC), cyanobacterial peptide hepatotoxins, comprise more than 100 different variants. They are rather polar molecules but some variants contain hydrophobic amino acid residues in the highly variable parts of the molecule. In MC-LF and MC-LW, the more hydrophobic phenylalanine (F) and tryptophan (W), respectively, have replaced arginine (R) in MC-LR. Depending on the structure, microcystins are expected to have different in vivo toxicity and bioavailability, but only a few studies have considered the toxic properties of the more hydrophobic variants. The present study shows that MC-LF and MC-LW have more pronounced cytotoxic effects on Caco-2 cells as compared to those of MC-LR. Treatment of Caco-2 cells with MC-LW and especially MC-LF showed clear apoptotic features including shrinkage and blebbing, and the cell–cell adhesion was lost. An obvious reduction of cell proliferation and viability, assessed as the activity of mitochondrial dehydrogenases, was observed with MC-LF, followed by MC-LW and MC-LR. Cytotoxicity was quantified by measuring lactate dehydrogenase leakage. The more hydrophobic MC-LW and MC-LF induced markedly enhanced lactate dehydrogenase leakage compared to controls and MC-LR, indicating that the plasma membrane was damaged. All of the three toxins examined inhibited protein phosphatase 1, with MC-LF and MC-LW to a weaker extent compared to MC-LR. The higher toxic potential of the more hydrophobic microcystins could not be explained by the biophysical experiments performed. Taken together, our data show that the more hydrophobic microcystin variants induce higher toxicity in Caco-2 cells.

  1. Comparative pulmonary toxicity of inhaled metalworking fluids in rats and mice.

    Science.gov (United States)

    Ryan, Kristen R; Cesta, Mark F; Herbert, Ronald; Brix, Amy; Cora, Michelle; Witt, Kristine; Kissling, Grace; Morgan, Daniel L

    2017-05-01

    Metalworking fluids (MWFs) are complex formulations designed for effective lubricating, cooling, and cleaning tools and parts during machining operations. Adverse health effects such as respiratory symptoms, dermatitis, and cancer have been reported in workers exposed to MWFs. Several constituents of MWFs have been implicated in toxicity and have been removed from the formulations over the years. However, animal studies with newer MWFs demonstrate that they continue to pose a health risk. This investigation examines the hypothesis that unrecognized health hazards exist in currently marketed MWF formulations that are presumed to be safe based on hazard assessments of individual ingredients. In vivo 13-week inhalation studies were designed to characterize and compare the potential toxicity of four MWFs: Trim VX, Cimstar 3800, Trim SC210, and Syntilo 1023. Male and female Wistar Han rats or Fischer 344N/Tac rats and B6C3F1/N mice were exposed to MWFs via whole-body inhalation at concentrations of 0, 25, 50, 100, 200, or 400 mg/m(3) for 13 weeks, after which, survival, body and organ weights, hematology and clinical chemistry, histopathology, and genotoxicity were assessed following exposure. Although high concentrations were used, survival was not affected and toxicity was primarily within the respiratory tract of male and female rats and mice. Minor variances in toxicity were attributed to differences among species as well as in the chemical components of each MWF. Pulmonary fibrosis was present only in rats and mice exposed to Trim VX. These data confirm that newer MWFs have the potential to cause respiratory toxicity in workers who are repeatedly exposed via inhalation.

  2. Severe Late Toxicities Following Concomitant Chemoradiotherapy Compared to Radiotherapy Alone in Cervical Cancer: An Inter-era Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gondi, Vinai, E-mail: gondi@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin (United States); Bentzen, Soren M.; Sklenar, Kathryn L.; Dunn, Emily F. [Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin (United States); Petereit, Daniel G. [Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin (United States); John T. Vucurevich Cancer Care Institute, Rapid City Regional Hospital, Rapid City, South Dakota (United States); Tannehill, Scott P. [Arizona Cancer Specialists, Phoenix, Arizona (United States); Department of Radiation Oncology, University of Arizona, Tuscon, Arizona (United States); Straub, Margaret; Bradley, Kristin A. [Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin (United States)

    2012-11-15

    Purpose: To compare rates of severe late toxicities following concomitant chemoradiotherapy and radiotherapy alone for cervical cancer. Methods and Materials: Patients with cervical cancer were treated at a single institution with radiotherapy alone or concomitant chemoradiotherapy for curative intent. Severe late toxicity was defined as grade {>=}3 vaginal, urologic, or gastrointestinal toxicity or any pelvic fracture, using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE), occurring {>=}6 months from treatment completion and predating any salvage therapy. Severe late toxicity rates were compared after adjusting for pertinent covariates. Results: At 3 years, probability of vaginal severe late toxicity was 20.2% for radiotherapy alone and 35.1% for concomitant chemoradiotherapy (P=.026). At 3 years, probability of skeletal severe late toxicity was 1.6% for radiotherapy alone and 7.5% for concomitant chemoradiotherapy (P=.010). After adjustment for case mix, concomitant chemoradiotherapy was associated with higher vaginal (hazard ratio [HR] 3.0, 95% confidence interval [CI], 1.7-5.2, P<.001), and skeletal (HR 7.0, 95% CI 1.4-34.1, P=.016) severe late toxicity. Compared to high dilator compliance, moderate (HR 3.6, 95% CI 2.0-6.5, P<.001) and poor (HR 8.5, 95% CI 4.3-16.9, P<.001) dilator compliance was associated with higher vaginal severe late toxicity. Age >50 was associated with higher vaginal (HR 1.8, 95% CI 1.1-3.0, P=.013) and skeletal (HR 5.7, 95% CI 1.2-27.0, P=.028) severe late toxicity. Concomitant chemoradiotherapy was not associated with higher gastrointestinal (P=.886) or urologic (unadjusted, P=.053; adjusted, P=.063) severe late toxicity. Conclusion: Compared to radiotherapy alone, concomitant chemoradiotherapy is associated with higher rates of severe vaginal and skeletal late toxicities. Other predictive factors include dilator compliance for severe vaginal late toxicity and age for severe vaginal and skeletal late toxicities.

  3. Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients

    Science.gov (United States)

    Pilanci, Kezban N.; Avcı, Nilüfer; Yıldız, İbrahim; Alço, Gül; Demirhan, Özkan; Köksal, Ülkühan I.; Elbüken, Filiz; Tecimer, Coskun; Demir, Gökhan

    2016-01-01

    Aim of the study Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12–61) and 19 months (5–45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. Conclusions As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients. PMID:27358594

  4. Glutaraldehyde Treatment Elicits Toxic Response Compared to Decellularization in Bovine Pericardium

    Science.gov (United States)

    Umashankar, P.R.; Mohanan, P.V.; Kumari, T.V.

    2012-01-01

    Glutaraldehyde-stabilized bovine pericardium is used for clinical application since 1970s because of its desirable features such as less immunogenicity and acceptable durability. However, a propensity for calcification is reported on account of glutaraldehyde treatment. In this study, commercially available glutaraldehyde cross-linked bovine pericardium was evaluated for its in vitro cytotoxic effect, macrophage activation, and in vivo toxic response in comparison to decellularized bovine pericardium. Glutaraldehyde-treated bovine pericardium and its extract were observed to be cytotoxic and it also caused significant inflammatory cytokine release from activated macrophages. Significant antibody response, calcification response, necrotic, and inflammatory response were noticed in glutaraldehyde-treated bovine pericardium in comparison to decellularized bovine pericardium in a rat subcutaneous implantation model. Glutaraldehyde-treated bovine pericardium also failed in acute systemic toxicity testing and intracutaneous irritation testing as per ISO 10993. With respect to healing and implant remodeling, total lack of host tissue incorporation and angiogenesis was noticed in glutaraldehyde-treated bovine pericardium compared to excellent host fibroblast incorporation and angiogenesis within the implant in decellularized bovine pericardium. In conclusion, using in vitro and in vivo techniques, this study has demonstrated that glutaraldehyde-treated bovine pericardium elicits toxic response compared to decellularized bovine pericardium which is not congenial for long-term implant performance. PMID:22736904

  5. Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse.

    Directory of Open Access Journals (Sweden)

    Stefano Toldo

    Full Text Available PURPOSE: The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo. METHODS: The cardiomyocytes were incubated with the three anthracyclines (1 µM to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF, heart rate (HR and cardiac output (CO both prior to and 10 days after drug treatment. RESULTS: In HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS, as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin. CONCLUSION: This study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin.

  6. The use of pharmacokinetically guided indinavir dose reductions in the management of indinavir-associated renal toxicity.

    NARCIS (Netherlands)

    Boyd, M.A.; Siangphoe, U.; Ruxrungtham, K.; Reiss, P.; Mahanontharit, A.; Lange, J.M.A.; Phanuphak, P.; Cooper, D.A.; Burger, D.M.

    2006-01-01

    OBJECTIVES: Indinavir is associated with nephrotoxicity. Therapeutic drug monitoring of indinavir improves clinical outcome, but there is little data regarding therapeutic drug monitoring for patients with established indinavir-associated renal impairment. We prospectively studied the use of therape

  7. Comparative residual toxicities of pesticides to the predator Agistemus industani (Acari: Stigmaeidae) on citrus in Florida.

    Science.gov (United States)

    Childers, C C; Villanueva, R; Aguilar, H; Chewning, R; Michaud, J P

    2001-01-01

    Residual toxicities of registered and selected experimental pesticides used on citrus against Agistemus industani Gonzalez (Acari: Stigmaeidae) were compared. Pesticides considered highly toxic to A. industani were: abamectin 0.15 EC at 731 ml/ha + FC 435-66 petroleum oil at 46.8 l/ha, pyridaben 75 WP at 469 g/ha, ethion 4 EC at 7.01 l/ha + FC 435-66 petroleum oil at 46.8 l/ha, propargite 6.55 EC at 3.51 l/ha, chlorfenapyr 2 SC at 1.46 l/ha applied alone or in combination with FC 435-66 petroleum oil at 46.8 l/ha, sulphur 80 DF at 16.81 kg/ha. dicofol 4EC at 7.01 l/ha, fenbutatin oxide 50 WP at 2.24 kg/ha, benomyl 50 WP at 2.24 kg/ha, benomyl 50 WP at 1.68 kg/ha + ferbam 76 GF at 5.60 kg/ha, ferbam 76 GF at 11.21 kg/ha, neem oil 90 EC at 46.8 l/ha, and copper hydroxide DF (40% metallic copper) at 4.48 kg metallic copper/ha + FC 435-66 petroleum oil at 46.8 l/ha. Pesticides that were moderately to slightly toxic included: copper sulphate 98% at 4.48 kg metallic copper/ha + FC 435-66 petroleum oil at 46.8 l/ha, fenbuconazole 2 F at 280 ml/ha + FC 435-66 petroleum oil at 46.8 l/ha, FC 435-66 petroleum oil applied alone at 46.8 l/ha or 23.41/ha, and diflubenzuron 25 WP at 1.40 kg/ha. Pesticides that were non-toxic included: fenbuconazole 2 F at 585 ml/ha, malathion 57 EC at 5.85 l/ha, FC 435-66 petroleum oil at 46.8 l/ha, carbaryl 80 S at 3.36 kg/ha. chlorpyrifos 4 EC at 4.68 l/ha, and formetanate 92 SP at 1.12 kg/ha. Understanding the toxic effects of field weathered pesticides against key predacious mite species is important for effective IPM. The results of this study provide a comparison of direct and indirect toxic effects of various pesticides to A. industani under field conditions.

  8. Comparative study of the nutritional composition and toxic elements of farmed and wild Chanodichthys mongolicus

    Science.gov (United States)

    Jiang, Haifeng; Cheng, Xiaofei; Geng, Longwu; Tang, Shizhan; Tong, Guangxiang; Xu, Wei

    2016-09-01

    Information of the difference in quality between farmed and wild fish is central to better ensuring fish products produced in aquaculture meet regulatory and consumer requirements. Proximate composition, amino acid and fatty acid profiles, and toxic elements contents of farmed and wild C. mongolicus were established and compared. Significantly higher crude protein content while lower moisture content in farmed fish compared to wild fish were observed (P values, the ratios of TEAA/TAA (39.84%-40.33%) were comparable to 40% and TEAA / TNEAA (66.22%-67.60%) were above 60%. Fatty acid profiles in both farmed and wild C. mongolicus were dominated by monounsaturated fatty acid (MUFA), with farmed fish contained much more MUFA content compared to wild counterpart (P nutritional quality of farmed C. mongolicus was inferior to their wild counterpart with respect to fatty acids nutrition, and therefore further studies should focus on the improving C. mongolicus diet in order to enhance the overall nutritional composition.

  9. Comparative study on toxicity evaluation of anaerobically treated parboiled rice manufacturing wastewater through fish bioassay.

    Science.gov (United States)

    Giri, Dipti Ramesh; Singh, Ekta; Satyanarayan, Shanta

    2016-01-01

    Short term aquatic bioassay has been developed into a useful tool in water quality management. These tests give information on comparative toxicity of several compounds. The objective of this study was to evaluate the acute toxicity of raw and anaerobically treated effluents of the parboiled rice manufacturing industry. The acute toxicity test was carried out by using the fish Lebistes reticulatus under laboratory conditions. LC50 values for 24, 48, 72 and 96 hours ranged between 4.6 and 7.0% for the raw parboiled rice manufacturing wastewater. Two anaerobic fixed film fixed bed reactors and two different media matrices, i.e. UV stabilized Biopac media and Fugino spirals, were used for the treatment of parboiled rice mill wastewater. Effluents from these two reactors depicted LC50 values in the range of 68-88% and 62-78% for Biopac and Fugino spiral packed reactors, respectively. From the results, it is evident that anaerobically treated effluents from Biopac packed reactor is marginally better than Fugino spiral packed reactor. Results subjected to statistical evaluation depicted regression coefficient of more than 0.9 indicating good correlation between the mortality and effluent concentration.

  10. Comparative Aquatic Toxicity of Gold Nanoparticles and Ionic Gold Using a Species Sensitivity Distribution Approach

    Directory of Open Access Journals (Sweden)

    Tarryn L. Botha

    2015-01-01

    Full Text Available Gold nanoparticles (nAu are used in drug delivery systems allowing for targeted cellular distribution. The effects of increased use and release of nanoparticles into the environment are not well known. A species sensitivity distribution (SSD allows for the ecotoxicological hazard assessment of a chemical based on single species toxicity tests. Aquatic toxicity needs to be related to particle characterization in order to understand the effects. The behaviour of nAu in the medium changed as the concentration increased. The toxic potential of ionic gold and nAu was expressed as a hazardous concentration where 5% of species will be harmed (HC5. The HC5 for nAu was much higher (42.78 mg/L compared to the ionic gold (2.44 mg/L. The differences between the hazard potentials of nAu and ionic gold were attributed to the nAu not releasing any Au ions into solution during the exposures and following an aggregation theory response. Exposures to ionic gold on the other hand followed a clear dose dependent response based on the concentration of the ionic metal. Although SSDs present an indication of the relative hazard potential of nanoparticles, the true worth can only be achieved once other nanoparticle characteristics and their behavior in the environment are also considered.

  11. Comparative evaluation of short-term toxicity of inorganic arsenic compounds on Artemia salina.

    Science.gov (United States)

    GuŢu, Claudia Maria; Olaru, Octavian Tudorel; Purdel, Nicoleta Carmen; Ilie, Mihaela; NeamŢu, Marius Cristian; Dănciulescu Miulescu, Rucsandra; Avramescu, Elena Taina; Margină, Denisa Marilena

    2015-01-01

    The study aimed to assess the short-term effects exerted by two inorganic arsenic species (arsenite and arsenate) on Artemia salina after 24, 48 and 72 h. The dose-lethality curves obtained indicate that the lethality induced by arsenite was higher than by arsenate. The lowest observed effect concentration for arsenite (0.5 μg/mL) is similar with the no observed effect concentration for arsenate, thus indicating that the toxicity of arsenite is higher compared with arsenate. Also, the lethal concentration 50 values confirm that arsenite induced about 1.24-fold higher toxicity than arsenate at 24 h and about three-fold higher toxicity at 48 h and 72 h of exposure. Both LC50 (lethal concentration 50) values are indicating negligible effects exhibited by arsenic at this trophic level after short-term exposure. The predicted no effect concentration in the surface aquatic compartment corresponds to 10.38 μg/L, similar to the limit imposed by Directive 98/83/EC.

  12. Addressing geographic variability in the comparative toxicity potential of copper and nickel in soils.

    Science.gov (United States)

    Owsianiak, Mikołaj; Rosenbaum, Ralph K; Huijbregts, Mark A J; Hauschild, Michael Z

    2013-04-02

    Comparative toxicity potentials (CTP), in life cycle impact assessment also known as characterization factors (CF), of copper (Cu) and nickel (Ni) were calculated for a global set of 760 soils. An accessibility factor (ACF) that takes into account the role of the reactive, solid-phase metal pool in the soil was introduced into the definition of CTP. Geographic differences in fate, accessibility, bioavailability, and terrestrial toxicity were assessed by combining the USEtox characterization model, empirical regression models, and terrestrial biotic ligand models. The median CTPs for Cu and Ni with 95% geographic variability intervals are 1.4 × 10(3) (1.7 × 10(2) to 2.0 × 10(4)) and 1.7 × 10(3) (2.1 × 10(2) to 1.1 × 10(4)) m(3)/kg · day, respectively. The geographic variability of 3.5 orders of magnitude in the CTP of Cu is mainly associated with the variability in soil organic carbon and pH. They largely influence the fate and bioavailability of Cu in soils. In contrast, the geographic variability of 3 orders of magnitude in the CTP of Ni can mainly be explained by differences in pore water concentration of magnesium (Mg(2+)). Mg(2+) competes with Ni(2+) for binding to biotic ligands, influencing the toxicity. Our findings stress the importance of dealing with geographic variability in the calculation of CTPs for terrestrial ecotoxicity of metals.

  13. Comparative toxicities and synergism of apple orchard pesticides to Apis mellifera (L. and Osmia cornifrons (Radoszkowski.

    Directory of Open Access Journals (Sweden)

    David J Biddinger

    Full Text Available The topical toxicities of five commercial grade pesticides commonly sprayed in apple orchards were estimated on adult worker honey bees, Apis mellifera (L. (Hymenoptera: Apidae and Japanese orchard bees, Osmia cornifrons (Radoszkowski (Hymenoptera: Megachilidae. The pesticides were acetamiprid (Assail 30SG, λ-cyhalothrin (Warrior II, dimethoate (Dimethoate 4EC, phosmet (Imidan 70W, and imidacloprid (Provado 1.6F. At least 5 doses of each chemical, diluted in distilled water, were applied to freshly-eclosed adult bees. Mortality was assessed after 48 hr. Dose-mortality regressions were analyzed by probit analysis to test the hypotheses of parallelism and equality by likelihood ratio tests. For A. mellifera, the decreasing order of toxicity at LD₅₀ was imidacloprid, λ-cyhalothrin, dimethoate, phosmet, and acetamiprid. For O. cornifrons, the decreasing order of toxicity at LD₅₀ was dimethoate, λ-cyhalothrin, imidacloprid, acetamiprid, and phosmet. Interaction of imidacloprid or acetamiprid with the fungicide fenbuconazole (Indar 2F was also tested in a 1∶1 proportion for each species. Estimates of response parameters for each mixture component applied to each species were compared with dose-response data for each mixture in statistical tests of the hypothesis of independent joint action. For each mixture, the interaction of fenbuconazole (a material non-toxic to both species was significant and positive along the entire line for the pesticide. Our results clearly show that responses of A. mellifera cannot be extrapolated to responses of O.cornifrons, and that synergism of neonicotinoid insecticides and fungicides occurs using formulated product in mixtures as they are commonly applied in apple orchards.

  14. Long-term renal allograft function on a tacrolimus-based, pred-free maintenance immunosuppression comparing sirolimus vs. MMF.

    Science.gov (United States)

    Gallon, L; Perico, N; Dimitrov, B D; Winoto, J; Remuzzi, G; Leventhal, J; Gaspari, F; Kaufman, D

    2006-07-01

    It is not known how different steroid-free immunosuppressive combinations affect renal graft survival and long-term kidney transplant function. Here we sought to compare the impact on graft survival and long-term graft function of two tacrolimus (Tac)-based, prednisone-free maintenance immunosuppressive protocols: Tac/Mycophenolate Mofetil (MMF) vs. Tac/Sirolimus (SRL). Renal transplant patients given induction therapy with IL2-RA and methylprednisolone on days 0, 1 and 2 post-transplant were prospectively randomized to two maintenance immunosuppressive regimens with Tac/MMF (n = 45) or Tac/SRL (n = 37). During the 3-year follow-up the following data were collected: patient survival, renal allograft survival, incidence of acute rejection and glomerular filtration rate (GFR) at different time-points post-transplant. Cumulative graft survival was significantly different in the two groups: one kidney loss in the Tac/MMF vs. six kidney losses in the Tac/SRL (log-rank test p = 0.04). GFR at different time-points post-transplant was consistently and statistically better in the Tac/MMF than in the Tac/SRL group. The slope of GFR decline per month was flatter in the Tac/MMF than in the Tac/SRL group. This study showed that renal graft survival and graft function were significantly lower in the combination of Tac/SRL than Tac/MMF.

  15. Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Witold Wiecek

    Full Text Available Renal-cell carcinoma (RCC affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC at diagnosis. Most mRCC patients treated with a first-line agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS data digitized from the Kaplan-Meier curves reported in the studies. Three models allowing hazard ratios (HR to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]. However, all models with time-varying HR showed better fits than the fixed-HR model. The log-logistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval <1 from 10 months. The initial probability of cabozantinib conferring superior OS was 54%, falling to 41.5% by month 24. Numerical differences in study-adjusted OS estimates between the two treatments remained small. This study evidences that HR for OS of nivolumab vs. cabozantinib varies over time, favoring cabozantinib in the first months of treatment but nivolumab afterwards, a possible indication that patients with poor prognosis benefit more from cabozantinib in terms of survival, nivolumab benefiting patients with better prognosis. More evidence, including real

  16. Compared in vivo toxicity in mice of lung delivered biodegradable and non-biodegradable nanoparticles.

    Science.gov (United States)

    Aragao-Santiago, Letícia; Hillaireau, Hervé; Grabowski, Nadège; Mura, Simona; Nascimento, Thais L; Dufort, Sandrine; Coll, Jean-Luc; Tsapis, Nicolas; Fattal, Elias

    2016-01-01

    To design nanoparticle (NP)-based drug delivery systems for pulmonary administration, biodegradable materials are considered safe, but their potential toxicity is poorly explored. We here explore the lung toxicity in mice of biodegradable nanoparticles (NPs) and compare it to the toxicity of non-biodegradable ones. NP formulations of poly(d,l-lactide-co-glycolide) (PLGA) coated with chitosan (CS), poloxamer 188 (PF68) or poly(vinyl alcohol) (PVA), which renders 200 nm NPs of positive, negative or neutral surface charge respectively, were analyzed for their biodistribution by in vivo fluorescence imaging and their inflammatory potential after single lung nebulization in mice. After exposure, analysis of bronchoalveolar lavage (BAL) cell population, protein secretion and cytokine release as well as lung histology were carried out. The inflammatory response was compared to the one induced by non-biodegradable counterparts, namely, TiO2 of rutile and anatase crystal form and polystyrene (PS). PLGA NPs were mostly present in mice lungs, with little passage to other organs. An increase in neutrophil recruitment was observed in mice exposed to PS NPs 24 h after nebulization, which declined at 48 h. This result was supported by an increase in interleukin (IL)-6 and tumor necrosis factor α (TNFα) in BAL supernatant at 24 h. TiO2 anatase NPs were still present in lung cells 48 h after nebulization and induced the expression of pro-inflammatory cytokines and the recruitment of polymorphonuclear cells to BAL. In contrast, regardless of their surface charge, PLGA NPs did not induce significant changes in the inflammation markers analyzed. In conclusion, these results point out to a safe use of PLGA NPs regardless of their surface coating compared to non-biodegradable ones.

  17. Switch to 1.5 grams MMF monotherapy for CNI-related toxicity in liver transplantation is safe and improves renal function, dyslipidemia, and hypertension.

    Science.gov (United States)

    Orlando, Giuseppe; Baiocchi, Leonardo; Cardillo, Andrea; Iaria, Giuseppe; De Liguori Carino, Nicola; De Liguori, Nicola; De Luca, Linda; Ielpo, Benedetto; Tariciotti, Laura; Angelico, Mario; Tisone, Giuseppe

    2007-01-01

    Although mycophenolate mofetil (MMF) monotherapy has been successfully used in liver transplant recipients suffering from calcineurin-inhibitor (CNI)-related chronic toxicity, still no consensus has been reached on its safety, efficacy and tolerability. We attempted the complete weaning off CNI in 42 individuals presenting chronic renal dysfunction and/or dyslipidemia and/or arterial hypertension and simultaneously introduced 1.5 gm/day MMF. CNI could be completely withdrawn in 41 cases. A total of 32 (75%) patients are currently on MMF. Mean follow-up from the introduction of MMF is 31.5 months and mean length of follow-up from the beginning of MMF monotherapy is 27.3 months. Renal function improved in 31/36 (89%) cases. Blood levels of cholesterol and triglycerides decreased in 13 of 17 (76%) and 15 of 17 (89%) patients, respectively. Arterial hypertension improved in 4 of 5 (80%) cases. A total of 8 patients showed a single episode of fluctuation of liver function tests during tapering off CNI. This feature was interpreted as an acute rejection (AR), based on the resolution of the clinical setting after escalation of MMF daily dose to 2 gm. A further patient developed a biopsy-proven AR insensitive to MMF adjustment, requiring reinstitution of the CNI dose. No deaths or major toxicity requiring MMF discontinuation occurred. In conclusion, low dose MMF monotherapy is safe, effective, and well tolerated.

  18. RENAL CRYOABLATION

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    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  19. Comparative study of the nutritional composition and toxic elements of farmed and wild Chanodichthys mongolicus

    Science.gov (United States)

    Jiang, Haifeng; Cheng, Xiaofei; Geng, Longwu; Tang, Shizhan; Tong, Guangxiang; Xu, Wei

    2017-07-01

    Information of the difference in quality between farmed and wild fish is central to better ensuring fish products produced in aquaculture meet regulatory and consumer requirements. Proximate composition, amino acid and fatty acid profiles, and toxic elements contents of farmed and wild Chanodichthys mongolicus were established and compared. Significantly higher crude protein content while lower moisture content in farmed fish compared to wild fish were observed ( Pcontent compared to wild counterpart ( Pelement levels (As, Cd, Pb and Hg) in comparison with wild fish, and both were far lower than the established limit standard. In conclusion, our results suggest that the nutritional quality of farmed C. mongolicus was inferior to their wild counterpart with respect to fatty acids nutrition, and therefore further studies should focus on the improving C. mongolicus diet in order to enhance the overall nutritional composition.

  20. Comparative analysis of renal flow using contrast power Doppler and gray-scale ultrasound

    Science.gov (United States)

    Sehgal, Chandra M.; Arger, Peter H.; Bovee, Kenneth C.; Pugh, Charles; Kirchhofer, Justin I.

    1997-05-01

    Our previous studies have shown that renal perfusion can be visualized by imaging the transit of a contrast agent through the parenchyma of the organ using gray scale (GS) and power Doppler (PD) ultrasound.However, the relative merits and the sensitivities of the two imaging methods are not known. This study compares the effectiveness of the two modes in visualizing kidney perfusion at the clinical dose of contrast agents. GS and PD images of the dog kidneys were recorded using a clinical ultrasound scanner at 4-7 MHz. A fixed longitudinal plane of the kidney was imaged by mounting the transducer on the animal with a specially designed holder. A dose of 0.1 m1/kg of Echogen was injected intravenously and GS and PD images were recorded simultaneously on two separate time-encoded video tapes during the passage of the contrast agent through the kidneys. The enhancement of GS and PD images was assessed qualitatively by three radiologists. The quantitative assessment was made by measuring the regional and global enhancements of digitized B-scan and PS images. Regional measurements were made by comparing brightness of the post contrast images with that of a pre-contrast reference image pixel by pixel. Student t-test was used to determine the statistical significance of the change. The regions representing statistically significant differences were encoded on the image in color with brightness proportional to the magnitude of change. The regions with no significant change were represented in GS. This generated a series of new images, referred to as StatMap, with color representing regions of perfusion. Changes in power Doppler images were visually detectable with high confidence in all five dogs by al three radiologists. There was no perceptible changes in B-scans. Computer analysis of PD images yielded characteristic indicator dilution curves in all five dogs with an initial rise time of 2-5 sec and a peak at 7-20 sec. The enhancement in PD lasted for 97-400 seconds. The

  1. Editor's Highlight: Comparative Renal Safety Assessment of the Hepatitis B Drugs, Adefovir, Tenofovir, Telbivudine and Entecavir in Rats.

    Science.gov (United States)

    Uteng, Marianne; Mahl, Andreas; Beckmann, Nicolau; Piaia, Alessandro; Ledieu, David; Dubost, Valerie; Tritto, Elaine; Wolf, Armin; Moulin, Pierre; Li, Li; Chibout, Salah-Dine; Pognan, Francois

    2017-01-01

    The aim of this study was to determine the relative safety of 4 antiviral drugs (telbivudine, tenofovir, adefovir, and entecavir) against hepatitis B virus with respect to kidney function and toxicity in male Sprague Dawley rats. The antiviral drugs were administered once daily for 4 weeks by oral gavage at ∼10 and 25-40 times the human equivalent dose. Main assessments included markers of renal toxicity in urine, magnetic resonance imaging (MRI) of kidney function, histopathology, and electron microscopic examination. Administration of adefovir at 11 and 28 mg/kg for 4 weeks caused functional and morphological kidney alterations in a time- and dose-dependent manner, affecting mainly the proximal tubules and suggesting a mechanism of toxicity related to mitochondrial degeneration/depletion. Of note, the observed adefovir-induced reduction of kidney function was not detected by the standard method of glomerular filtration rate (GFR) measurements (clearance rate of the endogenous marker, creatinine), thereby emphasizing the superiority of MRI in terms of sensitive detection of GFR in rats. For the low dose of 300 mg/kg of tenofovir, minor kidney effects such as nuclear enlargement in the tubular epithelium, and hyaline droplets accumulation were detected, which was also observed for the low dose (11 mg/kg) of adefovir. No assessments could be done at the higher dose of 600/1000 mg/kg tenofovir due to gastrointestinal tract toxicity which prevented treatment of the animals for longer than 1 week. Entecavir at 1 and 3 mg/kg and telbivudine at 600 and 1600 mg/kg caused no toxicologically relevant effects on the kidney. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Comparative metabolism, covalent binding and toxicity of BHT congeners in rat liver slices.

    Science.gov (United States)

    Reed, M; Fujiwara, H; Thompson, D C

    2001-11-28

    The metabolism, covalent binding and hepatotoxicity of butylated hydroxytoluene (BHT, 4-methyl-2,6-di-t-butylphenol) and two congeners (E-BHT, 4-ethyl-2,6-di-t-butylphenol; I-BHT, 4-isopropyl-2,6-di-t-butylphenol) were compared using precision-cut liver slices prepared from phenobarbital (PB)-treated male Sprague-Dawley rats. At equimolar concentrations (1 mM) BHT was the most toxic of the three compounds, causing an 80% decrease in cell viability over a 6 h incubation period. E-BHT was intermediate in toxicity while the isopropyl derivative was relatively nontoxic. Intracellular glutathione levels decreased prior to the onset of cytotoxicity. The cytochrome P450 inhibitor metyrapone completely inhibited the toxicity of all three compounds. The rates of metabolism of the three compounds to glutathione conjugates were compared in both PB-treated microsomes and PB-induced liver slices. In both models, the rate of formation was greatest for BHT, followed by E-BHT and I-BHT. Synthetic quinone methides (QMs) were prepared from each parent phenol and the rates of reactivity with three nucleophiles (water, methanol and glutathione) were compared. With each nucleophile, BHTQM was the most reactive, while I-BHTQM was the least reactive. Finally, covalent binding to protein was assessed in two ways. First, alkylation of an isolated model protein (bovine insulin) was measured in a microsomal enzyme activation system by mass spectrometry. Incubations with BHT produced the greatest extent of protein alkylation, followed by E-BHT, while no alkylation was observed with I-BHT. In the second system, covalent binding to cellular protein was assessed in rat liver PB microsomes and tissue slices by Western blotting using an antibody specific for the tert-butylphenol portion of the compounds. Binding was greatest for BHT, intermediate for E-BHT and could not be detected for I-BHT. The alkylation pattern for E-BHT was strikingly similar to that of BHT, suggesting that both compounds

  3. Comparative study of the effects of pyridoxine, rifampin, and renal function on hematological adverse events induced by linezolid.

    Science.gov (United States)

    Soriano, Alex; Ortega, Mar; García, Sebastián; Peñarroja, Georgina; Bové, Albert; Marcos, Miguel; Martínez, Juan C; Martínez, José A; Mensa, Josep

    2007-07-01

    Hematological disturbances that develop during linezolid treatment are a major concern when linezolid is administered for prolonged periods of time. The aim of this study was to evaluate the influences of pyridoxine, rifampin, and renal function on hematological adverse events. From January 2002 to April 2006, 52 patients received a long-term course of linezolid. Blood cell counts were monitored weekly. Thrombocytopenia was defined as a decrease to or =2 g/liter from the baseline value. Twenty-four patients received linezolid alone, and 28 patients received linezolid plus 200 mg of pyridoxine. The Kaplan-Meier survival method, followed by the log-rank test, was used to estimate the cumulative probability of adverse events, and Cox regression analysis was performed to evaluate the independent predictors of toxicity. The baseline characteristics of the patients in both groups were similar. The cumulative probability of thrombocytopenia and anemia in patients who received pyridoxine was not different from that in patients who did not receive it. Hematological adverse events were less frequent in patients taking rifampin and were more frequent in patients with renal failure. However; the Cox regression analysis showed that rifampin was the only independent predictor associated with a lower risk of thrombocytopenia (hazard ratio, 0.37; 95% confidence interval, 0.14 to 0.98; P = 0.045). In conclusion, pyridoxine did not prevent linezolid-related hematological adverse events, and the coadministration of rifampin was associated with a lower risk of thrombocytopenia.

  4. Increased risk of dialysis and end-stage renal disease among HIV patients in Denmark compared with the background population

    DEFF Research Database (Denmark)

    Rasch, Magnus G; Helleberg, Marie; Feldt-Rasmussen, Bo

    2014-01-01

    BACKGROUND: HIV patients have increased risk of impaired renal function. We aimed to estimate the incidence of any renal replacement therapy (aRRT) and start of chronic renal replacement therapy (cRRT) among HIV patients compared with population controls. METHODS: In a nationwide, population......-based cohort study we analysed incidence rates (IR), incidence rate ratios (IRR) and risk factors for aRRT and cRRT among HIV patients compared with an age- and gender-matched population control cohort using Poisson regression. RESULTS: We identified 5300 HIV patients and 53 000 population controls. The IRs...... per 10 000 person-years of aRRT and cRRT among HIV patients were 15.9 (95% CI: 12.5-20.1) and 4.4 (95% CI: 2.8-6.9), respectively. The IRR was 4.7 (95% CI: 3.5-6.2) for aRRT and 3.6 (95% CI: 2.2-6.0) for cRRT compared with population controls. Risk of aRRT was increased during the first year after HIV...

  5. Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats

    Directory of Open Access Journals (Sweden)

    Lee IC

    2016-06-01

    Full Text Available In-Chul Lee,1 Je-Won Ko,1 Sung-Hyeuk Park,1 Je-Oh Lim,1 In-Sik Shin,1 Changjong Moon,1 Sung-Hwan Kim,2 Jeong-Doo Heo,3 Jong-Choon Kim1 1College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, 2Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, 3Gyeongnam Department of Environment and Toxicology, Korea Institute of Toxicology, Gyeongnam, Republic of Korea Abstract: Despite widespread use and prospective biomedical applications of copper nanoparticles (Cu NPs, their biosafety issues and kinetics remain unclear. Thus, the aim of this study was to compare the detailed in vivo toxicity of Cu NPs and cupric ions (CuCl2; Cu ions after a single oral dose. We determined the physicochemical characteristics of Cu NPs, including morphology, hydrodynamic size, zeta potential, and dissolution in gastric (pH 1.5, vehicle (pH 6.5, and intestinal (pH 7.8 conditions. We also evaluated the kinetics of Cu following a single equivalent dose (500 mg/kg of Cu NPs and Cu ions. Cu NPs had highest dissolution (84.5% only in gastric conditions when compared with complete dissolution of Cu ions under various physiological milieus. Kinetic analysis revealed that highest Cu levels in blood and tested organs of Cu NP-treated rats were 15%–25% lower than that of Cu ions. Similar to the case of Cu ions, Cu levels in the tested organs (especially liver, kidney, and spleen of Cu NP-treated rats increased significantly when compared with the vehicle control. However, delay in reaching the highest level and biopersistence of Cu were observed in the blood and tested organs of Cu NP-treated rats compared with Cu ions. Extremely high levels of Cu in feces indicated that unabsorbed Cu NPs or absorbed Cu ions were predominantly eliminated through liver/feces. Cu NPs exerted apparent toxicological effects at higher dose levels compared with Cu ions and showed sex-dependent differences in mortality, biochemistry, and

  6. Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP

    Directory of Open Access Journals (Sweden)

    Diego A. Fernández

    2014-01-01

    Full Text Available Okadaic acid (OA and its analogues, dinophysistoxin 1 (DTX1 and dinophysistoxin 2 (DTX2, are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2–10 times higher than the intraperitoneal (i.p. lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.

  7. Experimental basis for the high oral toxicity of dinophysistoxin 1: a comparative study of DSP.

    Science.gov (United States)

    Fernández, Diego A; Louzao, M Carmen; Fraga, María; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

    2014-01-03

    Okadaic acid (OA) and its analogues, dinophysistoxin 1 (DTX1) and dinophysistoxin 2 (DTX2), are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP) in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2-10 times higher than the intraperitoneal (i.p.) lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.

  8. Comparative toxicity of Paraquat herbicide and some plant extracts in Lymnaea natalensis snails.

    Science.gov (United States)

    Bakry, Fayez A; Eleiwa, Mona E; Taha, Samir A; Ismil, Somya M

    2016-01-01

    Paraquat has been shown to be a highly toxic compound for humans and animals, and many cases of acute poisoning and death have been reported over the past few decades. The present study was undertaken to evaluate comprehensively herbicides (Paraquat) and some plant extracts to biochemical aspects of Lymnaea natalensis snails. It was found that the exposure of L. natalensis to Paraquat and plant extracts led to a significant reduction in the infectivity of Fasciola gigantica miracidia to the snail. The glucose level in hemolymph of exposed snails was elevated, while the glycogen showed a decrease in soft tissues when compared with the control group. In addition, the activity level of some enzymes representing glycolytic enzymes as hexokinase (HK), pyruvate kinase (PK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), and glucose phosphate isomerase (GPI) in snail's tissues were reduced in response to the treatment. It was concluded that the pollution of the aquatic environment by herbicide would adversely affect the metabolism of the L. natalensis snails. Snails treated with Agave attenuate, Ammi visnaga, and Canna iridiflora plant had less toxic effect compared to snails treated with Paraquat.

  9. Comparative respiratory toxicity of particles produced by traffic and sugar cane burning.

    Science.gov (United States)

    Mazzoli-Rocha, Flavia; Magalhães, Clarissa Bichara; Malm, Olaf; Saldiva, Paulo Hilário Nascimento; Zin, Walter Araujo; Faffe, Débora Souza

    2008-09-01

    The impact of particle emissions by biomass burning is increasing throughout the world. We explored the toxicity of particulate matter produced by sugar cane burning and compared these effects with equivalent mass of traffic-derived particles. For this purpose, BALB/c mice received a single intranasal instillation of either distilled water (C) or total suspended particles (15 microg) from an urban area (SP group) or biomass burning-derived particles (Bio group). Lung mechanical parameters (total, resistive and viscoelastic pressures, static elastance, and elastic component of viscoelasticity) and histology were analyzed 24h after instillation. Trace elements and polycyclic aromatic hydrocarbons (PAHs) metabolites of the two sources of particles were determined. All mechanical parameters increased similarly in both pollution groups compared with control, except airway resistive pressure, which increased only in Bio. Both exposed groups showed significantly higher fraction area of alveolar collapse, and influx of polymorphonuclear cells in lung parenchyma than C. The composition analysis of total suspended particles showed higher concentrations of PAHs and lower concentration of metals in traffic than in biomass burning-derived particles. In conclusion, we demonstrated that a single low dose of ambient particles, produced by traffic and sugar cane burning, induced significant alterations in pulmonary mechanics and lung histology in mice. Parenchymal changes were similar after exposure to both particle sources, whereas airway mechanics was more affected by biomass-derived particles. Our results indicate that biomass particles were at least as toxic as those produced by traffic.

  10. Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats.

    Science.gov (United States)

    Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Lim, Je-Oh; Shin, In-Sik; Moon, Changjong; Kim, Sung-Hwan; Heo, Jeong-Doo; Kim, Jong-Choon

    2016-01-01

    Despite widespread use and prospective biomedical applications of copper nanoparticles (Cu NPs), their biosafety issues and kinetics remain unclear. Thus, the aim of this study was to compare the detailed in vivo toxicity of Cu NPs and cupric ions (CuCl2; Cu ions) after a single oral dose. We determined the physicochemical characteristics of Cu NPs, including morphology, hydrodynamic size, zeta potential, and dissolution in gastric (pH 1.5), vehicle (pH 6.5), and intestinal (pH 7.8) conditions. We also evaluated the kinetics of Cu following a single equivalent dose (500 mg/kg) of Cu NPs and Cu ions. Cu NPs had highest dissolution (84.5%) only in gastric conditions when compared with complete dissolution of Cu ions under various physiological milieus. Kinetic analysis revealed that highest Cu levels in blood and tested organs of Cu NP-treated rats were 15%-25% lower than that of Cu ions. Similar to the case of Cu ions, Cu levels in the tested organs (especially liver, kidney, and spleen) of Cu NP-treated rats increased significantly when compared with the vehicle control. However, delay in reaching the highest level and biopersistence of Cu were observed in the blood and tested organs of Cu NP-treated rats compared with Cu ions. Extremely high levels of Cu in feces indicated that unabsorbed Cu NPs or absorbed Cu ions were predominantly eliminated through liver/feces. Cu NPs exerted apparent toxicological effects at higher dose levels compared with Cu ions and showed sex-dependent differences in mortality, biochemistry, and histopathology. Liver, kidney, and spleen were the major organs affected by Cu NPs. Collectively, the toxicity and kinetics of Cu NPs are most likely influenced by the release of Cu dissociated from Cu NPs under physiological conditions.

  11. Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles.

    Science.gov (United States)

    Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Shin, Na-Rae; Shin, In-Sik; Moon, Changjong; Kim, Je-Hein; Kim, Hyoung-Chin; Kim, Jong-Choon

    2016-10-28

    Copper nanoparticles (Cu NPs) have great potential in electronics and biomedical fields because of their efficient thermodynamic and anti-microbial properties. However, their potential toxic effects and kinetic data following repeated exposure are still unclear. We evaluated the physicochemical properties of Cu NPs (25 nm) and copper microparticles (Cu MPs, 14-25 μm). Comparative in vivo toxicity of Cu NPs and Cu MPs was evaluated by conducting a 28-day repeated oral dose study at equivalent dose levels of 0, 100, 200, and 400 mg/kg/day (vehicle, 1 % hydroxypropyl methylcellulose). We determined Cu levels in the blood, tissues, urine, and feces by using inductively coupled plasma mass spectrometry. The solubility of Cu NPs and Cu MPs was 84.5 and 17.2 %, respectively, in an acidic milieu; however, they scarcely dissolved in vehicle or intestinal milieus. The specific surface area of Cu NPs and Cu MPs was determined to be 14.7 and 0.16 m(2)/g, respectively. Cu NPs exhibited a dose-dependent increase of Cu content in the blood and tested organs, with particularly high levels of Cu in the liver, kidney, and spleen. Only for liver and kidney increased Cu levels were found in Cu MPs-treated rats. Cu NPs caused a dose-related increase in Cu levels in urine, whereas Cu MPs did not affect the urine Cu levels. Extremely high levels of Cu were detected in the feces of Cu MPs-treated rats, whereas much lower levels were detected in the feces of Cu NPs-treated rats. A comparative in vivo toxicity study showed that Cu NPs caused damages to red blood cells, thymus, spleen, liver, and kidney at ≥200 mg/kg/days, but Cu MPs did not cause any adverse effects even at the highest dose. Overall, the in vivo repeated dose toxicity study of Cu NPs and Cu MPs demonstrated that large surface area and high solubility in physiological milieus could directly influence the toxicological responses and biodistribution of Cu particles when administered orally. Under these experimental

  12. No change in complication rate using spring-loaded gun compared to traditional percutaneous renal allograft biopsy techniques.

    Science.gov (United States)

    Kovalik, E C; Schwab, S J; Gunnells, J C; Bowie, D; Smith, S R

    1996-06-01

    The previous methods to biopsy renal allografts at our institution involved the use of the Franklin-Silverman or Tru-Cut needles. Unfortunately they had a significant rate of post biopsy bleeding secondary to deep penetration when excess force was used to penetrate a tough transplant capsule. Although spring loaded biopsy devices have been widely used for native kidney biopsies over the past three years, the complication rate for renal allograft biopsies has not been sufficiently evaluated. We describe our experience using a disposable spring loaded biopsy device on transplanted renal grafts. Fifty-four biopsies were performed with the device, all under ultrasound guidance. The ASAP automatic biopsy system by Medi-tech was used comprising of a spring loaded gun with a 15 cm long 15 GA needle echogenic tip and 17 mm specimen notch. All patients were ultrasounded immediately post biopsy to look for hematomas. Compared to 55 previous biopsies performed using Tru-Cut needles, we conclude that the ASAP automated biopsy system proved equally effective in obtaining adequate tissue for diagnosis with fewer post-biopsy hematomas compared to traditional biopsy methods.

  13. Comparative study of multiport laparoscopy and umbilical laparoendoscopic single-site surgery with reusable platform for treating renal masses.

    Science.gov (United States)

    Chantada, C; García-Tello, A; Esquinas, C; Moraga, A; Redondo, C; Angulo, J C

    Umbilical laparoendoscopic single-site (LESS) surgery is an increasingly used modality for treating renal masses. We present a prospective comparison between LESS renal surgery and conventional laparoscopy. A comparative paired study was conducted that evaluated the surgical results and complications of patients with renal neoplasia treated with LESS surgery (n=49) or multiport laparoscopy (n=53). The LESS approach was performed with reusable material placed in the navel and double-rotation curved instruments. An additional 3.5-mm port was employed in 69.4% of the cases. We assessed demographic data, the type of technique (nephrectomy, partial nephrectomy and nephroureterectomy), surgical time, blood loss, haemoglobin, need for transfusion, number and severity of complications (Clavien-Dindo), hospital stay, histological data and prognosis. There were no differences in follow-up, age, sex, body mass index, preoperative haemoglobin levels or type of surgery. Conversion occurred in 2 cases (1 in each group). The surgical time was equivalent (P=.6). Intraoperative transfusion (P=.03) and blood loss (Pmasses, with time consumption and safety comparable to conventional laparoscopy. The LESS approach is advantageous in terms of blood loss and hospital stay. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Exxon Valdez to Deepwater Horizon: comparable toxicity of both crude oils to fish early life stages.

    Science.gov (United States)

    Incardona, John P; Swarts, Tanya L; Edmunds, Richard C; Linbo, Tiffany L; Aquilina-Beck, Allisan; Sloan, Catherine A; Gardner, Luke D; Block, Barbara A; Scholz, Nathaniel L

    2013-10-15

    The 2010 Deepwater Horizon disaster in the Gulf of Mexico was the largest oil spill in United States history. Crude oils are highly toxic to developing fish embryos, and many pelagic fish species were spawning in the northern Gulf in the months before containment of the damaged Mississippi Canyon 252 (MC252) wellhead (April-July). The largest prior U.S. spill was the 1989 grounding of the Exxon Valdez that released 11 million gallons of Alaska North Slope crude oil (ANSCO) into Prince William Sound. Numerous studies in the aftermath of the Exxon Valdez spill defined a conventional crude oil injury phenotype in fish early life stages, mediated primarily by toxicity to the developing heart. To determine whether this type of injury extends to fishes exposed to crude oil from the Deepwater Horizon - MC252 incident, we used zebrafish to compare the embryotoxicity of ANSCO alongside unweathered and weathered MC252 oil. We also developed a standardized protocol for generating dispersed oil water-accommodated fractions containing microdroplets of crude oil in the size range of those detected in subsurface plumes in the Gulf. We show here that MC252 oil and ANSCO cause similar cardiotoxicity and photo-induced toxicity in zebrafish embryos. Morphological defects and patterns of cytochrome P450 induction were largely indistinguishable and generally correlated with polycyclic aromatic compound (PAC) composition of each oil type. Analyses of embryos exposed during different developmental windows provided additional insight into mechanisms of crude oil cardiotoxicity. These findings indicate that the impacts of MC252 crude oil on fish embryos and larvae are consistent with the canonical ANSCO cardiac injury phenotype. For those marine fish species that spawned in the northern Gulf of Mexico during and after the Deepwater Horizon incident, the established literature can therefore inform the assessment of natural resource injury in the form of potential year-class losses.

  15. Comparative Study for the Effect of Tamsulosin on Biomarkers between Renal and Urethral Stone Lithotripsy

    Directory of Open Access Journals (Sweden)

    Mohammed Khalid Abood

    2015-10-01

    Full Text Available Nephrolithiasis are multi-factorial diseases that result from the combined influence of epidemiological, biochemical and genetically risk factors. Defective drainage due to urinary tract obstruction at the narrowest part (ureterovesical junction, ureteropelvic junction, and near the pelvic brim via stones will eventually cause the agonizing renal colic pain. Therapeutic managements of nephrolithiasis to relief acute colic pain are the primary objective. Non-steroidal anti-inflammatory drugs are the most commonly used drugs as suggested by many studies. It is very important to consider side effects of the drugs used in the treatment of colic pain. In order to preserve renal function and to relief obstruction, medical expulsion therapy are used for urethral calculi as a conservative management. These medications will aid the passage urethral calculi, an area that currently seems to be a field for continuous investigation.

  16. Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in renal transplantation: 2 year follow-up results.

    Science.gov (United States)

    Krämer, Bernhard K; Montagnino, Giuseppe; Del Castillo, Domingo; Margreiter, Raimund; Sperschneider, Heide; Olbricht, Christoph J; Krüger, Bernd; Ortuño, Joaquín; Köhler, Hans; Kunzendorf, Ulrich; Stummvoll, Hans-Krister; Tabernero, Jose M; Mühlbacher, Ferdinand; Rivero, Manuel; Arias, Manuel

    2005-05-01

    Comparison studies of calcineurin inhibitors as cornerstone immunosuppressants in renal transplantation have demonstrated that tacrolimus consistently reduces acute rejection rates and, in some studies, also improves long-term renal outcome in comparison to cyclosporin A (CsA). The aim of the present 2 year follow-up of the European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was to investigate long-term clinical outcome in terms of rate of acute rejection, graft and patient survival and graft function. The European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was a randomized, comparative 6 month trial of the calcineurin inhibitors tacrolimus and CsA in combination with both azathioprine and steroids. The intent-to-treat population (ITT) consisted of 286 patients in the tacrolimus arm and 271 in the CsA microemulsion (CsA-ME) arm. Whereas whole blood level targets were 10-20 and 5-15 ng/ml for tacrolimus and 100-400 and 100-200 ng/ml for CsA during months 0-3 and 4-6, respectively, during the investigator-driven follow-up after termination of the main study (months 7-24) no specific calcineurin inhibitor target levels were required. Follow-up data were collected at 2 years post-transplantation from 237 (82.9% of the ITT population) patients who received tacrolimus and 222 (81.9% of the ITT population) patients who received CsA-ME. Calculated on ITT populations, mortality (2.0% vs 3.3%; PRenal function 2 years post-transplant, measured by serum creatinine concentrations, was significantly better in tacrolimus-based compared with CsA-ME-based immunosuppression (136.9 vs 161.6 micromol/l; Ptransplantation. Tacrolimus-based immunosuppression may induce long-term benefits with regard to graft function and graft survival. The overall side-effect profile is considered to be favourable.

  17. Comparative toxicity of chlorpyrifos and its oxon derivatives to soil microbial activity by combined methods.

    Science.gov (United States)

    Wang, Fei; Yao, Jun; Chen, Huilun; Chen, Ke; Trebse, Polonca; Zaray, Gyula

    2010-01-01

    The inhibitory effects of the pesticide Chlorpyrifos (CPF) and its oxon derivative (CPO) on soil microbial activity were evaluated through the measurement of metabolic parameters and the microbial urease enzyme. The thermodynamic parameters related to microbial activity were measured and recorded as power-time curves. Microbial growth rate constant k, total heat evolution Q(T), metabolic enthalpy DeltaH(met), mass specific heat rate J(Q/S), microbial biomass C and inhibitory ratio I were calculated. They showed the linear relationship with doses of CPF and CPO. Thereinto, the linear correlations, k versus biomass C and DeltaH(met) versus biomass C, elucidated that k and DeltaH(met) were growth yield dependent. In this work, 20% inhibitory ratio IC(20) was obtained with 9.8 microg g(-1) for CPF and 0.37 microg g(-1) CPO, meaning that the acute toxicity of CPO was 26 times that of CPF, since the CPO had more potent toxicity to living organism due to its active functional group. Comparing the change tendency of DeltaH(met) and other parameter, the values almost kept constant when exposure to CPF (<5.0 microg g(-1)). It illustrates that individual reacted to stress resulted from environment change by shifting resources from other biological activities (such as reproduction or growth) toward survival to some extent. Urease activity responses in relation to the CPF and CPO exposure were observed and consistent with above thermodynamic parameters.

  18. Comparative toxicity of pyrethroid insecticides to two estuarine crustacean species, Americamysis bahia and Palaemonetes pugio.

    Science.gov (United States)

    DeLorenzo, Marie E; Key, Peter B; Chung, Katy W; Sapozhnikova, Yelena; Fulton, Michael H

    2014-10-01

    Pyrethroid insecticides are widely used on agricultural crops, as well as for nurseries, golf courses, urban structural and landscaping sites, residential home and garden pest control, and mosquito abatement. Evaluation of sensitive marine and estuarine species is essential for the development of toxicity testing and risk-assessment protocols. Two estuarine crustacean species, Americamysis bahia (mysids) and Palaemonetes pugio (grass shrimp), were tested with the commonly used pyrethroid compounds, lambda-cyhalothrin, permethrin, cypermethrin, deltamethrin, and phenothrin. Sensitivities of adult and larval grass shrimp and 7-day-old mysids were compared using standard 96-h LC50 bioassay protocols. Adult and larval grass shrimp were more sensitive than the mysids to all the pyrethroids tested. Larval grass shrimp were approximately 18-fold more sensitive to lambda-cyhalothrin than the mysids. Larval grass shrimp were similar in sensitivity to adult grass shrimp for cypermethrin, deltamethrin, and phenothrin, but larvae were approximately twice as sensitive to lambda-cyhalothrin and permethrin as adult shrimp. Acute toxicity to estuarine crustaceans occurred at low nanogram per liter concentrations of some pyrethroids, illustrating the need for careful regulation of the use of pyrethroid compounds in the coastal zone. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

  19. The impact of floc size on respiration inhibition by soluble toxicants--a comparative investigation.

    Science.gov (United States)

    Henriques, Inês D S; Holbrook, R David; Kelly, Richard T; Love, Nancy G

    2005-07-01

    Activated sludge facilities are susceptible to upset by shock loads of toxic compounds. We hypothesized that floc size plays an important role in determining the sensitivity of mixed liquor to shock by cadmium and 2,4-dinitrophenol (DNP). To test this hypothesis, heterotrophic respiration inhibition experiments were conducted using mixed liquor from a pilot-scale membrane bioreactor (MBR) and full-scale activated sludge (FSAS) facility with gravity settling secondary clarifiers that were operated under similar process conditions. MBR mixed liquor flocs were both 41% smaller and 2 and 1.25 times more sensitive to equivalent soluble cadmium and DNP concentrations, respectively, compared to FSAS mixed liquor flocs. Similarly, FSAS mixed liquor that had been sheared (resulting in a smaller average floc diameter) was 1.5 times more sensitive to soluble cadmium than non-sheared FSAS mixed liquor. These results suggest that activated sludge process conditions that create smaller floc particles, such as the use of membranes for liquid-solid separation, are more susceptible to upset events caused by shock loads of cadmium and DNP. The particle size distribution (PSD) and average floc diameter of a mixed liquor suspension should be measured and reported when stating the inhibition concentration of a specific toxicant.

  20. A comparative study about toxicity of CdSe quantum dots on reproductive system development of mice and controlling this toxicity by ZnS coverage

    Directory of Open Access Journals (Sweden)

    Akram Valipoor

    2015-10-01

    Full Text Available Objective(s:Medicinal benefits of quantum dots have been proved in recent years but there is little known about their toxicity especially in vivo toxicity. In order to use quantum dots in medical applications, studies ontheir in vivo toxicity is important. Materials and Methods: CdSe:ZnS quantum dots were injected in 10, 20, and 40 mg/kg doses to male mice10 days later, mice were sacrificed and five micron slides were prepared structural and optical properties of quantum dots were evaluated using XRD. Results:  Histological studies of testis tissue showed high toxic effect of CdSe:ZnS  in 40 mg/kg group. Histological studies of epididymis did not show any effect of quantum dots in terms of morphology and tube structure. Mean concentration of LH and testosterone and testis weight showed considerable changes in mice injected with 40 mg/kg dose of CdSe:ZnS compared to control group. However, FSH and body weight did not show any difference with control group. Conclusion: Although it has been reported that CdSe is highly protected from the environment by its shell, but  this study showed high toxicity for CdSe:ZnS when it is used in vivo which could be suggested that shell could contribute to increased toxicity of quantum dots. Considering lack of any previous study on this subject, our study could potentially be used as an basis for further extensive studies investigating the effects of quantum dots toxicity on development of male sexual system.

  1. Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study

    Directory of Open Access Journals (Sweden)

    Boulware Ebony L

    2012-12-01

    Full Text Available Abstract Background Evidence is lacking to inform providers’ and patients’ decisions about many common treatment strategies for patients with end stage renal disease (ESRD. Methods/design The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US Agency for Health Care Research and Quality to study the comparative effectiveness of: 1 antihypertensive therapies, 2 early versus later initiation of dialysis, and 3 intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1 the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009, (2 the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003–2010 with complete outcome ascertainment through 2010, (3 the United States Renal Data System (333,308 incident dialysis patients from 2006–2009 with complete outcome ascertainment through 2010, and (4 the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009. We ascertain patient reported outcomes (i.e., health-related quality of life, morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. Discussion The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the

  2. Development of Comparative Toxicity Potentials of 14 cationic metals in freshwater

    DEFF Research Database (Denmark)

    Dong, Yan; Gandhi, Nilima; Hauschild, Michael Zwicky

    2014-01-01

    Site-dependent and site-generic Comparative Toxicity Potentials (CTPs) (also known as Characterization Factors (CFs)) were calculated for 14 cationic metals (Al(III), Ba, Be, Cd, Co, Cr(III), Cs, Cu(II), Fe(II), Fe(III), Mn(II), Ni, Pb, Sr and Zn), to be applied in Life Cycle Impact Assessment....... CTPs were calculated for 7 EUarchetypes, taking bioavailability and speciation pattern into account. The resulting site-dependent CTPs showed up to 2.4–6.5 orders of magnitude variation across archetypes for those metals that form stable hydroxyl compounds in slightly alkaline waters (Al(III), Be, Cr......(III), Cu(II) and Fe(III)), emphasizing the importance of using site-dependent CTPs for these metals where possible. For the other metals, CTPs stayed within around 0.9 orders of magnitude, making spatial differentiation less important. In acidic waters (pH

  3. Comparative toxicity of oxygenated monoterpenoids in experimental hydroalcoholic lotions to permethrin-resistant adult head lice.

    Science.gov (United States)

    Gonzalez-Audino, Paola; Picollo, María Inés; Gallardo, Anabella; Toloza, Ariel; Vassena, Claudia; Mougabure-Cueto, Gastón

    2011-07-01

    The use of botanical compounds such as essential oils has recently become the subject of great interest as a natural means of pest control because of their ovicidal, larvicidal, or adulticidal activity against various insect species including head lice. We tested and compared the efficacy of pure oxygenated monoterpenoids that are main ingredients of essential oils of good biological activity. We used pulegone and citral, components of Aloysia citrodora, and geraniol, citronellol, and linalool, components of Geranium sp. oil. We found that citronellol and geraniol showed the highest knockdown and mortality effect (>60%) on adults of both sexes (50:50%) and third-stage nymphs. Pulegone, linalool, and citral showed knockdown percentages between 42 and 55%, and mortality percentages between 47 and 53%. A simple linear regression analysis showed statistically significant relationships between the studied toxic effects and viscosity of the monoterpenoids (p < 0.05), but not with their partition coefficient (log P).

  4. Comparative imaging study in ultrasound, MRI, CT, and DSA using a multimodality renal artery phantom

    Energy Technology Data Exchange (ETDEWEB)

    King, Deirdre M.; Fagan, Andrew J.; Moran, Carmel M.; Browne, Jacinta E. [Medical Ultrasound Physics and Technology Group, School of Physics, Dublin Institute of Technology, Dublin 8 (Ireland); Centre for Advanced Medical Imaging (CAMI), St James' s Hospital, Dublin 8 (Ireland); Department of Medical Physics, University of Edinburgh, Edinburgh EH16 4TJ (United Kingdom); Medical Ultrasound Physics and Technology Group, School of Physics, Dublin Institute of Technology, Dublin 8 (Ireland)

    2011-02-15

    Purpose: A range of anatomically realistic multimodality renal artery phantoms consisting of vessels with varying degrees of stenosis was developed and evaluated using four imaging techniques currently used to detect renal artery stenosis (RAS). The spatial resolution required to visualize vascular geometry and the velocity detection performance required to adequately characterize blood flow in patients suffering from RAS are currently ill-defined, with the result that no one imaging modality has emerged as a gold standard technique for screening for this disease. Methods: The phantoms, which contained a range of stenosis values (0%, 30%, 50%, 70%, and 85%), were designed for use with ultrasound, magnetic resonance imaging, x-ray computed tomography, and x-ray digital subtraction angiography. The construction materials used were optimized with respect to their ultrasonic speed of sound and attenuation coefficient, MR relaxometry (T{sub 1},T{sub 2}) properties, and Hounsfield number/x-ray attenuation coefficient, with a design capable of tolerating high-pressure pulsatile flow. Fiducial targets, incorporated into the phantoms to allow for registration of images among modalities, were chosen to minimize geometric distortions. Results: High quality distortion-free images of the phantoms with good contrast between vessel lumen, fiducial markers, and background tissue to visualize all stenoses were obtained with each modality. Quantitative assessments of the grade of stenosis revealed significant discrepancies between modalities, with each underestimating the stenosis severity for the higher-stenosed phantoms (70% and 85%) by up to 14%, with the greatest discrepancy attributable to DSA. Conclusions: The design and construction of a range of anatomically realistic renal artery phantoms containing varying degrees of stenosis is described. Images obtained using the main four diagnostic techniques used to detect RAS were free from artifacts and exhibited adequate contrast

  5. Toxicity of sediments from lead-zinc mining areas to juvenile freshwater mussels (Lampsilis siliquoidea) compared to standard test organisms.

    Science.gov (United States)

    Besser, John M; Ingersoll, Christopher G; Brumbaugh, William G; Kemble, Nile E; May, Thomas W; Wang, Ning; MacDonald, Donald D; Roberts, Andrew D

    2015-03-01

    Sediment toxicity tests compared chronic effects on survival, growth, and biomass of juvenile freshwater mussels (28-d exposures with Lampsilis siliquoidea) to the responses of standard test organisms-amphipods (28-d exposures with Hyalella azteca) and midges (10-d exposures with Chironomus dilutus)-in sediments from 2 lead-zinc mining areas: the Tri-State Mining District and Southeast Missouri Mining District. Mussel tests were conducted in sediments sieved to toxic responses (reduced 10% or more relative to reference sites) in Tri-State sediments was greatest for amphipod survival (25% of samples), midge biomass (20%), and mussel survival (14%). In southeast Missouri sediments, the frequency of highly toxic samples was greatest for mussel biomass (25%) and amphipod biomass (13%). Thresholds for metal toxicity to mussels, expressed as hazard quotients based on probable effect concentrations, were lower for southeast Missouri sediments than for Tri-State sediments. Southeast Missouri sites with toxic sediments had 2 or fewer live mussel taxa in a concurrent mussel population survey, compared with 7 to 26 taxa at reference sites. These results demonstrate that sediment toxicity tests with juvenile mussels can be conducted reliably by modifying existing standard methods; that the sensitivity of mussels to metals can be similar to or greater than standard test organisms; and that responses of mussels in laboratory toxicity tests are consistent with effects on wild mussel populations.

  6. A pharmacologically-based array to identify targets of cyclosporine A-induced toxicity in cultured renal proximal tubule cells

    Energy Technology Data Exchange (ETDEWEB)

    Sarró, Eduard, E-mail: eduard.sarro@vhir.org [Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Jacobs-Cachá, Conxita, E-mail: conxita.jacobs@vhir.org [Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Itarte, Emilio, E-mail: emili.itarte@uab.es [Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Meseguer, Anna, E-mail: ana.meseguer@vhir.org [Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain)

    2012-01-15

    Mechanisms of cyclosporine A (CsA)-induced nephrotoxicity were generally thought to be hemodynamic in origin; however, there is now accumulating evidence of a direct tubular effect. Although genomic and proteomic experiments by our group and others provided overall information on genes and proteins up- or down-regulated by CsA in proximal tubule cells (PTC), a comprehensive view of events occurring after CsA exposure remains to be described. For this purpose, we applied a pharmacologic approach based on the use of known activities of a large panel of potentially protective compounds and evaluated their efficacy in preventing CsA toxicity in cultured mouse PTC. Our results show that compounds that blocked protein synthesis and apoptosis, together with the CK2 inhibitor DMAT and the PI3K inhibitor apigenin, were the most efficient in preventing CsA toxicity. We also identified GSK3, MMPs and PKC pathways as potential targets to prevent CsA damage. Additionally, heparinase-I and MAPK inhibitors afforded partial but significant protection. Interestingly, antioxidants and calcium metabolism-related compounds were unable to ameliorate CsA-induced cytotoxicity. Subsequent experiments allowed us to clarify the hierarchical relationship of targeted pathways after CsA treatment, with ER stress identified as an early effector of CsA toxicity, which leads to ROS generation, phenotypical changes and cell death. In summary, this work presents a novel experimental approach to characterizing cellular responses to cytotoxics while pointing to new targets to prevent CsA-induced toxicity in proximal tubule cells. Highlights: ► We used a novel pharmacological approach to elucidate cyclosporine (CsA) toxicity. ► The ability of a broad range of compounds to prevent CsA toxicity was evaluated. ► CsA toxicity was monitored using LDH release assay and PARP cleavage. ► Protein synthesis, PI3K, GSK3, MMP, PKC and caspase inhibitors prevented CsA toxicity. ► We also identified ER

  7. Histopathological study of the hepatic and renal toxicity associated with the co-administration of imatinib and acetaminophen in a preclinical mouse model.

    Science.gov (United States)

    Nassar, Inthisham; Pasupati, Thanikachalam; Judson, John Paul; Segarra, Ignacio

    2010-06-01

    Imatinib, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukaemia (CML) and gastrointestinal stromal tumors (GIST). Several fatal cases have been associated with imatinib hepatotoxicity. Acetaminophen, an over-the-counter analgesic, anti-pyretic drug, which can cause hepatotoxicity, is commonly used in cancer pain management. We assessed renal and hepatic toxicity after imatinib and acetaminophen co-administration in a preclinical model. Four groups of male ICR mice (30-35 g) were fasted overnight and administered either saline solution orally (baseline control), imatinib 100 mg/kg orally (control), acetaminophen 700 mg/kg intraperitoneally (positive control) or co-administered imatinib 100 mg/kg orally and acetaminophen 700 mg/kg intraperitoneally (study group), and sacrificed at 15 min, 30 min, 1 h, 2 h, 4 h and 6 h post-administration (n = 4 per time point). The liver and kidneys were harvested for histopathology assessment. The liver showed reversible cell damage like feathery degeneration, microvesicular fatty change, sinusoidal congestion and pyknosis, when imatinib or acetaminophen were administered separately. The damage increased gradually with time, peaked at 2 h but resolved by 4 h. When both drugs were administered concurrently, the liver showed irreversible damage (cytolysis, karyolysis and karyorrhexis) which did not resolve by 6 h. Very minor renal changes were observed. Acetaminophen and imatinib co-administration increased hepatoxicity which become irreversible, probably due to shared P450 biotransformation pathways and transporters in the liver.

  8. Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

    Energy Technology Data Exchange (ETDEWEB)

    McGuire, S.A.

    1991-02-01

    The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m{sup 3} for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m{sup 3} (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs.

  9. Comparative efficacy and toxic effects of carvacryl acetate and carvacrol on sheep gastrointestinal nematodes and mice.

    Science.gov (United States)

    Andre, Weibson P P; Ribeiro, Wesley L C; Cavalcante, Géssica S; dos Santos, Jessica M L; Macedo, Iara T F; de Paula, Haroldo C B; de Freitas, Rivelilson M; de Morais, Selene M; de Melo, Janaina V; Bevilaqua, Claudia M L

    2016-03-15

    Carvacrol is a compound isolated from some essential oils. It has been reported to possess anthelmintic activity. Acetylation of this monoterpene has been proposed as a potential way to reduce the toxicity and enhance the pharmacological effects of carvacrol. This study aimed to evaluate the effect of carvacryl acetate (CA) using in vitro and in vivo assays with gastrointestinal nematodes of small ruminants. The egg hatching test (EHT), larval development test (LDT) and adult worm motility (AWM) assessment were conducted to evaluate the effect of the acetylated product and pure carvacrol on Haemonchus contortus eggs, larvae and adults. The structural changes induced in adult H. contortus were assessed using scanning electron microscopy (SEM). CA and carvacrol acute toxicity was evaluated in mice. Finally, the efficacy of 250 mg/kg CA and 2.5mg/kg monepantel (positive control) were evaluated in 30 sheep naturally infected with gastrointestinal nematodes by the fecal egg count reduction test (FECRT). In vitro tests were analyzed by analysis of variance (ANOVA) followed by comparison with Tukey's test. The efficacy was calculated by the Boot Street program using the arithmetic average. The number of eggs in feces (epg) of the groups were transformed to log (x+1) and subjected to ANOVA to compare differences among the groups by Tukey's test. The level of significance was P<0.05. CA and carvacrol inhibited larval hatching by 89.3 and 97.7% at doses of 8.0 and 1.0mg/ml, respectively. At the concentration of 2mg/ml, CA and carvacrol inhibited 100% of larval development. At a concentration of 200 μg/ml, CA and carvacrol inhibited the motility of adult worms by 100% and 58.3% at 24h post-exposure, respectively. CA caused cuticle and vulvar flap wrinkling and bubbles to emerge from the tegument. Carvacrol caused more discreet effects on the cuticle and vulvar flap. The LD10 and LD50 of CA were 566.7 mg/kg and 1544.5mg/kg, respectively. The LD10 and LD50 of carvacrol were

  10. Efficacy of anti-pruritis drugs in chronic renal failure: a comparative study

    Directory of Open Access Journals (Sweden)

    "H. Khalili

    2006-07-01

    Full Text Available Background: Pruritus is one of the most common problems in patients suffering chronic renal failure. Twenty five - 35% of predialysis patients and 60-80% of patients during dialysis complain pruritus. The exact pathophysiology of pruritus is unknown; however, some possible interactive factors include: histamine release from mast cells and basophiles, uremic skin, cutaneous mast cells proliferation, adipose cells atrophy, electrolyte imbalance, and accumulation of bile acids. Since histamine is the main proposed mediator in pruritus, the goal of this study was to evaluate the role of antihistamines in controling of pruritus of patients with chronic renal failure. This study was done as a before - after study during one year period in dialysis department of Imam Khomeini hospital. Methods: Thirty patients complied with inclusion criteria were entered in the study. Treatment strategy was: 2 weeks treatment with hydroxyzine 25 mg TDS, followed by one week wash-out period, then 2 weeks ketotifen therapy 1mg BID and finally two weeks treatment with chlorpheniramine 4mg BD following one week washout period after ketotifen therapy. Pruritus severity before and after each treatment period was evaluated with Pruritus Severity Score (PSS chart. Results: The mean PSS reduction by hydroxyzine, ketotifen and chlorpheniramine, were 33%, 4.5% and 20%, respectively. Conclusion: PSS improvement with hydroxyzine and chlorpheniramine was statistically significant (p<0.001. However, ketotifen induced pruritus reduction was not considerably significant.

  11. Comparative in vitro toxicity of grape- and citrus-farm dusts.

    Science.gov (United States)

    Vallyathan, Val; Pack, Donna; Leonard, Steve; Lawson, Robert; Schenker, Marc; Castranova, Vince

    2007-01-15

    Agricultural workers are exposed to a variety of airborne dusts, including crystalline silica and other inorganic minerals. This study was designed to characterize the organic and inorganic components of agricultural dusts in California grape- and citrus-farm fields and to compare their cytotoxicity using in vitro toxicity bioassays as predictors of pathogenicity. Aerosolized dusts collected from farm fields were characterized by scanning-electron-microscopic energy-dispersive x-ray analysis, x-ray diffraction, trace metal analysis by plasma emission spectroscopy, and surface area measurements. As indicators of cytotoxicity, cell viability, release of alveolar enzymes activities (lactate dehydrogenase, N-acetyl glucosaminidase), production of reactive oxygen species (ROS), such as H2O2 and hydroxyl radical (OH), and lipid peroxidation were monitored after exposure of cells to grape- and citrus-farm dusts or inorganic components of these dusts. In addition, activation of nuclear factor kappa B and activator protein-1 were evaluated at the peak time for response of 36 h postexposure. All toxicity studies were done in comparison with crystalline silica of similar particle size and diameter using the same mass concentrations as farm dusts. The results showed that inorganic minerals in the aerosolized farm dust fractions were mostly composed of aluminum silicates, crystalline silica, and free iron. Crystalline silica used in these studies was more cytotoxic than grape- and citrus-farm dusts. However, in general, citrus farm dust exhibited the greatest ability to generate ROS and induce lipid peroxidation. These results support human epidemiologic studies, reporting an increased incidence of pulmonary fibrosis in farm workers, by documenting the potential of farm dusts to induce oxidative stress and initiate disease development.

  12. Comparative assessment of in vitro and in vivo toxicity of azinphos methyl and its commercial formulation.

    Science.gov (United States)

    Güngördü, Abbas; Uçkun, Miraç

    2015-09-01

    The toxic effects of Gusathion (GUS), which is a commercial organophosphate (OP) pesticide, and also its active ingredient, azinphos methyl (AzM), are evaluated comparatively with in vitro and in vivo studies. Initially, the 96-h LC50 values of AzM and GUS were estimated for two different life stages of Xenopus laevis, embryos, and tadpoles. The actual AzM concentrations in exposure media were monitored by high-performance liquid chromatography. Also, the sub-lethal effects of these compounds to tadpoles were determined 24 h later at exposure concentrations of 0.1 and 1 mg/L using selected biomarker enzymes such as acetylcholinesterase (AChE), carboxylesterase (CaE), glutathione S-transferase (GST), glutathione reductase, lactate dehydrogenase, and aspartate aminotrasferase. Differences in AChE inhibition capacities of AzM and GUS were evaluated under in vitro conditions between frogs and fish in the second part of this study. The AChE activities in a pure electrical eel AChE solution and in brain homogenates of adult Cyprinus carpio, Pelophylax ridibundus, and X. laevis were assayed after in vitro exposure to 0.05, 0.5, 5, and 50 mg/L concentrations of AzM and GUS. According to in vivo studies AChE, CaE and GST are important biomarkers of the effect of OP exposure while CaE may be more effective in short-term, low-concentration exposures. The results of in vitro studies showed that amphibian brain AChEs were relatively more resistant to OP exposure than fish AChEs. The resistance may be the cause of the lower toxicity/lethality of OP compounds to amphibians than to fish.

  13. Comparative acute toxicity of DDT metabolites among American and European species of planarians.

    Science.gov (United States)

    Bonner, J C; Wells, M R

    1987-01-01

    1. DDT metabolism in a North American species of planarian leads to the formation of metabolites more toxic than the parent compound. 2. The increased toxicity of DDT metabolites is similar to acute toxicity data reported previously in a European species. 3. It is suggested that planarians lack a direct mechanism for DDT detoxification, since two North American and one European species are known to metabolize DDT initially to DDE and DDD.

  14. How toxic is the depleted uranium to crayfish Procambarus clarkii compared with cadmium?

    Science.gov (United States)

    Al Kaddissi, Simone; Simon, Olivier; Elia, Antonia Concetta; Gonzalez, Patrice; Floriani, Magali; Cavalie, Isabelle; Camilleri, Virginie; Frelon, Sandrine; Legeay, Alexia

    2016-02-01

    Due to a lack of information on the assessment of uranium's (U) toxicity, our work aimed to compare the effects of U on the crayfish Procambarus clarkii with those of the well documented metal: cadmium (Cd). Accumulation and impacts at different levels of biological organization were assessed after acute (40 µM Cd or U; 4-10 days) and chronic (0.1 µM Cd or U; 30-60 days) exposures. The survival rates demonstrated the high tolerance of this species toward both metals and showed that Cd had a greater effect on the sustainability of crayfish. The concentration levels of Cd and U accumulated in gills and hepatopancreas were compared between both conditions. Distinctions in the adsorption capacities and the mobility of the contaminants were suspected. Differences in the detoxification mechanisms of both metals using transmission electron microscopy equiped with an energy dispersive X-ray were also pointed out. In contrast, comparison between the histological structures of contaminated hepatopancreas showed similar symptoms. Principal component analyses revealed different impacts of each metal on the oxidative balance and mitochondria using enzymatic activities and gene expression levels as endpoints. The observation that U seemed to generate more oxidative stress than Cd in our conditions of exposure is discussed.

  15. Rapid blood clearance and lack of long-term renal toxicity of {sup 177}Lu-DOTATATE enables shortening of renoprotective amino acid infusion

    Energy Technology Data Exchange (ETDEWEB)

    Kashyap, Raghava; Eu, Peter [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); Jackson, Price [Peter MacCallum Cancer Centre, Department of Physical Sciences, Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); The University of Melbourne, Departments of Medicine and Radiology, Melbourne (Australia); Beauregard, Jean-Mathieu [Universite Laval, Department of Radiology, Quebec City (Canada); Zannino, Diana [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne (Australia)

    2013-12-15

    The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. The whole-blood clearance of {sup 177}Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation. (orig.)

  16. Multicentre, parallel-group, comparative trial evaluating the efficacy and safety of sugammadex in patients with end-stage renal failure or normal renal function.

    NARCIS (Netherlands)

    Staals, L.M.; Snoeck, M.M.J.; Driessen, J.J.; Flockton, E.A.; Heeringa, M.; Hunter, J.M.

    2008-01-01

    BACKGROUND: Sugammadex, a modified gamma-cyclodextrin, is the first selective relaxant binding agent that specifically encapsulates the steroidal neuromuscular blocking agent, rocuronium. The action of rocuronium is prolonged in patients with renal failure. As sugammadex is primarily cleared

  17. Nicotine Exposure Augments Renal Toxicity of 5-aza-cytidine Through p66shc: Prevention by Resveratrol.

    Science.gov (United States)

    Arany, Istvan; Hall, Samuel; Faisal, Amir; Dixit, Mehul

    2017-08-01

    We have shown that either chronic nicotine (NIC) exposure or 5-aza-cytidine (AZA) augments oxidative stress-dependent injury through stimulating p66shc in renal cells. Hence, NIC could exacerbate adverse effects of AZA while antioxidants such as resveratrol (RES) could prevent it. Renal proximal tubule cells (NRK52E) were treated with 20 μM RES prior to 200 μM NIC plus 100 nM AZA and cell injury (LDH release) was determined. Reporter luciferase assays determined p66shc activation and RES-induced antioxidant responses. Genetic manipulations identified the mechanism of RES action. NIC exacerbated AZA-dependent injury via augmenting p66shc transcription. While RES suppressed NIC+AZA-mediated injury, -surprisingly-it further enhanced activity of the p66shc promoter. RES protected cells via the cytoplasmic p66shc/Nrf2/heme oxygenase-1 (HO-1) axis. RES can protect the kidney from adverse effects of NIC in patients undergoing anticancer therapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Comparative In vivo, Ex vivo, and In vitro Toxicity Studies of Engineered Nanomaterials

    Science.gov (United States)

    Efforts to reduce the number of animals in engineered nanomaterials (ENM) toxicity testing have resulted in the development of numerous alternative toxicity testing methods, but in vivo and in vitro results are still evolving and variable. This inconsistency could be due to the f...

  19. Development of Comparative Toxicity Potentials of TiO2 Nanoparticles for Use in Life Cycle Assessment

    DEFF Research Database (Denmark)

    Ettrup, Kim; Kounina, Anna; Hansen, Steffen Foss

    2017-01-01

    quantitatively addressed the toxic impacts caused by released nanoparticles, thus leading to potential biases in their conclusions. Here, we address this gap and aim to provide a framework for calculating characterization factors or comparative toxicity potentials (CTP) for nanoparticles and derive CTP values...... for freshwater ecotoxicity and human toxicity, both cancer effects and noncancer effects. Our results appeared plausible after benchmarking with CTPs for other nanoparticles and substances present in the USEtox database, while large differences were observed with CTP values for TiO2 nanoparticles published...... in earlier studies. Assumptions, which were performed in those previous studies because of lack of data and knowledge at the time they were made, primarily explain such discrepancies. For future assessment of potential toxic impacts of TiO2 nanoparticles in LCA studies, we therefore recommend the use of our...

  20. Lessons learned from the comparative study between renal mass biopsy and the analysis of the surgical specimen.

    Science.gov (United States)

    Domínguez-Esteban, M; Villacampa-Aubá, F; Garcia-Muñóz, H; Tejido Sánchez, A; Romero Otero, J; de la Rosa Kehrmann, F

    2014-12-01

    The role of renal mass (RM) biopsy is currently under discussion. As a result of the progressive increase in the incidental diagnosis of RMs (which have a higher percentage of benignity and well-differentiated cancers), new approaches have emerged such as observation, especially with elderly patients or those with significant comorbidity. RM biopsy (RMB) should provide sufficient information for making this decision, but so far this has not been the case. We examine our prospective series of in-bench RMBs after surgery and compare them with the anatomy of the removed specimen. We obtained (prospectively, in-bench and with a 16-gauge needle) 4 biopsies of RMs operated on in our department from October 2008 to December 2009. These RMs were analyzed by 2 uropathologists and compared with the results of the specimen. We analyzed 188 biopsies (47 RMs); 12.75% were "not valid". The ability of biopsy to diagnose malignancy or benignity was 100%, and the coincidence in the histological type was 95%. The success in determining the tumor grade was 100% when the cancer was low-grade and 62% when high-grade. None of the analyzed data (necrosis, size, etc.) influenced the results in a statistically significant manner. RMB with a 16-G needle enables the differentiation between malignancy and benignity in 100% of cases, with a very similar diagnostic accuracy in the tumor type. Tumor grade is still the pending issue with renal mass biopsy. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

  1. Comparative clinical evaluation of Boerhavia diffusa root extract with standard Enalapril treatment in Canine chronic renal failure

    Directory of Open Access Journals (Sweden)

    Nethaji Lokeswar Oburai

    2015-01-01

    Full Text Available Background: Complementing herbal drugs with conservative modern treatment could improve renal condition in canine chronic renal failure (CRF. Objective: In this study, clinical evaluation of Boerhavia diffusa root extract was carried out in CRF in dogs in comparison with standard enalapril. Materials and Methods: A total of 20 dogs of mixed breeds suffering from CRF from 1 to 2 months were divided into two groups (n = 10 and treated as follows: Group I - Enalapril at 0.5 mg/kg p.o. once daily for 90 days + amoxicillin and cloxacillin at 25 mg/kg i.m. once daily for 1-week; Group II - B. diffusa root extract at 500 mg p.o per dog daily for 90 days. Both groups were maintained on a supportive fluid therapy. The data were analyzed using paired t-test and one-way ANOVA followed by Dunnett's post-hoc test. Results: CRF caused a significant (P < 0.05 increase in systolic and diastolic blood pressure, serum creatinine, urea nitrogen, sodium, potassium, phosphorus, urinary protein, alkaline phosphatase (ALP, and glutamyl transferase (GGT. A significant (P < 0.05 decrease in hemoglobin and total erythrocyte count (TEC was also observed. Nephrosonography revealed indistinct corticomedullary junction, altered renal architecture, hyper-echoic cortex, medulla, and sunken kidneys. Both the treatments significantly (P < 0.05 reduced systolic and diastolic blood pressure by day 30. Serum Creatinine, urea nitrogen, phosphorus, urinary protein, ALP, and GGT showed significant (P < 0.05 reduction by day 60 in both the treatments. However, potassium levels were normalized only by B. diffusa root extract treatment by day 30. Both the treatments failed to show a significant improvement in nephrosonographic picture even after 90 days posttreatment. Conclusions: In conclusion, the efficacy of B. diffusa root extract was comparable to standard enalapril treatment of CRF in dogs.

  2. The toxicity of silver and silica nanoparticles in comparable human and mouse cell lines

    DEFF Research Database (Denmark)

    Foldbjerg, Rasmus; Beer, Christiane; Sutherland, Duncan S

    The toxicity of silica (SiO2) and PVP-coated silver (Ag) nanoparticles (NPs) was investigated in two pairs of human or mouse cell lines originating from lung epithelium (A549 and ASB-XIV) and macrophages (THP-1 and J744A.1). Both NPs were characterized in H2O and cell media and demonstrated...... the question whether increased ROS were caused by the NPs or as a consequence of cell death. Induction of ROS was also assessed by the comet assay and modifications of DNA. In both human and murine epithelial lung cells, the EC50 NP concentrations from the WST-8 assay correlated well with results from...... the annexin V/PI assay. Death at EC50 in the lung cells was equally due to apoptosis and necrosis after exposure to either NP. However, large discrepancies were found when comparing EC50 values from the WST-8 assay in macrophages to results from the Annexin V/PI assay. The WST-8 assay appeared to overestimate...

  3. Comparative toxic effects of formulated simazine on Vibrio fischeri and gilthead seabream (Sparus aurata L.) larvae.

    Science.gov (United States)

    Arufe, M I; Arellano, J; Moreno, M J; Sarasquete, C

    2004-12-01

    The use of Early Life Stage (ELS) tests is a useful tool in risk assessment. The purpose of this study was to compare the sensitivity of the seabream (Sparus aurata) larvae with the extensively used Microtox test on a commercial formulation containing simazine, an s-triazine herbicide. To this end, survival, growth and histopathological changes displayed by seabream yolk sac larvae exposed during 72 h post-hatching to nominal concentrations of the commercial preparation up to its saturating concentration in water, and bioluminescence of the marine bacteria Vibrio fischeri (Microtox) were studied. Survival of larvae after three days of exposure was significantly reduced in the highest (4.5 mg/l) concentration, but no effects on growth were found in any of the simazine treatments. The 72 h LC50 value for yolk sac larvae was estimated as 4.19 mg/l. Commercial grade simazine did not exert any significant toxicity to the marine bacterium V. fischeri at the concentrations tested.

  4. A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates.

    Directory of Open Access Journals (Sweden)

    Chen Chen

    Full Text Available BACKGROUND: Streptococcus suis serotype 2 (SS2 is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS, which was originally associated with Streptococcus pyogenes (GAS in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI. Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.

  5. Comparative Metagenomics of Toxic Freshwater Cyanobacteria Bloom Communities on Two Continents

    Energy Technology Data Exchange (ETDEWEB)

    Steffen, Morgan M [ORNL; Li, Zhou [ORNL; Effler, Chad [Department of Microbiology, University of Tennessee; Hauser, Loren John [ORNL; Boyer, Gergory [College of Environmental Science and Forestry, State University of New York, Syracuse; Wilhelm, Steven W [ORNL

    2012-01-01

    Toxic cyanobacterial blooms have persisted in freshwater systems around the world for centuries and appear to be globally increasing in frequency and severity. Toxins produced by bloom-associated cyanobacteria can have drastic impacts on the ecosystem and surrounding communities, and bloom biomass can disrupt aquatic food webs and act as a driver for hypoxia. Little is currently known regarding the genomic content of the Microcystis strains that form blooms or the companion heterotrophic community associated with bloom events. To address these issues, we examined the bloomassociated microbial communities in single samples from Lake Erie (North America), Lake Tai (Taihu, China), and Grand Lakes St. Marys (OH, USA) using comparative metagenomics. Together the Cyanobacteria and Proteobacteria comprised .90% of each bloom bacterial community sample, although the dominant phylum varied between systems. Relative to the existing Microcystis aeruginosa NIES 843 genome, sequences from Lake Erie and Taihu revealed a number of metagenomic islands that were absent in the environmental samples. Moreover, despite variation in the phylogenetic assignments of bloomassociated organisms, the functional potential of bloom members remained relatively constant between systems. This pattern was particularly noticeable in the genomic contribution of nitrogen assimilation genes. In Taihu, the genetic elements associated with the assimilation and metabolism of nitrogen were predominantly associated with Proteobacteria, while these functions in the North American lakes were primarily contributed to by the Cyanobacteria. Our observations build on an emerging body of metagenomic surveys describing the functional potential of microbial communities as more highly conserved than that of their phylogenetic makeup within natural systems.

  6. Clinical evaluation of renal functional dynamic study with [sup 99m]Tc-MAG3; Comparative study with [sup 123]I-OIH using deconvolution analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Shigeki; Kawaguchi, Tatsuya; Takano, Katsuhiro; Tanaka, Naoshi; Nishide, Yoshiya; Takeda, Kan; Hioki, Takuichi; Kawamura, Hisaichi; Nakagawa, Tsuyoshi (Mie Univ., Tsu (Japan). School of Medicine)

    1994-02-01

    A Phase III clinical study compared Tc-99m mercaptoacetylglycylglycylglycine (Tc-99m MAG3) with I-123 orthoiodohippurate (I-123 OIH) in functional radionuclide renal study using deconvolution analysis. The subjects were six patients with diabetic nephropathy, four with renal transplants and seven healthy volunteers. Tc-99m MAG3 tended to give a prolonger transit time than I-123 OIH, although there was no significant correlation between the two radiopharmaceuticals. The shape of the transfer function showed the same distribution pattern of the transit time in Tc-99m MAG3 and I-123 OIH, revealing that both radiopharmaceuticals had the analogous renal dynamics. Regarding effective renal plasma flow, there was a good correlation between the two drug, especially for those with renal transplants. In all patients with renal transplants, defects were seen on functional images when using I-123 OIH, but not seen when using Tc-99m MAG3. This may be attributable to artifacts caused by insufficient dosage of I-123 OIH. Thus Tc-99m MAG3 is considered more useful for evaluating renal function in functional radionuclide imaging because its dosage can be adjusted voluntarily. (N.K.).

  7. Comparative Study between Slow Shock Wave Lithotripsy and Fast Shock Wave Lithotripsy in the Management of Renal Stone

    Directory of Open Access Journals (Sweden)

    AKM Zamanul Islam Bhuiyan

    2013-01-01

    Full Text Available Background: Renal calculi are frequent causes of ureteric colic. Extracorporeal shock wave lithotripsy is the most common treatment of these stones. It uses focused sound waves to break up stones externally. Objective: To compare the efficiency of slow and fast delivery rate of shock waves on stone fragmentation and treatment outcome in patients with renal calculi. Materials and Methods: This prospective study was done in the department of Urology, National Institute of Kidney diseases and Urology, Sher-e-Bangla Nagar, Dhaka from July 2006 to June 2007. Total 90 patients were treated using the Storz Medical Modulith ® SLX lithotripter. Patients were divided into Group A, Group B and Group C – each group having 30 subjects. Group A was selected for extracorporeal shockwave lithotripsy (ESWL by 60 shock waves per minute, Group B by 90 shock waves per minute and Group C by 120 shock waves per minute. Results: Complete clearance of stone was observed in 24 patients in Group A and 13 patients in both Group B and Group C in first session. In Group A only 3 patients needed second session but in Group B and Group C, 12 and 8 patients needed second session. In Group A only one patient needed third session but third session was required for 3 patients in Group B and 5 patients in Group C for complete clearance of stone. In Group A, subsequent sessions were performed under spinal anesthesia and in Group B under sedation and analgesia (p>0.001. Mean number of sessions for full clearance of stones in group A was 1.37 ± 0.85, in Group B was 1.8 ± 0.887 and in Group C was 2.0 ± 1.083. Significant difference was observed in term of sessions among groups (p>0.05. In first follow-up, complete clearance of stones was seen in 24 patients in Group A and 13 in both Group B and Group C. In second follow-up, 3 patients in Group A, 12 in Group B and 8 in Group C showed complete clearance of stones. It was observed that rate of stone clearance was higher in Group A

  8. Comparative toxicity of nonylphenol, nonylphenol-4-ethoxylate and nonylphenol-10-ethoxylate to wheat seedlings (Triticum aestivum L.).

    Science.gov (United States)

    Zhang, Qingming; Wang, Feifei; Xue, Changhui; Wang, Caixia; Chi, Shengqi; Zhang, Jianfeng

    2016-09-01

    Nonylphenol polyethoxylates (NPEOs) are a group of surfactants that are widely used in industrial and household products and often detected in the environment. The metabolite of NPEOs, named nonylphenol (NP), has proven to be an endocrine disruptor, and its environmental behavior and eco-toxicity have been widely investigated in previous studies. However, to the best of our knowledge, insight into the toxicity differences of NP and NPEOs on important crops remains limited. Therefore, this study investigated the comparative toxicity of NP, nonylphenol-4-ethoxylate (NP4EO), and nonylphenol-10-ethoxylate (NP10EO) on wheat seedlings using hydroponic experiments. The results indicated that NP is most toxic to wheat followed by NP4EO, and NP10EO is the least toxic to wheat. The adverse effects of NP on wheat were observed for all the tested parameters including germination, shoot length, root length, chlorophyll, lipid peroxidation, and enzymatic activities. To gain insight into the molecular response, we analyzed the transcript abundance of SOD-Cu/Zn and CAT with NP, NP4EO, and NP10EO exposure using quantitative real-time PCR. The data revealed that both genes exhibited up- or down-regulated expression patterns that were consistent with the activities of the two enzymes. This result further conformed that NP is most toxic to wheat plants.

  9. Comparative toxicity of methanol and N,N-dimethylformamide to freshwater fish and invertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Poirier, S.H.; Knuth, M.L.; Anderson-Buchou, C.D.; Brooke, L.T.; Lima, A.R.; Shubat, P.J.

    1986-10-01

    The organic solvents methanol and N,N-dimethylformamide (DMF) are used widely as industrial solvents. Although some toxicity data appear in the literature for methanol and DMF, there have been few studies which have been flow-through tests for a standard 48- or 96-h exposure period with measured toxicant concentrations. In this study, 96-h flow-through acute toxicity tests with methanol and DMF were conducted with three species of freshwater fish - rainbow trout (Salmo gairdneri), bluegill (Lepomis macrochirus) and fathead minnow (Pimephales promelas). Static acute toxicity tests (48 h) were conducted with DMF and two species of freshwater invertebrates - a midge (Paratanytarsus parthenogeneticus) and a daphnid (Daphnia magna). Median lethal (LC50) and median effect (EC50) concentrations for 96-h exposures were determined for fish and 48-h EC50's were determined for invertebrates.

  10. COMPARING THE RECOMMENDED DIETARY ALLOWANCE TO TOXICITY VALUES FOR ZN, SE, MN, AND MB

    Science.gov (United States)

    Certain essential nutrients can be toxic when ingested at dosages higher than the daily nutritional requirement. Research data for the essential trace elements, zinc, selenium, manganese and molybdenum have been reviewed by various government agencies for both their nutritional n...

  11. COMPARING THE RECOMMENDED DIETARY ALLOWANCE TO TOXICITY VALUES FOR ZN, SE, MN, AND MB

    Science.gov (United States)

    Certain essential nutrients can be toxic when ingested at dosages higher than the daily nutritional requirement. Research data for the essential trace elements, zinc, selenium, manganese and molybdenum have been reviewed by various government agencies for both their nutritional n...

  12. Comparative toxicity of carbaryl, carbofuran, cypermethrin and fenvalerate in Metaphire posthuma and Eisenia fetida -a possible mechanism.

    Science.gov (United States)

    Saxena, P N; Gupta, S K; Murthy, R C

    2014-02-01

    To establish the use of Metaphire posthuma as a sensitive test model for ecotoxicological studies, acute toxicity testing of carbaryl, carbofuran, cypermethrin and fenvalerate on Eisenia fetida and Metaphire posthuma were carried out. Two different types of bioassays, contact filter paper toxicity and soil toxicity bioassays were used to determine LC50 values for these insecticides. Among the tested chemicals, carbofuran was the most toxic to both the earthworm species. In paper contact method, 72 h-LC50 values of carbofuran in M. posthuma and E. fetida were found to be 0.08 μg/cm(2) and 1.55 μg/cm(2) respectively while in soil test, 14-d LC50 values were 0.49 mg/kg and 21.15 mg/kg respectively. On comparing the toxicity data of these chemicals for both the earthworm species, M. posthuma was found to be more sensitive than E. fetida. Based on the acute toxicity data, the order of toxicity of insecticides in both the test procedures was carbofuran>cypermethrin>carbaryl>fenvalerate for M. posthuma whereas for E. fetida it was carbofuran>carbaryl>fenvalerate>cypermethrin. Morphological changes also appeared in the organisms exposed to these chemicals which were more pronounced in M. posthuma at lower concentrations than E. fetida in both the test procedures. The results of the present study advocates the use of M. posthuma for ecotoxicity studies, being a more sensitive and reliable model than E. fetida. Based on the data on partial atomic charges, structural features and spectroscopic studies on carbaryl and carbofuran, a possible mechanism of toxicity of carbamate insecticides in earthworm was proposed.

  13. Lansoprazole Exacerbates Pemetrexed-Mediated Hematologic Toxicity by Competitive Inhibition of Renal Basolateral Human Organic Anion Transporter 3.

    Science.gov (United States)

    Ikemura, Kenji; Hamada, Yugo; Kaya, Chinatsu; Enokiya, Tomoyuki; Muraki, Yuichi; Nakahara, Hiroki; Fujimoto, Hajime; Kobayashi, Tetsu; Iwamoto, Takuya; Okuda, Masahiro

    2016-10-01

    Pemetrexed, a multitargeted antifolate, is eliminated by tubular secretion via human organic anion transporter 3 (hOAT3). Although proton pump inhibitors (PPIs) are frequently used in cancer patients, the drug interaction between PPIs and pemetrexed remains to be clarified. In this study, we examined the drug interaction between pemetrexed and PPIs in hOAT3-expressing cultured cells, and retrospectively analyzed the impact of PPIs on the development of hematologic toxicity in 108 patients who received pemetrexed and carboplatin treatment of nonsquamous non-small cell lung cancer for the first time between January 2011 and June 2015. We established that pemetrexed was transported via hOAT3 (Km = 68.3 ± 11.1 µM). Lansoprazole, rabeprazole, pantoprazole, esomeprazole, omeprazole, and vonoprazan inhibited hOAT3-mediated uptake of pemetrexed in a concentration-dependent manner. The inhibitory effect of lansoprazole was much greater than those of other PPIs and the apparent IC50 value of lansoprazole against pemetrexed transport via hOAT3 was 0.57 ± 0.17 µM. The inhibitory type of lansoprazole was competitive. In a retrospective study, multivariate analysis revealed that coadministration of lansoprazole, but not other PPIs, with pemetrexed and carboplatin was an independent risk factor significantly contributing to the development of hematologic toxicity (odds ratio: 10.004, P = 0.005). These findings demonstrated that coadministration of lansoprazole could exacerbate the hematologic toxicity associated with pemetrexed, at least in part, by competitive inhibition of hOAT3. Our results would aid clinicians to make decisions of coadministration drugs to avoid drug interaction-induced side effects for achievement of safe and appropriate chemotherapy with pemetrexed.

  14. Comparative assessment of essential and toxic metals in the blood of rheumatoid arthritis patients and healthy subjects.

    Science.gov (United States)

    Hashmi, G M Mujtba; Shah, Munir H

    2012-04-01

    The present study deals with the comparative evaluation of essential and toxic metals in rheumatoid arthritis and healthy donors. Blood samples collected from rheumatoid arthritis patients and healthy subjects were analysed for selected essential and toxic metals (Ca, Mg, Fe, Zn, Cu, Co, Mn, Cr, Cd and Pb). The samples were digested in nitric acid and perchloric acid mixture, followed by quantification of the metals using atomic absorption spectrometry. Mean levels of Ca, Mg, Fe and Zn were significantly higher in the blood of healthy donors; however, elevated levels of Cd, Co, Cr, Cu and Pb were observed in blood of the patients. The correlation coefficients among the selected metals in the blood of arthritis patients were significantly different compared with the healthy counterparts. Multivariate cluster analysis revealed mutual apportionment of the essential and toxic metals in blood of the patients, whereas, in controls, the essential and toxic metals revealed diverse apportionment. Variations in the metal levels with gender, residence and smoking habits were also evaluated in both donor groups. Relative distribution, correlation and apportionment of the essential and toxic metals in the blood of the patients were significantly different than of controls.

  15. Progress in treatment and study of renal toxicity by mercury poisoning%汞的肾毒性及治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    陈子安; 聂志勇; 李万华; 胡鹏遥; 隋昕; 邱泽武; 王永安

    2016-01-01

    Mercury is one of the common heavy-metal toxins,which can cause damage throughout the body in a variety of ways. Cases of renal toxicity of mercury poisoning are increasing clinically. However,little is known about nephrotoxicity mechanisms,and treatment remains unsatisfactory. The mechanism of mercury toxic nephropathy is reviewed in this paper,including the direct toxic effect on the kidney,the injury to the biomembrane system,generation of Hg-metallothionein,imbalance of intra⁃cellular calciumion,oxidative damage,induced apoptosis,and immune injury. Besides,the mechanism and limitation of common therapies,potential developments of the field are discussed. This review will facilitate further investigations therapies about both the mechanism and treatment of mercury toxic nephropathy.%汞是常见的重金属毒物,多种原因导致的急慢性汞中毒可对人体多个脏器产生严重损害。临床上因汞中毒导致的肾病逐年增多,其损伤机制尚不明确,治疗手段有限。本文就汞的肾毒性作用机制研究进展进行综述,包括汞对肾的直接毒性作用,生物膜系统受损,汞-金属硫蛋白复合物形成,胞内Ca2+平衡失调,氧化损伤,诱导细胞凋亡,免疫性损伤等。归纳总结了临床上常见治疗方法的机理及局限,并对几种当前研究的热点问题和发展方向进行了介绍,在此基础之上探究汞对肾造成损害的疾病模型,旨在为临床上慢性汞中毒导致的肾病的治疗方法提供相关支持。

  16. Comparative metagenomics of toxic freshwater cyanobacteria bloom communities on two continents.

    Science.gov (United States)

    Steffen, Morgan M; Li, Zhou; Effler, T Chad; Hauser, Loren J; Boyer, Gregory L; Wilhelm, Steven W

    2012-01-01

    Toxic cyanobacterial blooms have persisted in freshwater systems around the world for centuries and appear to be globally increasing in frequency and severity. Toxins produced by bloom-associated cyanobacteria can have drastic impacts on the ecosystem and surrounding communities, and bloom biomass can disrupt aquatic food webs and act as a driver for hypoxia. Little is currently known regarding the genomic content of the Microcystis strains that form blooms or the companion heterotrophic community associated with bloom events. To address these issues, we examined the bloom-associated microbial communities in single samples from Lake Erie (North America), Lake Tai (Taihu, China), and Grand Lakes St. Marys (OH, USA) using comparative metagenomics. Together the Cyanobacteria and Proteobacteria comprised >90% of each bloom bacterial community sample, although the dominant phylum varied between systems. Relative to the existing Microcystis aeruginosa NIES 843 genome, sequences from Lake Erie and Taihu revealed a number of metagenomic islands that were absent in the environmental samples. Moreover, despite variation in the phylogenetic assignments of bloom-associated organisms, the functional potential of bloom members remained relatively constant between systems. This pattern was particularly noticeable in the genomic contribution of nitrogen assimilation genes. In Taihu, the genetic elements associated with the assimilation and metabolism of nitrogen were predominantly associated with Proteobacteria, while these functions in the North American lakes were primarily contributed to by the Cyanobacteria. Our observations build on an emerging body of metagenomic surveys describing the functional potential of microbial communities as more highly conserved than that of their phylogenetic makeup within natural systems.

  17. Comparative metagenomics of toxic freshwater cyanobacteria bloom communities on two continents.

    Directory of Open Access Journals (Sweden)

    Morgan M Steffen

    Full Text Available Toxic cyanobacterial blooms have persisted in freshwater systems around the world for centuries and appear to be globally increasing in frequency and severity. Toxins produced by bloom-associated cyanobacteria can have drastic impacts on the ecosystem and surrounding communities, and bloom biomass can disrupt aquatic food webs and act as a driver for hypoxia. Little is currently known regarding the genomic content of the Microcystis strains that form blooms or the companion heterotrophic community associated with bloom events. To address these issues, we examined the bloom-associated microbial communities in single samples from Lake Erie (North America, Lake Tai (Taihu, China, and Grand Lakes St. Marys (OH, USA using comparative metagenomics. Together the Cyanobacteria and Proteobacteria comprised >90% of each bloom bacterial community sample, although the dominant phylum varied between systems. Relative to the existing Microcystis aeruginosa NIES 843 genome, sequences from Lake Erie and Taihu revealed a number of metagenomic islands that were absent in the environmental samples. Moreover, despite variation in the phylogenetic assignments of bloom-associated organisms, the functional potential of bloom members remained relatively constant between systems. This pattern was particularly noticeable in the genomic contribution of nitrogen assimilation genes. In Taihu, the genetic elements associated with the assimilation and metabolism of nitrogen were predominantly associated with Proteobacteria, while these functions in the North American lakes were primarily contributed to by the Cyanobacteria. Our observations build on an emerging body of metagenomic surveys describing the functional potential of microbial communities as more highly conserved than that of their phylogenetic makeup within natural systems.

  18. Composition and comparative toxicity of particulate matter emitted from a diesel and biodiesel fuelled CRDI engine

    Science.gov (United States)

    Gangwar, Jitendra N.; Gupta, Tarun; Agarwal, Avinash K.

    2012-01-01

    There is a global concern about adverse health effects of particulate matter (PM) originating from diesel engine exhaust. In the current study, parametric investigations were carried out using a CRDI (Common Rail Direct Injection) diesel engine operated at different loads at two different engine speeds (1800 and 2400 rpm), employing diesel and 20% biodiesel blends (B20) produced from Karanja oil. A partial flow dilution tunnel was employed to collect and measure the mass of the primary particulates from diesel and biodiesel blend collected on a 47 mm quartz substrate. The collected PM (particulate matter) was subjected to chemical analyses in order to assess the amount of Benzene Soluble Organic Fraction (BSOF) and trace metals using Inductively Coupled Plasma-Optical Emission Spectrometer (ICP-OES). For both diesel and biodiesel, BSOF results showed decreasing levels with increasing engine load. B20 showed higher BSOF as compared to those measured with diesel. The concentration of different trace metals analyzed also showed decreasing trends with increasing engine loads. In addition, real-time measurements for Organic Carbon (OC), Elemental Carbon (EC) and total particle-bound Polycyclic Aromatic Hydrocarbons (PAHs) were carried out on the primary engine exhaust coming out of the partial flow dilution tunnel. Analysis of OC/EC data suggested that the ratio of OC to EC decreases with corresponding increase in engine load for both fuels. A peak in PAH concentration was observed at 60% engine load at 1800 rpm and 20% engine load at 2400 rpm engine speeds almost identical for both kinds of fuels. Comparison of chemical components of PM emitted from this CRDI engine provides new insight in terms of PM toxicity for B20 vis-a-vis diesel.

  19. Renal cysteine conjugate C-S lyase mediated toxicity of halogenated alkenes in primary cultures of human and rat proximal tubular cells.

    Science.gov (United States)

    McGoldrick, Trevor A; Lock, Edward A; Rodilla, Vicente; Hawksworth, Gabrielle M

    2003-07-01

    Proximal tubular cells from human (HPT) and rat (RPT) kidneys were isolated, grown to confluence and incubated with S-(1,2-dichlorovinyl)- l-cysteine (DCVC), S-(1,2,2-trichlorovinyl)- l-cysteine (TCVC), S-(1,1,2,2-tetrafluoroethyl)- l-cysteine (TFEC) and S-(2-chloro-1,1-difluorethyl)- l-cysteine (CDFEC), the cysteine conjugates of nephrotoxicants. The cultures were exposed to the conjugates for 12, 24 and 48 h and the toxicity determined using the MTT assay. All four conjugates caused dose-dependent toxicity to RPT cells over the range 50-1,000 microM, the order of toxicity being DCVC>TCVC>TFEC=CDFEC. The inclusion of aminooxyacetic acid (AOAA; 250 microM), an inhibitor of pyridoxal phosphate-dependent enzymes such as C-S lyase, afforded protection, indicating that C-S lyase has a role in the bioactivation of these conjugates. In HPT cultures only DCVC caused significant time- and dose-dependent toxicity. Exposure to DCVC (500 microM) for 48 h decreased cell viability to 7% of control cell values, whereas co-incubation of DCVC (500 microM) with AOAA (250 microM) resulted in cell viability of 71%. Human cultures were also exposed to S-(1,2-dichlorovinyl)-glutathione (DCVG). DCVG was toxic to HPT cells, but the onset of toxicity was delayed compared with the corresponding cysteine conjugate. AOAA afforded almost complete protection from DCVG toxicity. Acivicin (250 microM), an inhibitor of gamma-glutamyl transferase (gamma-GT), partially protected against DCVG (500 microM)-induced toxicity at 48 h (5% viability and 53% viability in the absence and presence of acivicin, respectively). These results suggest that DCVG requires processing by gamma-GT prior to bioactivation by C-S lyase in HPT cells. The activity of C-S lyase, using TFEC as a substrate, and glutamine transaminase K (GTK) was measured in rat and human cells with time in culture. C-S lyase activity in RPT and HPT cells decreased to approximately 30% of fresh cell values by the time the cells reached

  20. Silencing megalin and cubilin genes inhibits myeloma light chain endocytosis and ameliorates toxicity in human renal proximal tubule epithelial cells.

    Science.gov (United States)

    Li, Min; Balamuthusamy, Saravanan; Simon, Eric E; Batuman, Vecihi

    2008-07-01

    Using target-specific short interfering (si) RNAs, we silenced the tandem endocytic receptors megalin and cubilin genes in cultured human renal proximal tubule epithelial cells. Transfection by siRNA resulted in up to 90% suppression of both megalin and cubilin protein and mRNA expression. In HK-2 cells exposed to kappa-light chain for up to 24 h, light chain endocytosis was reduced in either megalin- or cubilin-silenced cells markedly but incompletely. Simultaneous silencing of both the cubilin and megalin genes, however, resulted in near-complete inhibition of light chain endocytosis, as determined by measuring kappa-light chain protein concentration in cell cytoplasm and by flow cytometry using FITC-labeled kappa-light chain. In these cells, light chain-induced cytokine responses (interleukin-6 and monocyte chemoattractant protein-1) and epithelial-to-mesenchymal transition as well as the associated cellular and morphological alterations were also markedly suppressed. The results demonstrate that light chain endocytosis is predominantly mediated by the megalin-cubilin tandem endocytic receptor and identify endocytosis as a key step in light chain cytotoxicity. Blocking light chain endocytosis prevents its nephrotoxic effects on human kidney proximal tubule cells.

  1. Comparative effect of olmesartan and candesartan on lipid metabolism and renal function in patients with hypertension: a retrospective observational study

    Science.gov (United States)

    2011-01-01

    Background Angiotensin II receptor blockers (ARBs), including olmesartan and candesartan, are widely used antihypertensive agents. Many clinical studies have demonstrated that ARBs have organ-protecting effects, e.g., cardioprotection, vasculoprotection and renoprotection. However, the effect of prolonged olmesartan monotherapy on lipid metabolism in patients with hypertension is less well studied. We performed a retrospective observational study to compare the effects of olmesartan with those of candesartan, focusing on lipid metabolism and renal function. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and Feb 28, 2011, to identify cohorts of new olmesartan users (n = 168) and candesartan users (n = 266). We used propensity-score weighting to adjust for differences in all covariates (age, sex, comorbid diseases, previous drugs) between olmesartan and candesartan users, and compared serum chemical data including serum triglyceride (TG), LDL-cholesterol (LDL-C), total cholesterol (TC), potassium, creatinine and urea nitrogen. The mean exposure of olmesartan and candesartan users was 126.1 and 122.8 days, respectively. Results After adjustment, there were no statistically significant differences in all covariates between olmesartan and candesartan users. The mean age was 60.7 and 61.0 years, and 33.4% and 33.7% of olmesartan and candesartan users were women, respectively. There were no statistically significant differences in mean values for all laboratory tests between baseline and during the exposure period in both olmesartan and candesartan users. In olmesartan users, the reduction of serum TG level was significant in comparison with that in candesartan users. Other parameters of lipid profile and renal function showed no statistically significant difference in the change from baseline to during the exposure period between olmesartan and candesartan users. Conclusions In this study, we

  2. Comparative effect of olmesartan and candesartan on lipid metabolism and renal function in patients with hypertension: a retrospective observational study

    Directory of Open Access Journals (Sweden)

    Nakayama Tomohiro

    2011-08-01

    Full Text Available Abstract Background Angiotensin II receptor blockers (ARBs, including olmesartan and candesartan, are widely used antihypertensive agents. Many clinical studies have demonstrated that ARBs have organ-protecting effects, e.g., cardioprotection, vasculoprotection and renoprotection. However, the effect of prolonged olmesartan monotherapy on lipid metabolism in patients with hypertension is less well studied. We performed a retrospective observational study to compare the effects of olmesartan with those of candesartan, focusing on lipid metabolism and renal function. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and Feb 28, 2011, to identify cohorts of new olmesartan users (n = 168 and candesartan users (n = 266. We used propensity-score weighting to adjust for differences in all covariates (age, sex, comorbid diseases, previous drugs between olmesartan and candesartan users, and compared serum chemical data including serum triglyceride (TG, LDL-cholesterol (LDL-C, total cholesterol (TC, potassium, creatinine and urea nitrogen. The mean exposure of olmesartan and candesartan users was 126.1 and 122.8 days, respectively. Results After adjustment, there were no statistically significant differences in all covariates between olmesartan and candesartan users. The mean age was 60.7 and 61.0 years, and 33.4% and 33.7% of olmesartan and candesartan users were women, respectively. There were no statistically significant differences in mean values for all laboratory tests between baseline and during the exposure period in both olmesartan and candesartan users. In olmesartan users, the reduction of serum TG level was significant in comparison with that in candesartan users. Other parameters of lipid profile and renal function showed no statistically significant difference in the change from baseline to during the exposure period between olmesartan and candesartan users. Conclusions

  3. Skin Cancer Risk in Hematopoietic Stem-Cell Transplant Recipients Compared With Background Population and Renal Transplant Recipients

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Gniadecki, Robert; Hædersdal, Merete

    2016-01-01

    IMPORTANCE: While a high risk of nonmelanoma skin cancer is well recognized in solid-organ transplant recipients, the risk of skin cancer in hematopoietic stem-cell transplant (HSCT) recipients has not been extensively studied. OBJECTIVE: To determine the risk of cutaneous cancer in HSCT recipients...... and compare it with the risk in renal transplant recipients (RTRs) and individuals who have not received any transplant. DESIGN, SETTING, AND PARTICIPANTS: A nationwide population-based cohort study from the Danish National Hospital Register including 3302 patients who underwent HSCT (1007 allogeneic, 2295...... cancer between transplant recipients and background population, we used a stratified proportional hazard regression model for hazard ratio (HR) estimations. By use of the cumulative incidence, we estimated 5- and 10-year risks of skin cancers. All RTR and HSCT recipients were treated and followed up...

  4. Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii

    Science.gov (United States)

    Sparling, D.W.; Fellers, G.

    2007-01-01

    Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24 h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations. ?? 2006 Elsevier Ltd. All rights reserved.

  5. Comparative toxicity of diphacinone to northern bobwhite (Colinus virginianus) and American kestrels (Falco sparverius)

    Science.gov (United States)

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Johnston, John J.

    2010-01-01

    The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be about 20 times greater to American kestrels (LD50=97 mg/kg) than to northern bobwhite (LD50=2,014 mg/kg). Several precise and sensitive clotting assays (prothrombin time, Russell's Viper venom time, thrombin clotting time) were adapted for use in these species, and this combination of assays is recommended to detect effects of diphacinone and other rodenticides on coagulation. Oral administration of diphacinone over a range of doses (sublethal to the extrapolated LD15) prolonged prothrombin time and Russell's Viper venom time within 24 to 48 hrs post-exposure. Prolongation of in vitro clotting time reflects impaired coagulation complex activity and was detected before or at the onset of overt signs of toxicity and lethality. These data will assist in the development of a pharmacodynamic model to assess and predict rodenticide toxicity to non-target avian species.

  6. Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii.

    Science.gov (United States)

    Sparling, D W; Fellers, G

    2007-06-01

    Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations.

  7. USEtox fate and ecotoxicity factors for comparative assessment of toxic emissions in Life Cycle Analysis

    DEFF Research Database (Denmark)

    Andrew D, Henderson; Hauschild, Michael Zwicky; Van de Meent, Dik;

    2011-01-01

    The USEtox model was developed in a scientific consensus process involving comparison of and harmonization between existing environmental multimedia fate models. For freshwater ecosystem toxicity, it covers the entire impact pathway, i.e., transforming a chemical emission into potential impacts......, the effect factor, which is obtained from laboratory measurements of substance toxicity to different phyla, strongly controls freshwater ecotoxicity, with a range of up to 10 orders of magnitude. Chemical-specific differences in multimedia transfer influence the CF for freshwater emissions by less than two...

  8. Addressing Geographic Variability in the Comparative Toxicity Potential of Copper and Nickel in Soils

    DEFF Research Database (Denmark)

    Owsianiak, Mikolaj; Rosenbaum, Ralph K.; Huijbregts, Mark A. J.;

    2013-01-01

    in the soil was introduced into the definition of CTP. Geographic differences in fate, accessibility, bioavailability, and terrestrial toxicity were assessed by combining the USEtox characterization model, empirical regression models, and terrestrial biotic ligand models. The median CTPs for Cu and Ni with 95...... the fate and bioavailability of Cu in soils. In contrast, the geographic variability of 3 orders of magnitude in the CTP of Ni can mainly be explained by differences in pore water concentration of magnesium (Mg2+). Mg2+ competes with Ni2+ for binding to biotic ligands, influencing the toxicity. Our...

  9. Relationship between the development of hepato-renal toxicity and cadmium accumulation in rats given minimum to large amounts of cadmium chloride in the long-term: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Mitsumori, K.; Shibutani, M.; Onodera, H. [Division of Pathology, National Institute of Health Sciences, Tokyo (Japan); Sato, S. [Ina Research Inc., Ina-shi, Nagano-ken (Japan); Nakagawa, J. [Division of Water Research, Tokyo Metropolitan Research Laboratory of Public Health (Japan); Hayashi, Y. [Department of Pharmaceutical Sciences, Kitasato University, Tokyo (Japan); Ando, M. [Division of Environmental Health Chemistry, National Institute of Health Sciences, Tokyo (Japan)

    1998-09-01

    We wished to clarify the relationship between the sensitivity to induce hepato-renal toxicity and the level of cadmium (Cd) in the organs of rats exposed to minimum to large amounts of cadmium chloride (CdCl{sub 2}). For this purpose, groups of female Sprague-Dawley (SD) rats, each consisting of 24 animals, were fed diet containing CdCl{sub 2} at concentrations of 0, 8, 40, 200, and 600 ppm for 2, 4, and 8 months from 5 weeks of age. All surviving rats given 600 ppm Cd were killed at 4 months because of deterioration of their general condition. Animals of this group showed anemia and decreased hematopoiesis in the bone marrow, in addition to reduction of cancellous bone in their femurs. Hepatotoxicity was observed after 2 months in the groups treated with {>=}200 ppm. By 4 months, the rats in the 600 ppm group had developed periportal liver cell necrosis. Renal toxicity characterized by degeneration of proximal tubular epithelia was apparent in the groups treated with {>=}200 ppm from 2 months, becoming more prominent in the high-dose rats at 4 months. Hepatic accumulation of Cd increased linearly with the duration of treatment. In contrast, the concentration of Cd in the renal cortex of rats treated with 600 ppm reached a plateau level of {proportional_to}250 {mu}g/g within the first 2 months. The renal concentration of Cd in the 200 ppm group when renal toxic lesions were first detected at 2 months ranged from 104 to 244 {mu}g/g. No renal lesions were observed in the 40 ppm group after 8 months, despite the presence of 91-183 {mu}g/g of Cd in the kidneys. The results thus suggest that renal toxicity would not be induced by treatment with minimum amounts of CdCl{sub 2} for periods longer than 8 months, although accumulation of Cd might gradually progress. A further 2-year feeding study of CdCl{sub 2} and Cd-polluted rice is now in progress. (orig.) (orig.) With 6 figs., 3 tabs., 20 refs.

  10. Antioxidant Pre-Treatment Reduces the Toxic Effects of Oxalate on Renal Epithelial Cells in a Cell Culture Model of Urolithiasis

    Directory of Open Access Journals (Sweden)

    Tomislav Kizivat

    2017-01-01

    Full Text Available Urolithiasis is characterized by the formation and retention of solid crystals within the urinary tract. Kidney stones are mostly composed of calcium oxalate, which predominantly generates free radicals that are toxic to renal tubular cells. The aim of the study is to explore possible effects of antioxidant pre-treatment on inhibition of oxidative stress. Three cell lines were used as in vitro model of urolithiasis: MDCK I, MDCK II and LLC-PK1. Oxidative stress was induced by exposure of cells to sodium oxalate in concentration of 8 mM. In order to prevent oxidative stress, cells were pre-treated with three different concentrations of l-arginine and vitamin E. Oxidative stress was evaluated by determining the expression of superoxide dismutase (SOD, osteopontin (OPN, and by the concentration of glutathione (GSH. In all three cell lines, pre-treatment of antioxidants increased cell survival. Positive correlation of SOD and OPN expression as well as GSH concentration was observed in all groups of cells. Our results indicate that an antioxidant pre-treatment with l-arginine and vitamin E is able to hamper oxalate-induced oxidative stress in kidney epithelial cells and as such could play a role in prevention of urolithiasis.

  11. [A comparative in vitro study of cell toxicity of clinically used antiseptics].

    Science.gov (United States)

    Hirsch, T; Jacobsen, F; Rittig, A; Goertz, O; Niederbichler, A; Steinau, H U; Seipp, H M; Steinstraesser, L

    2009-12-01

    Local skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells. Three antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA. Lavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (pOctenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept. This study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.

  12. Comparative analysis of acute toxic poisoning in 2003 and 2011: analysis of 3 academic hospitals.

    Science.gov (United States)

    Jang, Hak-Soo; Kim, Jung-Youn; Choi, Sung-Hyuk; Yoon, Young-Hoon; Moon, Sung-Woo; Hong, Yun-Sik; Lee, Sung-Woo

    2013-10-01

    Social factors may affect the available sources of toxic substances and causes of poisoning; and these factors may change over time. Additionally, understanding the characteristics of patients with acute toxic poisoning is important for treating such patients. Therefore, this study investigated the characteristics of patients with toxic poisoning. Patients visiting one of 3 hospitals in 2003 and 2011 were included in this study. Data on all patients who were admitted to the emergency departments with acute toxic poisoning were retrospectively obtained from medical records. Total 939 patients were analyzed. The average age of patients was 40.0 ± 20 yr, and 335 (36.9%) patients were men. Among the elements that did not change over time were the facts that suicide was the most common cause, that alcohol consumption was involved in roughly 1 of 4 cases, and that there were more women than men. Furthermore, acetaminophen and doxylamine remained the most common poisoning agents. In conclusion, the average patient age and psychotic drug poisoning has increased over time, and the use of lavage treatment has decreased.

  13. Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii

    Energy Technology Data Exchange (ETDEWEB)

    Sparling, D.W. [Cooperative Wildlife Research Laboratory, Department of Zoology and Center for Ecology, Southern Illinois University, LS II, MS6504, Carbondale, IL 62901 (United States)]. E-mail: dsparl@siu.edu; Fellers, G. [Western Ecology Research Center, U.S. Geological Survey, Point Reyes National Seashore, Point Reyes, CA 94956 (United States)

    2007-06-15

    Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24 h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations. - Laboratory tests on the toxicity of OP insecticides and their oxons suggest that they may be acutely lethal to amphibians at ecologically relevant concentrations.

  14. Comparative 28-day repeated oral toxicity of Longdan Xieganwan, Akebia trifoliate (Thunb.) koidz., Akebia quinata (Thunb.) Decne. and Caulis aristolochiae manshuriensis in mice.

    Science.gov (United States)

    Xue, Xiang; Xiao, Ying; Gong, Likun; Guan, Shuhong; Liu, Yongzhen; Lu, Henglei; Qi, Xinming; Zhang, Yunhai; Li, Yan; Wu, Xiongfei; Ren, Jin

    2008-09-02

    Longdan Xieganwan, which contains Aristolochia species, is a traditional Chinese prescription. It has been used for thousands of years to "enhance liver". However, many cases of Longdan Xieganwan induced nephropathy were reported recently. This study was designed to compare the possible toxic effects of Longdan Xieganwan and three different Aristolochia species, i.e. Akebia trifoliate (Thunb.) koid (Akebia trifoliate), Akebia quinata (Thunb.) Decne. (Akebia quinata) and Caulis aristolochiae manshuriensis (Aristolochia manshuriensis). Mice were orally administered these drugs for 28 days. Clinical signs, body weights, serum biochemistry, organ weights and histopathology were examined. Significantly decreased body weights and obvious nephropathy were noticed in the Aristolochia manshuriensis groups at doses higher than 0.24 g/kg/d. A few endothelial cell degenerations in renal glomerulus were observed in the Akebia trifoliate group at a high-dose of 2.00 g/kg/d. No significant changes were observed in the other groups. The no-observed-adverse-effect levels (NOAELs) for Aristolochia manshuriensis, Akebia trifoliate, Akebia quinata and Longdan Xieganwan in this study for mice were 0.06 g/kg/d, 0.40 g/kg/d, higher than 3.00 g/kg/d and higher than 10.00 g/kg/d, which were equivalent to 0.25 times, 5 times, 25 times and 10 times of normal human dose in clinical prescription, respectively.

  15. A STUDY OF EFFICACY AND SAFETY OF TACROLIMUS COMPARED WITH CYCLOSPORIN A MICROEMULSION IN RENAL TRANSPLANTATION

    National Research Council Canada - National Science Library

    Jayakumar Edathedathe Krishnan; Noushad Thekke Puthiyottil; Sreelatha Melemadathil

    2016-01-01

    BACKGROUND The aim of this retrospective study was to compare therapeutic efficacy and safety profile of Cyclosporin and Tacrolimus in posttransplant patients with respect to graft function and metabolic disorders...

  16. Chronic toxicity of five structurally diverse demethylase-inhibiting fungicides to the crustacean Daphnia magna: a comparative assessment.

    Science.gov (United States)

    Hassold, Enken; Backhaus, Thomas

    2009-06-01

    Demethylase inhibitors (DMIs) are broad-spectrum fungicides that are ubiquitously used in agriculture and medicine. They comprise chemically heterogeneous substances that share a common biochemical target in fungi, the inhibition of a specific step in sterol biosynthesis. Several DMIs are suspected to disrupt endocrine-mediated processes in a range of organisms and to inhibit ecdysteroid biosynthesis in arthropods. It is unclear, however, whether and, if so, to what extent different DMI fungicides have a similar mode of action in nontarget organisms, which in turn would lead to a common chronic toxicity profile. Therefore, we selected a representative of each of the major DMI classes--the piperazine triforine, the pyrimidine fenarimol, the pyridine pyrifenox, the imidazole prochloraz, and the triazole triadimefon--and comparatively investigated their chronic toxicity to Daphnia magna. No toxicity was detectable up to the limit of solubility of triforine (61 micromol/L). All other DMIs reduced reproductive success by delaying molting and development and by causing severe developmental abnormalities among offspring. Prochloraz was most toxic (median effective concentration [EC50] for fecundity reduction, 0.76 micromol/L), followed by fenarimol (EC50, 1.14 micromol/L), pyrifenox (EC50, 3.15 micromol/L), and triadimefon (EC50, 5.13 micromol/L). Mean effect concentrations for fecundity reduction were related to lipophilicity and followed baseline toxicity. However, triadimefon and fenarimol (but none of the other tested DMIs) caused severe eye malformations among exposed offspring. Affected neonates did survive, but a reduced ecological fitness can be assumed. Offspring exposed to fenarimol in mater matured earlier. The investigated different life-history parameters were affected in a substance-specific manner. These qualitatively different toxicity profiles suggest additional, substance-specific mechanisms of action in D. magna that probably are related to an

  17. NHP or SIP : a comparative study in renal insufficiency associated anemia

    NARCIS (Netherlands)

    Essink-Bot, M L; Krabbe, P F; van Agt, H M; Bonsel, G J

    1996-01-01

    In this study we compared the feasibility, internal structure and psychometric characteristics (internal consistency, test-retest reliability, construct validity) of two widely used generic health status measures, i.e. the Nottingham Health Profile (NHP) and the Sickness Impact Profile (SIP) when em

  18. Characterization of Small Focal Renal Lesions: Diagnostic Accuracy with Single-Phase Contrast-enhanced Dual-Energy CT with Material Attenuation Analysis Compared with Conventional Attenuation Measurements.

    Science.gov (United States)

    Marin, Daniele; Davis, Drew; Roy Choudhury, Kingshuk; Patel, Bhavik; Gupta, Rajan T; Mileto, Achille; Nelson, Rendon C

    2017-09-01

    Purpose To determine whether single-phase contrast material-enhanced dual-energy material attenuation analysis improves the characterization of small (1-4 cm) renal lesions compared with conventional attenuation measurements by using histopathologic analysis and follow-up imaging as the clinical reference standards. Materials and Methods In this retrospective, HIPAA-compliant, institutional review board-approved study, 136 consecutive patients (95 men and 41 women; mean age, 54 years) with 144 renal lesions (111 benign, 33 malignant) measuring 1-4 cm underwent single-energy unenhanced and contrast-enhanced dual-energy computed tomography (CT) of the abdomen. For each renal lesion, attenuation measurements were obtained; attenuation change of greater than or equal to 15 HU was considered evidence of enhancement. Dual-energy attenuation measurements were also obtained by using iodine-water, water-iodine, calcium-water, and water-calcium material basis pairs. Mean lesion attenuation values and material densities were compared between benign and malignant renal lesions by using the two-sample t test. Diagnostic accuracy of attenuation measurements and dual-energy material densities was assessed and validated by using 10-fold cross-validation to limit the effect of optimistic bias. Results By using cross-validated optimal thresholds at 100% sensitivity, iodine-water material attenuation images significantly improved specificity for differentiating between benign and malignant renal lesions compared with conventional enhancement measurements (93% [103 of 111]; 95% confidence interval: 86%, 97%; vs 81% [90 of 111]; 95% confidence interval: 73%, 88%) (P = .02). Sensitivity with iodine-water and calcium-water material attenuation images was also higher than that with conventional enhancement measurements, although the difference was not statistically significant. Conclusion Contrast-enhanced dual-energy CT with material attenuation analysis improves specificity for

  19. Comparative toxicity of cis-cypermethrin in rainbow trout, frog, mouse, and quail.

    Science.gov (United States)

    Edwards, R; Millburn, P; Hutson, D H

    1986-07-01

    The synthetic alpha-cyano-phenoxybenzyl-containing pyrethroid insecticides act on the CNS of vertebrates and show a species-selective toxicity in the order fish greater than amphibians much greater than mammals greater than birds. Concentrations of [14C]cis-cypermethrin in the brains of representative members of each of these classes of chordates were measured at toxic signs (an onset of hyperactivity followed by seizures and loss of balance/equilibrium) as an indicator of target organ sensitivity. The concentration of cis-cypermethrin in brain, associated with toxic signs, in micrograms per gram (mean +/- SE) as determined by high-performance liquid chromatography was 0.08 +/- 0.03 (frog), 0.23 +/- 0.05 (trout), 1.71 +/- 0.33 (mouse), and 3.94 +/- 0.88 (quail). Trout brain was equally sensitive to the cis and trans isomers of cypermethrin. In both mouse and quail, some 90% of the radioactivity in the brain was parent pyrethroid. Trout and frog, however, afforded only 56 and 32%, respectively, of the brain 14C as cypermethrin, with the remaining radioactivity in both extractable and nonextractable metabolites, including 4'-hydroxy-cis-cypermethrin, which is potentially neuroactive. Following oral administration, cis-cypermethrin was readily absorbed and metabolized by quail. Intestinal uptake was far less rapid in trout and mouse, with unchanged cypermethrin dispersed in secreted bile, being readily eliminated from the intestines of fish. The uptake and metabolism of cis-cypermethrin and the brain sensitivities of these animals to the pyrethroid account for the observed differences in acute toxicity.

  20. Glutaraldehyde Treatment Elicits Toxic Response Compared to Decellularization in Bovine Pericardium

    OpenAIRE

    Umashankar, P.R.; Mohanan, P. V.; Kumari, T.V.

    2012-01-01

    Glutaraldehyde-stabilized bovine pericardium is used for clinical application since 1970s because of its desirable features such as less immunogenicity and acceptable durability. However, a propensity for calcification is reported on account of glutaraldehyde treatment. In this study, commercially available glutaraldehyde cross-linked bovine pericardium was evaluated for its in vitro cytotoxic effect, macrophage activation, and in vivo toxic response in comparison to decellularized bovine per...

  1. Effect of short-term high-protein compared with normal-protein diets on renal hemodynamics and associated variables in healthy young men.

    Science.gov (United States)

    Frank, Helga; Graf, Julia; Graf, Juliane; Amann-Gassner, Ulrike; Bratke, Renate; Daniel, Hannelore; Heemann, Uwe; Hauner, Hans

    2009-12-01

    High-protein diets are effective for weight reduction; however, little is known about the potential adverse renal effects of such diets. The aim of our study was to compare the effect of a high-protein (HP) with a normal-protein (NP) diet on renal hemodynamics and selected clinical-chemical factors. We prospectively studied the effect of an HP diet (2.4 g x kg(-1) x d(-1)) with that of an NP diet (1.2 g x kg(-1) x d(-1)) on the glomerular filtration rate (assessed on the basis of sinistrin-an inulin analog-clearance) and renal plasma flow (para-aminohippuric acid clearance) by using the constant infusion technique. Filtration fraction and renal vascular resistance were calculated. Twenty-four healthy young men followed the 2 diet protocols for 7 d each in a crossover design. They were individually advised by a dietitian to achieve the planned protein intake by selecting normal foods under isocaloric conditions. Serum and urinary variables and renal hemodynamics were measured on day 7 of both diets. The glomerular filtration rate (NP: 125 +/- 5 mL/min; HP: 141 +/- 8 mL/min; P < 0.001) and filtration fraction (NP: 23 +/- 5%; HP: 28 +/- 5%; P < 0.05) increased significantly with the HP diet. Renal plasma flow was not significantly different between the HP (496 +/- 25 mL/min) and NP (507 +/- 18 mL/min) phases. Renal vascular resistance was not significantly different between the NP (94 +/- 6 mm Hg x mL(-1) x min(-1)) and HP (99 +/- 8 mm Hg x mL(-1) x min(-1)) phases. Blood urea nitrogen, serum uric acid, glucagon, natriuresis, urinary albumin, and urea excretion increased significantly with the HP diet. A short-term HP diet alters renal hemodynamics and renal excretion of uric acid, sodium, and albumin. More attention should be paid to the potential adverse renal effects of HP diets.

  2. Renal Function Impairment and Associated Factors among HAART Naïve and Experienced Adult HIV Positive Individuals in Southwest Ethiopia: A Comparative Cross Sectional Study

    Science.gov (United States)

    Mekuria, Yewulsew; Yilma, Daniel; Mekonnen, Zeleke; Kassa, Tesfaye; Gedefaw, Lealem

    2016-01-01

    Background Human immunodeficiency virus (HIV) infection and its treatment cause renal diseases. Renal disease is associated with an increasing cause of morbidity and mortality in HIV positive individuals than in the general population. It has been also associated with adverse outcomes, such as complications of decreased renal functions and progression to renal failure. Objective To determine the prevalence and factors associated with renal function impairment among highly active antiretroviral therapy (HAART) naive and HAART experienced adult HIV positive individuals. Methods A facility based comparative cross-sectional study was conducted in Jimma University Specialized Hospital (JUSH) from June to September 2014. HIV positive individuals who visited JUSH during the study period were included in the study. Sociodemographic and clinical data were collected using a structured questionnaire. Blood specimen was analyzed for renal function tests. Descriptive statistics, Mann-Whitney U test and logistic regression analysis were done using SPSS version 16 software. Results A total of 446 HIV positive individuals, 223 HAART naïve and 223 HAART experienced, were recruited. The overall prevalence of renal function impairment was 18.2% [95%CI: 14.6–21.7]. The prevalence of renal impairment in HAART naive and HAART experienced persons was 28.7% [95%CI: 23.1–34.4] and 7.6% [95%CI: 4.6–11.6], respectively. Age ≥ 50 years (AOR = 3.6; 95% CI 1.4, 9.6), advanced WHO stage (AOR = 2.3; 95% CI 1.1, 4.7), and CD4 count <200 (AOR = 6.9; 95% CI 3.3, 14.2) were independent risk factors among HAART naive participants. Female gender (AOR = 6.6; 95 CI % 1.2, 34), age ≥ 50 years (AOR = 12.1; 95% CI 1.7, 84) and CD4 count <200 (AOR = 17; 95% CI 5.2, 58) were independent risk factors among HAART experienced participants. Conclusion The prevalence of renal function impairment was higher among HAART naïve than HAART experienced HIV positive individuals. Renal function impairment was

  3. Arsenic toxicity in mammals and aquatic animals: a comparative biochemical approach.

    Science.gov (United States)

    Ventura-Lima, Juliane; Bogo, Maurício Reis; Monserrat, José M

    2011-03-01

    Arsenic (As) is a widespread pollutant in the world and its toxicity is related to its chemical form, with inorganic forms being considered more toxic than the organic form, and huge differences in effects and processes of metabolism. This paper reviews the potential biochemical mechanisms of uptake of arsenic by aquaporins, capacity for metabolism and cellular efflux of As. It is known that As can affect signaling pathways since it can activate proteins such as ERK2, p38 and JNK, as shown in mammals. A comparison between phosphorylation sites of these proteins is presented in order to determine whether the same effect triggered by As in mammals might be observed in aquatic animals. The toxicity resulting from As exposure is considered to be linked to an imbalance between pro-oxidant and antioxidant homeostasis that results in oxidative stress. So, present review analyzes examples of oxidative stress generation by arsenic. Biotransformation of As is a process where firstly the arsenate is converted into arsenite and then transformed into mono-, di-, and trimethylated products. In the methylation process, the role of the omega isoform of glutathione-S-transferase (GST) is discussed. In addition, a phylogenetic tree was constructed for aquaporin proteins of different species, including aquatic animals, taking into account their importance in trivalent arsenic uptake.

  4. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Diane E. [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA (United States); Hoover, Benjamin [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Cloud, Loretta Grey [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Liu, Shihui [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Molinolo, Alfredo A. [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Leppla, Stephen H. [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Bugge, Thomas H., E-mail: thomas.bugge@nih.go [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  5. A Comparative Study on the Uptake and Toxicity of Nickel Added in the Form of Different Salts to Maize Seedlings

    Directory of Open Access Journals (Sweden)

    Jing Nie

    2015-11-01

    Full Text Available In soil ecotoxicological studies, a toxic metal is usually added in the form of either an inorganic or organic salt with relatively high solubility. Nitrate, chloride, acetate, or sulfate are commonly considered as valid options for that aim. However, recent studies have shown that different salts of the same metal at the same cationic concentration may exhibit different toxicities to plants and soil organisms. This information should be considered when selecting data to use for developing toxicological criteria for soil environment. A comparative study was carried out to evaluate the toxicity of five nickel (Ni salts: NiCl2, NiSO4, Ni(II-citrate, Ni(CH3COO2, and Ni(II-EDTA (ethylenediaminetetraacetate, on maize seedlings. The plant metrics used were plant height, shoot and root biomass, leaf soluble sugars and starch, and the Ni contents of the shoots and roots. The results indicated that when Ni was added to the soil, toxicity varied with the selected anionic partner with the following toxicity ranking NiSO4 < Ni(CH3COO2 < Ni(II-citrate < NiCl2 < Ni(II-EDTA. Taking the plant-height metric as an example, the effective concentrations for 50% inhibition (EC50 were 3148 mg·kg−1 for NiSO4, 1315 mg·kg−1 for NiCl2, and 89 mg·kg−1 for Ni(II-EDTA. Compared with the Ni in the other salts, that in Ni(II-EDTA was taken up the most efficiently by the maize roots and, thus, resulted in the greatest toxic effects on the plants. Nickel generally reduced leaf soluble sugars, which indicated an effect on plant carbohydrate metabolism. The outcome of the study demonstrates that different salts of the same metal have quite different ecotoxicities. Therefore, the anionic counterpart of a potentially toxic metal cation must be taken into account in the development of ecotoxicological criteria for evaluating the soil environment, and a preferred approach of leaching soil to reduce the anionic partner should also be considered.

  6. Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: Bevacizumab in combination with interferon-α2a compared with sunitinib

    NARCIS (Netherlands)

    G.H.J. Mickisch; M. Gore (Martin); B. Escudier (B.); G. Procopio (G.); S. Walzer (S.); M.J.C. Nuijten (Mark)

    2010-01-01

    textabstractBackground: Bevacizumab plus interferon-α2a (IFN) prolongs progression-free survival to>10 months, which is comparable with sunitinib as first-line treatment of metastatic renal cell carcinoma (RCC). The two regimens have different tolerability profiles; therefore, costs for managing

  7. Is there an advantage in performing a combined examination: diuretic renal scintigraphy and low dose computed tomography compared to the separate use of these methods in urolithiasis.

    Science.gov (United States)

    Hadzhiyska, Valeriya; Kostadinova, Irena; Demirev, Anastas

    2015-01-01

    Ultrasonography (US), radiography of the kidneys, ureters and bladder (RKUB), intravenous urography (IVU) and especially non-enchanced CT are well established diagnostic modalities in screening patients with urolithiasis, while not always fully diagnostic especially when obstructive uropathy or calculous pyelonephritis are present . Diuretic renal scintigraphy (DRS) can determine obstruction, may differentiate between complete or partial, acute or chronic obstruction, but can not specify the cause and often the location of obstruction. The imaging protocol, including DRS with technetium-99m-mercaptylacetyltriglycine ((99m)Tc-MAG3) and single photon emission tomography/computed tomography (SPET/CT) of the kidneys, ureters, and urinary bladder allows for both functional and morphological information, visualization of renal stones and possible renal complications. The main advantages and limitations of this combined examination are discussed and the test is compared to the separate use of DRS and low dose of CT, in urolithiasis.

  8. A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates

    DEFF Research Database (Denmark)

    Chen, Chen; Tang, Jiaqi; Dong, Wei;

    2007-01-01

    shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different......BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic...

  9. The mysid Siriella armata as a model organism in marine ecotoxicology: comparative acute toxicity sensitivity with Daphnia magna.

    Science.gov (United States)

    Pérez, Sara; Beiras, Ricardo

    2010-01-01

    Siriella armata (Crustacea, Mysidacea) is a component of the coastal zooplankton that lives in swarms in the shallow waters of the European neritic zone, from the North Sea to the Mediterranean. Juveniles of this species were examined as standard test organisms for use in marine acute toxicity tests. The effects of reference toxicants, three trace metals (Copper, Cadmium and Zinc), and one surfactant, sodium dodecyl sulfate (SDS) were studied on S. armata neonates (\\24 h) reared in the laboratory. Acute toxicity tests were carried out with filtered sea water on individual chambers (microplate wells for metals or glass vials for SDS) incubated in an isothermal room at 20 degrees C, with 16 h light: 8 h dark photoperiod for 96 h. Each neonate was fed daily with 10-15 nauplii of Artemia salina. Acute (96 h) LC50 values, in increasing order, were 46.9 lg/L for Cu, 99.3 lg/L for Cd, 466.7 lg/L for Zn and 8.5 mg/L for SDS. The LC(10), NOEC and LOEC values were also calculated. Results were compared with Daphnia magna, a freshwater cladoceran widely used as a standard ecotoxicological test organism. Acute (48 h) LC(50) values were 56.2 lg/L for Cu, 571.5 lg/L for Cd, 1.3 mg/L for Zn and 27.3 mg/L for SDS. For all the reference toxicants studied, the marine mysid Siriella armata showed higher sensitivity than the freshwater model organism Daphnia magna, validating the use of Siriella mysids as model organisms in marine acute toxicity tests.

  10. Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and non-resistant hypertension

    Science.gov (United States)

    Sim, John J.; Bhandari, Simran K.; Shi, Jiaxiao; Reynolds, Kristi; Calhoun, David A.; Kalantar-Zadeh, Kamyar; Jacobsen, Steven J.

    2015-01-01

    We sought to compare the risk of end stage renal disease (ESRD), ischemic heart event (IHE), congestive heart failure (CHF), cerebrovascular accident (CVA), and all-cause mortality among 470,386 individuals with resistant and nonresistant hypertension (non-RH). Resistant hypertension (60,327 individuals) was sub-categorized into 2 groups; 23,104 patients with cRH (controlled on 4 or more medicines) and 37,223 patients with uRH (uncontrolled on 3 or more medicines) in a 5 year retrospective cohort study. Cox proportional hazard modeling was used to estimate hazard ratios adjusting for age, gender, race, body mass index, chronic kidney disease (CKD), and co-morbidities. Resistant hypertension (cRH and uRH) compared to non-RH, had multivariable adjusted hazard ratios (95% confidence intervals) of 1.32 (1.27–1.37), 1.24 (1.20–1.28), 1.46 (1.40–1.52), 1.14 (1.10–1.19), and 1.06 (1.03–1.08) for ESRD, IHE, CHF, CVA, and mortality, respectively. Comparison of uRH to cRH had hazard ratios of 1.25 (1.18–1.33), 1.04 (0.99–1.10), 0.94 (0.89–1.01), 1.23 (1.14–1.31), and 1.01 (0.97–1.05) for ESRD, IHE, CHF, CVA, and mortality, respectively. Males and Hispanics had greater risk for ESRD within all 3 cohorts. Resistant hypertension had greater risk for ESRD, IHE, CHF, CVA, and mortality. The risk of ESRD and CVA and were 25% and 23% greater, respectively, in uRH compared to cRH supporting the linkage between blood pressure and both outcomes. PMID:25945406

  11. Comparing Heparin-Coated and Non-Coated Oxygenators on Renal Functions in Coronary Artery Bypass Surgery

    Directory of Open Access Journals (Sweden)

    Bektaş Battaloğlu

    2011-04-01

    Full Text Available Background: Renal damage and subsequent acute renal failure is one of the most important complications in patients who had cardiac surgery. Multicenter studies with thousands of patients which exposed the risk factors for acute renal failure has been published especially in the last decade. This study is designed for evaluation of heparin-coated and non-coated oxygenators on the renal functions. Methods: This study has been performed prospectively with 50 patients who had undergone coronary bypass surgery in our clinic from March 2006 to September 2006. The patients have been divided into two groups as non-coated oxygenators (n = 25, Group 1 used and heparin-coated oxygenators (n = 25, Group 2 used. Blood samples were collected at the preoperative, and at 1st, 24th and 96th postoperative hours. The demographic data were similar in two groups. Results: There was no early mortality in both groups. Operative and postoperative parameters were similar in both groups. There were no statistical differences between the evaluated parameters like BUN, creatinine, sodium, potassium, calcium, chloride, phosphorus, urine protein, creatinine clearence, urine sodium, urine calcium and urine chloride tests at preoperative period in both groups. We did not detect renal dysfunction in any patients. There are no statistical differences in the creatinine clearance in preoperative and postoperative periods in both groups. In group one, creatinin levels were lower than group two at 24 hours after surgery and these differences were statistically important in two groups. We found no significant difference between two groups regarding the other parameters for renal function during the postoperative period. Conclusion: In this study, there were not any significant difference between coated and non-coated oxygenators’ effects over renal functions of patients whose renal functions were normal preoperatively.

  12. Toxic myopathies.

    Science.gov (United States)

    Pasnoor, Mamatha; Barohn, Richard J; Dimachkie, Mazen M

    2014-08-01

    Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, because they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features, and possible underlying cellular mechanisms.

  13. Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: A comparative prospective clinical trial.

    Science.gov (United States)

    de Souza, Camila M; Tardelli, Maria A; Tedesco, Helio; Garcia, Natalia N; Caparros, Mario P; Alvarez-Gomez, Jose A; de Oliveira Junior, Itamar S

    2015-10-01

    Renal failure affects the pharmacology of nondepolarizing neuromuscular blockers making recovery of neuromuscular function unpredictable. Sugammadex antagonises rocuronium-induced neuromuscular blockade by encapsulating rocuronium, creating a stable complex molecule that is mainly excreted by the kidneys. Previous studies suggest that sugammadex is effective in reversing moderate neuromuscular block in the presence of renal failure, but no data are available regarding reversal of profound neuromuscular block in patients with renal failure. The objective of this study is to compare the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in patients with end-stage renal disease and those with normal renal function. A prospective clinical trial. Two university hospitals, from 1 October 2011 to 31 January 2012. Forty patients undergoing kidney transplant: 20 with renal failure [creatinine clearance (ClCr) 90 ml min). Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) stimulation. Profound neuromuscular block (posttetanic count, one to three responses) was maintained during surgery. Sugammadex 4 mg kg was administered on completion of skin closure. Recovery of the TOF ratio to 0.9 was recorded. Monitoring of neuromuscular function continued in the postanesthesia care unit for a further 2 h. The efficacy of sugammadex was evaluated by the time taken for the TOF ratio to recover to 0.9. The safety of sugammadex was assessed by monitoring for recurrence of neuromuscular block every 15 min for 2 h. Secondary variables were time to recovery of TOF ratio to 0.7 and 0.8. After sugammadex administration, the mean time for recovery of the TOF ratio to 0.9 was prolonged in the renal failure group (5.6 ± 3.6 min) compared with the control group (2.7 ± 1.3 min, P = 0.003). No adverse events or evidence of recurrence of neuromuscular block were observed. In patients with

  14. Comparative Cytogenetic Study on the Toxicity of Magnetite and Zinc Ferrite Nanoparticles in Sunflower Root Cells

    Science.gov (United States)

    Foca-nici, Ecaterina; Capraru, Gabriela; Creanga, Dorina

    2010-12-01

    In this experimental study the authors present their results regarding the cellular division rate and the percentage of chromosomal aberrations in the root meristematic cells of Helianthus annuus cultivated in the presence of different volume fractions of magnetic nanoparticle suspensions, ranging between 20 and 100 microl/l. The aqueous magnetic colloids were prepared from chemically co-precipitated ferrites coated in sodium oleate. Tissue samples from the root meristeme of 2-3 day old germinated seeds were taken to prepare microscope slides following Squash method combined with Fuelgen techniques. Microscope investigation (cytogenetic tests) has resulted in the evaluation of mitotic index and chromosomal aberration index that appeared diminished and respectively increased following the addition of magnetic nanoparticles in the culture medium of the young seedlings. Zinc ferrite toxic influence appeared to be higher than that of magnetite, according to both cytogenetic parameters.

  15. Fluoride-induced chronic renal failure.

    Science.gov (United States)

    Lantz, O; Jouvin, M H; De Vernejoul, M C; Druet, P

    1987-08-01

    Renal fluoride toxicity in human beings is difficult to assess in the literature. Although experimental studies and research on methoxyflurane toxicity have shown frank renal damage, observations of renal insufficiency related to chronic fluoride exposure are scarce. We report a case of fluoride intoxication related to potomania of Vichy water, a highly mineralized water containing 8.5 mg/L of fluoride. Features of fluoride osteosclerosis were prominent and end-stage renal failure was present. The young age of the patient, the long duration of high fluoride intake, and the absence of other cause of renal insufficiency suggest a causal relationship between fluoride intoxication and renal failure.

  16. Eight-year results of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation.

    Science.gov (United States)

    Gatault, Philippe; Bertrand, Dominique; Büchler, Matthias; Colosio, Charlotte; Hurault de Ligny, Bruno; Weestel, Pierre-François; Rerolle, Jean-Philippe; Thierry, Antoine; Sayegh, Johnny; Moulin, Bruno; Snanoudj, Renaud; Rivalan, Joseph; Heng, Anne-Elisabeth; Sautenet, Bénédicte; Lebranchu, Yvon

    2016-01-01

    We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus. © 2015 Steunstichting ESOT.

  17. Effectiveness of pharmacist dosing adjustment for critically ill patients receiving continuous renal replacement therapy: a comparative study.

    Science.gov (United States)

    Jiang, Sai-Ping; Zhu, Zheng-Yi; Wu, Xiao-Liang; Lu, Xiao-Yang; Zhang, Xing-Guo; Wu, Bao-Hua

    2014-01-01

    The impact of continuous renal replacement therapy (CRRT) on drug removal is complicated; pharmacist dosing adjustment for these patients may be advantageous. This study aims to describe the development and implementation of pharmacist dosing adjustment for critically ill patients receiving CRRT and to examine the effectiveness of pharmacist interventions. A comparative study was conducted in an intensive care unit (ICU) of a university-affiliated hospital. Patients receiving CRRT in the intervention group received specialized pharmacy dosing service from pharmacists, whereas patients in the no-intervention group received routine medical care without pharmacist involvement. The two phases were compared to evaluate the outcome of pharmacist dosing adjustment. The pharmacist carried out 233 dosing adjustment recommendations for patients receiving CRRT, and 212 (90.98%) of the recommendations were well accepted by the physicians. Changes in CRRT-related variables (n=144, 61.81%) were the most common risk factors for dosing errors, whereas antibiotics (n=168, 72.10%) were the medications most commonly associated with dosing errors. Pharmacist dosing adjustment resulted in a US$2,345.98 ICU cost savings per critically ill patient receiving CRRT. Suspected adverse drug events in the intervention group were significantly lower than those in the preintervention group (35 in 27 patients versus [vs] 18 in eleven patients, Pdosing adjustment, which was 8.93 days vs 7.68 days (P=0.26) and 30.10% vs 27.36% (P=0.39), respectively. Pharmacist dosing adjustment for patients receiving CRRT was well accepted by physicians, and was related with lower adverse drug event rates and ICU cost savings. These results may support the development of strategies to include a pharmacist in the multidisciplinary ICU team.

  18. Adverse Renal Effects of Novel Molecular Oncologic Targeted Therapies: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Kenar D. Jhaveri

    2017-01-01

    Full Text Available Novel targeted anti-cancer therapies have resulted in improvement in patient survival compared to standard chemotherapy. Renal toxicities of targeted agents are increasingly being recognized. The incidence, severity, and pattern of renal toxicities may vary according to the respective target of the drug. Here we review the adverse renal effects associated with a selection of currently approved targeted cancer therapies, directed to EGFR, HER2, BRAF, MEK, ALK, PD1/PDL1, CTLA-4, and novel agents targeted to VEGF/R and TKIs. In summary, electrolyte disorders, renal impairment and hypertension are the most commonly reported events. Of the novel targeted agents, ipilumumab and cetuximab have the most nephrotoxic events reported. The early diagnosis and prompt recognition of these renal adverse events are essential for the general nephrologist taking care of these patients.

  19. A comparative study on the relationship between acetylcholinesterase activity and acute toxicity in Daphnia magna exposed to anticholinesterase insecticides.

    Science.gov (United States)

    Printes, Liane Biehl; Callaghan, Amanda

    2004-05-01

    Acetylcholinesterase (AChE) activity was measured in Daphnia magna that had been exposed to four organophosphates (OPs; parathion, chlorpyrifos, malathion, and acephate) and one carbamate (propoxur) for 48 h. These results were related to acute toxicity (median effective concentration [EC50] for immobility). For the four OPs, the EC50s were 7.03 pM, 3.17 pM, 10.56 pM, and 309.82 microM, respectively. The EC50 for propoxur was 449.90 pM. Reduction in AChE activity was directly related to an increase in immobility in all chemicals tested. However, the ratio between the EC50 and the AChE median inhibiting concentration ranged from 0.31 to 0.90. A 50% reduction in AChE activity generally was associated with detrimental effects on mobility. However, for acephate, high levels of AChE inhibition (70%) were observed in very low concentrations and were not associated with immobility. In addition, increasing the concentration of acephate further had a slight negative effect on AChE activity but a strong detrimental effect on mobility. Binding sites other than AChE possibly are involved in acephate toxicity to D. magna. Our findings demonstrate different associations between AChE inhibition and toxicity when different chemicals are compared. Therefore, the value of using AChE activity as a biomarker in D. magna will be dependent on the chemical tested.

  20. Comparative acute toxicity of local detergents (Omo and Ariel on fingerlings of the Clarias gariepinus♀ x Heterobranchus longifilis♂ hybrid

    Directory of Open Access Journals (Sweden)

    Christopher B. Ndome

    2013-07-01

    Full Text Available The acute toxicity of local detergents - Omo detergent (Unilever Nigeria Plc. and Arieldetergent (Procter & Gamble Nigeria Limited - were compared using fingerlings of Clarias gariepinus ♀ xHeterobranchus longifilis ♂ hybrid (Heteroclarias, in a 96 hour bioassay. After a series of range findingtests, the fishes were exposed to concentrations of 0.00 ppm, 20 ppm, 30ppm, 40 ppm, 45 ppm and 50ppm of each detergent for 96 hours. The Median Lethal Concentrations (LC50 values for the detergentsranged between 33.03–35.19 ppm and 37.43–39.79 ppm for Omo and Ariel, respectively. Manifestationtimes decreased from 62–14 and 70–14 hours; overturning times decreased from 80–16 and 92–20hours, while survival times decreased from 96–17 and 96–23 hours for Omo and Ariel, respectively, withincreasing concentrations of the toxicants. Respiratory disturbances, loss of righting balance, lethargyand sudden fish death were observed in the exposed fishes. There was a strong concentration-mortalityrelationship for toxicants, yielding a strong positive correlation co-efficient, r2, of 0.9925 and 0.9882,respectively for Omo and Ariel detergents. The t-test analysis showed significant difference (p 0.05 recorded in other concentrations. There were no significant differences (p > 0.05in overturning and survival times of Omo and Ariel detergents in all the concentrations. The presentstudy shows that Omo detergent with a lesser mean LC50 value of 34.11 ± 1.08 could be more toxic thanAriel with a mean LC50 value of 36.66 ± 1.1. Although there was no statistically significant deferencebetween their LC50s (p > 0.05, it was concluded that effluents containing these detergents must not bedischarged indiscriminately into water bodies in order to avoid harm to fish and other aquatic life.

  1. Sediment toxicity screening with cost-effective microbiotests and conventional assays: A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Vanciheluwe, M.L.; Janssen, C.R.; Persoone, G. [Univ. of Ghent (Belgium). Lab. for Biological Research in Aquatic Pollution

    1995-12-31

    A large monitoring study of freshwater sediments, using the TRIAD approach, was conducted in Flanders (Belgium). This paper reports on the results of the toxicity assessment of 80 sediment samples evaluated with a battery of microbiotests and conventional assays. Sediment pore waters, extracted by squeezing, were tested with the Microtox{reg_sign} (Vibrio fischerii) and Thamnotoxkit{trademark} F (Thamnocephalus platyurus) microbiotests and the conventional (acute) assays with algae (Selenastrum capricornutum) and daphnids (Daphnia magna). A newly developed 5 day ELS test with the catfish Clarias gariepinus was also applied to the pore waters. Solid-phase testing was performed with the Microtox Sp{reg_sign} assay and the 10 day tests with Chironomus riparius and Hyalella azteca. Uni- and multivariate statistical techniques were applied to the data matrix to select a minimal test battery from the water phase and solid phase assays and from all tests combined. The influence of sediment associated confounding factors on the validity of the test results obtained with the various assays will be discussed. Finally a comparison of the predictive power of the selected battery of signal tests and that of the complete battery will be made and the potential use of the minimal battery for the initial hazard assessment of contaminated sediments will be reviewed.

  2. No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients.

    Science.gov (United States)

    Hansen, J M; Løkkegaard, H; Høy, C E; Fogh-Andersen, N; Olsen, N V; Strandgaard, S

    1995-01-01

    Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

  3. Comparing Cystatin C Changes as a Measure of Renal Function Before and After Radiotherapy in Patients with Stomach Cancer

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    Ahmad Ameri

    2012-01-01

    Full Text Available The objective of this study was to determine and compare Cystatin C changes before and after radiotherapy in patients with stomach cancer who were candidate for radiotherapy. This study was conducted as a prospective cohort one. Eighteen patients with definite diagnosis of stomach cancer under treatment by radiotherapy who presented to Radiotherapy-Oncology Center of Imam Hossein Hospital, Tehran-Iran, and the treatment in all cases was simultaneous chemoradiation with Xeloda were included. In all patients before radiotherapy and after radiotherapy serum creatinine (Cr and Cystatin C were measured simultaneously. Mean cystatin level before treatment (1.2±0.4 was significantly lower than that of post-treatment (1.6±0.36, (P=0.001. Serum Cr level before treatment was 1.15±0.33 and after radiotherapy was 1.08±0.24 and did not show significant difference. Glomerular filtration rate (GFR of the patients before radiotherapy was -46.8 ± 21.0 and after radiotherapy was 43.8±15.8 that did not have significant difference (P=0.146 and also blood urea nitrogen (BUN before radiotherapy was 20.72±3.7 and 20 ± 6.38 after radiotherapy that did not have significant difference (P=0.6. Comparison of the Cystatin C difference with total radiation dose of the kidneys that are put in three dose groups in radiotherapy field had association that in dose of less that 18 gray (Gy the Cystatin C change showed significant and positive association (P=0.027; r=0.52 and about 18-24 Gy the Cystatin C difference showed significant and negative association (P=0.023, r=-0.53. It seems that for evaluating the renal function, serum Cystatin C measurement is preferable than serum Cr. level.

  4. Chemoembolization of unresectable hepatocellular carcinoma: Decreased toxicity with slow-release doxorubicin‑eluting beads compared with lipiodol.

    Science.gov (United States)

    Recchia, Francesco; Passalacqua, Giovanni; Filauri, Pietro; Doddi, Marco; Boscarato, Pietro; Candeloro, Giampiero; Necozione, Stefano; Desideri, Giovambattista; Rea, Silvio

    2012-05-01

    Chemoembolization with lipiodol (TACE) improves survival of selected patients with unresectable hepatocellular carcinoma (HCC), but results in substantial toxicity. To improve treatment tolerance, we conducted this phase II study using doxorubicin-loaded beads (DC Beads®) delivered by selective transcatheter arterial chemoembolization (DEB-TACE). We compared the results with those obtained with TACE in our historical controls. Thirty-five patients were recruited with diagnoses of HCC. Patients received DEB-TACE with doxorubicin loaded on DC Beads. Computed tomography of the upper abdomen was performed one month after DEB-TACE. Historical controls were a group of 70 patients with matched characteristics treated with TACE. After a median follow-up of 14.1 months (range, 6-36 months), 22 patients (63%) had an objective response. There was a statistically significant decrease in liver enzymes (p<0.001), lactate dehydrogenase, (p<0.001) in DEB-TACE-treated patients compared to TACE-treated patients. DEB-TACE with doxorubicin-loaded DC Beads, a safe and reliable treatment for HCC, leads to decreased toxicity compared to TACE.

  5. NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction

    Energy Technology Data Exchange (ETDEWEB)

    Wennberg, Berit M.; Baumann, Pia; Gagliardi, Giovanna (Dept. of Medical Physics, Karolinska Univ. Hospital and the Karolinska Inst., Stockholm (Sweden)), e-mail: berit.wennberg@karolinska.se (and others)

    2011-05-15

    Background. In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. Material and methods. Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman- Kutcher-Burman (LKB) model. In the LQ-correction alpha/beta = 3 Gy was used and the USC parameters used were: alpha/beta = 3 Gy, D{sub 0} = 1.0 Gy, n = 10, alpha 0.206 Gy-1 and d{sub T} = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether 'high doses to small volumes' or 'low doses to large volumes' are most important for lung toxicity. Results and Discussion. NTCP analysis with the LKB-model using parameters m = 0.4, D50 = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D{sub 50} = 20 Gy n = 0.93 with LQ correction and n 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ,USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling

  6. A comparative study of the acute toxicity of the herbicide atrazine to cladocerans Daphnia magna, Ceriodaphnia silvestrii and Macrothrix flabelligera

    Directory of Open Access Journals (Sweden)

    Raquel Aparecida Moreira

    2014-03-01

    Full Text Available AIM: In this study we compared the sensitivity of three species of Cladocera, Daphnia magna, Ceriodaphnia silvestrii and Macrothrix flabelligera, to the commercial product of the herbicide Atrazine, the Atrazine Atanor 50 SC® (500 g/L, widely used on crops in Brazil. METHODS: Acute toxicity tests were performed at the nominal atrazine concentrations 2.25, 4.5, 9.0, 18.0, 36 and 72 mg L-1, on C. silvestrii and M. flabelligera and at 2.25, 4.5, 9.0, 18.0, 36, 72 and 144 mg L-1 on D. magna. The range of concentrations tested was established in a series of preliminary tests. RESULTS: The toxicity tests showed that the two species naturally occurring in water bodies in Brazil were more susceptible than Daphnia magna. The effective concentrations of Atrazine Atanor 50 SC® (EC50- 48 h to the species M. flabelligera, C. silvestrii and D. magna were 12.37 ± 2.67 mg L-1, 14.30 ± 1.55 mg L-1 and 50.41 ± 2.64 mg L-1, respectively. Furthermore, when EC50 observed here for M. flabelligera and C. silvestrii were compared with published values of EC50 or LC50 (mg L-1 for various aquatic organisms exposed to atrazine, it was seen that these two cladocerans were the most sensitive to the herbicide. CONCLUSIONS: Considering these results and the broad distribution of C. silvestrii and M. flabelligera in tropical and subtropical regions, it is concluded that these native species would be valuable test organisms in ecotoxicological tests, for the monitoring of toxic substances in tropical freshwaters.

  7. Modulatory effects of methanol extract of Artocarpus altilis (Moraceae) on cadmium-induced hepatic and renal toxicity in male Wistar rats.

    Science.gov (United States)

    Adaramoye, Oluwatosin Adekunle; Akanni, Olubukola Oyebimpe

    2016-03-01

    Cadmium (Cd) is an environmental risk factor with an established toxicity in animals. Therefore, natural antioxidants may be protective against Cd-toxicity. The study was designed to investigate the modulatory effects of methanol extract of Artocarpus altilis (AA) on oxidant-antioxidant balance and lipid profile in liver and kidney of Cd-exposed rats while quercetin (QE) served as standard. Total phenolic content (TPC) and 2,2-diphenyl-1-picryldydrazyl (DPPH) radical scavenging activity of AA were assessed in vitro. In vivo, rats were orally treated with AA (200mg/kg) and QE (25mg/kg) daily for three weeks and challenged with two doses of Cd (1.5mg/kg, i.p.) in the last 72h. The TPC and DPPH scavenging effects of AA were high and comparable with catechin. Cd-intoxication significantly (paltilis protects against Cd-induced liver and kidney dysfunction via antioxidant and radical scavenging activities. Copyright © 2016. Published by Elsevier B.V.

  8. Effectiveness of pharmacist dosing adjustment for critically ill patients receiving continuous renal replacement therapy: a comparative study

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    Jiang SP

    2014-06-01

    Full Text Available Sai-Ping Jiang,1 Zheng-Yi Zhu,2 Xiao-Liang Wu,3 Xiao-Yang Lu,1 Xing-Guo Zhang,1 Bao-Hua Wu1 1Department of Pharmacy, the First Affiliated Hospital, 2Department of Pharmacy, Children’s Hospital, College of Medicine, Zhejiang University, Hangzhou, 3Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China Background: The impact of continuous renal replacement therapy (CRRT on drug removal is complicated; pharmacist dosing adjustment for these patients may be advantageous. This study aims to describe the development and implementation of pharmacist dosing adjustment for critically ill patients receiving CRRT and to examine the effectiveness of pharmacist interventions. Methods: A comparative study was conducted in an intensive care unit (ICU of a university-affiliated hospital. Patients receiving CRRT in the intervention group received specialized pharmacy dosing service from pharmacists, whereas patients in the no-intervention group received routine medical care without pharmacist involvement. The two phases were compared to evaluate the outcome of pharmacist dosing adjustment. Results: The pharmacist carried out 233 dosing adjustment recommendations for patients receiving CRRT, and 212 (90.98% of the recommendations were well accepted by the physicians. Changes in CRRT-related variables (n=144, 61.81% were the most common risk factors for dosing errors, whereas antibiotics (n=168, 72.10% were the medications most commonly associated with dosing errors. Pharmacist dosing adjustment resulted in a US$2,345.98 ICU cost savings per critically ill patient receiving CRRT. Suspected adverse drug events in the intervention group were significantly lower than those in the preintervention group (35 in 27 patients versus [vs] 18 in eleven patients, P<0.001. However, there was no significant difference between length of ICU stay and mortality after pharmacist dosing adjustment, which

  9. Clinical efficacy of Spasmofen® suppository in the emergency treatment of renal colic: a randomized, double-blind, double-dummy comparative trial

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    Yakoot M

    2014-05-01

    Full Text Available Mostafa Yakoot,1 Amel Salem,2 Sameh Yousef,2 Sherine Helmy31Green Clinic and Research Center, 2Alexandria Helmy Medical Center, 3Pharco Corporation, Alexandria, EgyptBackground: Renal colic is typically characterized by the sudden onset of severe pain radiating from the flank to the groin and its acute management in emergency departments essentially aims at rapid pain relief. Spasmofen® is a brand of Amriya Pharmaceutical Industries in the form of rectal suppositories containing ketoprofen 100 mg and hyoscine butylbromide 10 mg. This combination is intended for the rapid relief of severe colicky pain in the renal system, hepatobiliary system, or gastrointestinal tract. This trial aims to compare a single-dose of Spasmofen rectal suppository to a single intravenous (IV ketorolac tromethamine 30 mg/2 mL dose in patients with acute renal colic.Methods: A total of 80 eligible consecutive patients presenting to the emergency departments of two medical centers with acute renal colic were included in the study. Eligible patients who signed the informed consent were randomly assigned into two treatment groups: an experimental group (Spasmofen group who received one Spasmofen rectal suppository plus an IV injection of 2 mL of normal saline solution; and a control group (ketorolac group who received one ketorolac 30 mg/2 mL ampoule IV plus one placebo suppository. Treatment success, defined as a change in the verbal rating score from severe or moderate pain to none or mild at 60 minutes after the dose, was compared between groups using the chi-square/Fisher's exact test. Percentage reductions in visual pain analog scale (VPAS scores at 15 and 60 minutes after the dose were compared between groups using the Z-test for proportions.Results: Successful treatment at 60 minutes occurred in 35 of 40 (87.5% of Spasmofen-treated patients and in 33 of 40 (82.5% of ketorolac-treated patients. The difference was not statistically significant by Fisher's exact test

  10. A comparative study of artificial neural network and multivariate regression analysis to analyze optimum renal stone fragmentation by extracorporeal shock wave lithotripsy

    Directory of Open Access Journals (Sweden)

    Goyal Neeraj

    2010-01-01

    Full Text Available To compare the accuracy of artificial neural network (ANN analysis and multi-variate regression analysis (MVRA for renal stone fragmentation by extracorporeal shock wave lithotripsy (ESWL. A total of 276 patients with renal calculus were treated by ESWL during December 2001 to December 2006. Of them, the data of 196 patients were used for training the ANN. The predictability of trained ANN was tested on 80 subsequent patients. The input data include age of patient, stone size, stone burden, number of sittings and urinary pH. The output values (predicted values were number of shocks and shock power. Of these 80 patients, the input was analyzed and output was also calculated by MVRA. The output values (predicted values from both the methods were compared and the results were drawn. The predicted and observed values of shock power and number of shocks were compared using 1:1 slope line. The results were calculated as coefficient of correlation (COC (r2 . For prediction of power, the MVRA COC was 0.0195 and ANN COC was 0.8343. For prediction of number of shocks, the MVRA COC was 0.5726 and ANN COC was 0.9329. In conclusion, ANN gives better COC than MVRA, hence could be a better tool to analyze the optimum renal stone fragmentation by ESWL.

  11. Antibiotic managment in renal failure.

    Science.gov (United States)

    Winter, R E

    1976-06-01

    This is a brief compilation of the work of many investigators. It includes facts about toxicity and recommendations about antibiotic management in patients with renal failure. As new data are accrued, changes in these recommendations will be necessary.

  12. A comparative study of properties and toxic constituents of funnel web spider (Atrax) venoms.

    Science.gov (United States)

    Sheumack, D D; Baldo, B A; Carroll, P R; Hampson, F; Howden, M E; Skorulis, A

    1984-01-01

    The crude venoms of male and female Sydney funnel web spiders, Atrax robustus, were compared by cation-exchange and high-performance liquid chromatography, lethality to new-born mice, polyacrylamide gel isoelectric focusing, immunoelectrophoresis, phospholipase A analysis, effects on the mouse phrenic nerve hemidiaphragm and passive paw oedema in the rat and, except in the case of rat paw oedema, were found to exhibit quite different properties. Polyacrylamide gel isoelectric focusing and high-performance liquid chromatography proved to be suitable for gender and species determination when applied to the venoms of A. formidabilis, A. infensus, A. robustus and A. versutus. These venoms were also compared by lethality, promotion of muscle fasciculation and phospholipase A activity.

  13. Miringosclerose em pacientes com insuficiência renal crônica: análise comparativa com um grupo controle Myringosclerosis in patients with chronic renal failure: comparative analysis with a control group

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    Silvio Caldas Neto

    2008-08-01

    control individuals. The frequency of positive otoscopies was compared between the two groups, based on individual variables and those pertaining to CRF. RESULTS: 11.7% of the patients had a positive otoscopy in the CRF group, compared to 5.1% in the control group. There was no statistical diference in the frequency of myringosclerosis acording to gender, ethnic group, time of dialysis or serum minerals. The groups had a wide age range. CONCLUSION: Although the findings of this study suggest a higher ocurrence of myringosclerosis in patients with renal disease, they do not provide a basis for stating that there is any relation between renal failure and tympanic alterations.

  14. Comparative Toxicity Assessment of Nanosilver on Three Daphnia Species in Acute, Chronic and Multi-Generation Experiments

    Science.gov (United States)

    Völker, Carolin; Boedicker, Cathinka; Daubenthaler, Jan; Oetken, Matthias; Oehlmann, Jörg

    2013-01-01

    The antibacterial properties of nanosilver have led to a versatile application spectrum including medical purposes and personal care products. However, the increasing use of nanosilver has raised concerns about its environmental impacts. Long-term exposure studies with aquatic invertebrates are essential to assess possible adverse effects on aquatic ecosystems. In the present study, acute (48 h), chronic (21 d) and long-term effects of nanosilver (primary size 15 nm) on five successive generations of three Daphnia species (D. magna, D. pulex, and D. galeata) were investigated. Acute EC50 values of nanosilver were 121 µg Ag L−1 for D. magna being the least sensitive species and 8.95 and 13.9 µg Ag L−1 for D. pulex and D. galeata, respectively. Chronic exposure provided EC10 values of 0.92 µg Ag L−1 for D. magna showing the most sensitive chronic reaction and 2.25 and 3.45 µg Ag L−1 for D. pulex and D. galeata, respectively. Comparative exposure to AgNO3 revealed a generally higher toxicity of the soluble form of silver. The multi-generation experiments resulted in effects on the population level for all tested species. Exposure of D. magna indicated an increased toxicity of nanosilver in the fifth generation of animals exposed to 10 µg Ag L−1. Neonates from pre-exposed parental daphnids did not completely recover when transferred into clean water. Exposure of D. pulex and D. galeata revealed not only increasing toxicity in some generations, but also greater tolerance to nanosilver. This study contributes to the assessment of the risk potential of nanosilver on aquatic ecosystems. It shows that effects of nanosilver vary within one genus and change with exposure duration. Therefore, long-term studies considering different aquatic species are needed to better understand the possible effects of nanosilver on aquatic ecosystems. PMID:24116021

  15. Comparative toxicity of nano ZnO and bulk ZnO towards marine algae Tetraselmis suecica and Phaeodactylum tricornutum.

    Science.gov (United States)

    Li, Jiji; Schiavo, Simona; Rametta, Gabriella; Miglietta, Maria Lucia; La Ferrara, Vera; Wu, Changwen; Manzo, Sonia

    2017-03-01

    The wide use of ZnO nanoparticles in a number of products implies an increasing release into the marine environment, resulting in the need to evaluate the potential effects upon organisms, and particularly phytoplankton, being at the base of the throphic chain. To this aim, dose-response curves for the green alga Tetraselmis suecica and the diatom Phaeodactylum tricornutum derived from the exposure to nano ZnO (100 nm) were evaluated and compared with those obtained for bulk ZnO (200 nm) and ionic zinc. The toxic effects to both algae species were reported as no observable effect concentration (NOEC) of growth inhibition and as 1, 10, and 50% effect concentrations (EC1, EC10, and EC50). The toxicity decreased in the order nano ZnO > Zn(2+) > bulk ZnO. EC50 values for nano ZnO were 3.91 [3.66-4.14] mg Zn/L towards the green microalgae and 1.09 [0.96-1.57] mg Zn/L towards the diatom, indicating a higher sensitivity of P. tricornutum. The observed diverse effects can be ascribed to the interaction occurring between different algae and ZnO particles. Due to algae motility, ZnO particles were intercepted in different phases of aggregation and sedimentation processes, while algae morphology and size can influence the level of entrapment by NP aggregates.This underlines the need to take into account the peculiarity of the biological system in the assessment of NP toxicity.

  16. Acute pancreatitis, acute hepatitis and acute renal failure favourably resolved in two renal transplant recipients.

    Science.gov (United States)

    Voiculescu, Mihai; Ionescu, Camelia; Ismail, Gener; Mandache, Eugen; Hortopan, Monica; Constantinescu, Ileana; Iliescu, Olguta

    2003-03-01

    Renal transplantation is often associated with severe complications. Except for acute rejection, infections and toxicity of immunosuppressive treatment are the most frequent problems observed after transplantation. Infections with hepatic viruses (HBV, HDV, HCV, HGV) and cytomegalic virus (CMV) are the main infectious complications after renal transplantation. Cyclosporine toxicity is not unusual for a patient with renal transplantation and is even more frequent for patients with hepatic impairment due to viral infections. The subjects of this report are two renal transplant recipients with acute pancreatitis, severe hepatitis and acute renal failure on graft, receiving immunosuppressive therapy for maintaining renal graft function

  17. Comparative study of toxic effects of anatase and rutile type nanosized titanium dioxide particles in vivo and in vitro.

    Science.gov (United States)

    Numano, Takamasa; Xu, Jiegou; Futakuchi, Mitsuru; Fukamachi, Katsumi; Alexander, David B; Furukawa, Fumio; Kanno, Jun; Hirose, Akihiko; Tsuda, Hiroyuki; Suzui, Masumi

    2014-01-01

    Two types of nanosized titanium dioxide, anatase (anTiO2) and rutile (rnTiO2), are widely used in industry, commercial products and biosystems. TiO2 has been evaluated as a Group 2B carcinogen. Previous reports indicated that anTiO2 is less toxic than rnTiO2, however, under ultraviolet irradiation anTiO2 is more toxic than rnTiO2 in vitro because of differences in their crystal structures. In the present study, we compared the in vivo and in vitro toxic effects induced by anTiO2 and rnTiO2. Female SD rats were treated with 500 ?g/ml of anTiO2 or rnTiO2 suspensions by intra-pulmonary spraying 8 times over a two week period. In the lung, treatment with anTiO2 or rnTiO2 increased alveolar macrophage numbers and levels of 8-hydroxydeoxyguanosine (8-OHdG); these increases tended to be lower in the anTiO2 treated group compared to the rnTiO2 treated group. Expression of MIP1??mRNA and protein in lung tissues treated with anTiO2 and rnTiO2 was also significantly up-regulated, with MIP1??mRNA and protein expression significantly lower in the anTiO2 group than in the rnTiO2 group. In cell culture of primary alveolar macrophages (PAM) treated with anTiO2 and rnTiO2, expression of MIP1??mRNA in the PAM and protein in the culture media was significantly higher than in control cultures. Similarly to the in vivo results, MIP1??mRNA and protein expression was significantly lower in the anTiO2 treated cultures compared to the rnTiO2 treated cultures. Furthermore, conditioned cell culture media from PAM cultures treated with anTiO2 had less effect on A549 cell proliferation compared to conditioned media from cultures treated with rnTiO2. However, no significant difference was found in the toxicological effects on cell viability of ultra violet irradiated anTiO2 and rnTiO2. In conclusion, our results indicate that anTiO2 is less potent in induction of alveolar macrophage infiltration, 8-OHdG and MIP1??expression in the lung, and growth stimulation of A549 cells in vitro than rnTiO2.

  18. Regulatory perspectives of Type II prodrug development and time-dependent toxicity management: nonclinical Pharm/Tox analysis and the role of comparative toxicology.

    Science.gov (United States)

    Wu, Kuei-Meng; Farrelly, James G

    2007-07-01

    Many therapeutic agents are prepared in prodrug forms, which are classified into Type I, II and subtypes A, B based on their sites of conversion. Recently, an increasing number of INDs have appeared as Type II prodrugs that often contain dual tracks of toxicity profile exploration, one on the prodrug and another on the active drug. A comparative toxicology analysis is introduced here to assist reviewers to evaluate the dual toxicity profiles effectively. The analysis helps determine which toxicity is contributed by the prodrug itself, its intermediates, or the active drug itself. As prodrug INDs, or any other new molecular entity (NME) INDs progress into advanced phases of toxicology development, analysis of time-dependent component of toxicity expression, regarding the emergence of new target organs over time, becomes more significant. A strategy is developed to address Pharm/Tox issues such as what duration is required for a toxicity to emerge at the exposure level achieved or dose studied, how many animals in the group are affected, whether the toxicity is a cross-species phenomenon, and whether it is reversible, etc. In conclusion, dual-track comparative toxicology can be useful in the understanding of Type II prodrug's mechanism of toxicity, and that time-dependent toxicology analysis offers means to detecting new toxicity emergence over time. Both approaches could significantly facilitate secondary and tertiary review processes during IND development of a prodrug or NME.

  19. Investigation of recurrent deletion loci specific to conventional renal cell carcinoma by comparative allelotyping in major epithelial carcinomas

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    Rashmi R Bhat (Singh

    2012-01-01

    Full Text Available Objective: Loss of heterozygosity (LOH studies were undertaken to investigate the consistently deleted loci/? tumor suppressor gene loci (TSG on 3p in conventional renal cell carcinoma (cRCC. Materials and Methods: LOH studies were performed by polymerase chain reaction (PCR using 15 micro satellite markers mapped in region 3p12-p26 on 40 paired cRCC tumors and normal kidney at Stages I-IV. Simultaneously, fluorescent in-situ hybridization (FISH studies were performed to investigate the allelic deletion of fragile histidine triad (FHIT. Results: Our studies revealed three affected regions; 3p12.2-p14.1, 3p14.2-p21.1, and 3p24.2-p26.1 with differential frequencies in Group I (Stage I and II and Group II (Stage III and IV. Incidence for D3S1234 (FHIT locus and D3S2454 (3p13 was 75% and 83% in Group I and II, respectively. Comparative allelotyping in epithelial malignancies like lung, bladder, and breast tumors revealed LOH (frequency 14−20% only in breast tumors for D3S2406, D3S1766 (distal to FHIT, and D3S1560 (distal to VHL, Von-Hippal Lindau. FISH using FHIT gene probe revealed deletions in cRCC (88%, breast (30%, and lung tumors (10% with no deletions in bladder tumors and leukemias, signifying the importance of FHIT in the pathogenesis of tumors of epithelial origin. Conclusion: Our findings suggested FHIT deletion as an early and VHL deletion as an early and/or late event in cRCC. Additionally, studies also disclosed the recurrent deletions of flanking loci to FHIT and VHL in cRCC. The dilemma of interstitial or continuous deletion on 3p needs to be resolved by implementation of latest sensitive molecular techniques that would further help to narrow down search for TSG loci specific to cRCC, other than VHL and FHIT.

  20. Therapeutic trials in lupus nephritis. Problems related to renal histology, monitoring of therapy and measures of outcome.

    Science.gov (United States)

    Balow, J E

    1981-01-01

    Approaches to treatment of lupus nephritis have been complicated by controversies in the definitions of the types of renal histology, the relevance of immunological and renal monitoring techniques as therapeutic guidelines, and lack of definitive clinical trials. It is suggested that demonstration of the efficacy of various therapeutic agents in clinical trials may be identified earlier by renal histological changes and/or assessment of drug toxicity compared to the time required for differences based on renal functional changes to emerge as ultimate measures of outcome.

  1. Comparative toxicity of halogenated hydrocarbons: Molecular aspects. Final report, 1 January-31 December 1992

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, G.G.

    1993-07-13

    The comparative hepatotoxicities of perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA) and the tri-and tetra-oligomers of chloro-trifluoro ethylene (CTFE) have been investigated in the rat and guinea pig. All compounds have been identified as causing hepatomegaly, peroxisome proliferation and cytochrome P4504A1 induction in the rat. The guinea pig is non-responsive to these compounds and the observed liver changes appear to be specific to lower rodent species. The implications of this study are that the above compounds do not represent a health hazard to man.

  2. Comparative toxicities of aluminum and zinc from sacrificial anodes or from sulfate salt in sea urchin embryos and sperm.

    Science.gov (United States)

    Caplat, Christelle; Oral, Rahime; Mahaut, Marie-Laure; Mao, Andrea; Barillier, Daniel; Guida, Marco; Della Rocca, Claudio; Pagano, Giovanni

    2010-09-01

    The toxicity of aluminum or zinc from either sacrificial anodes (SA) or their sulfate salts (SS) was evaluated in sea urchin (Paracentrotus lividus) embryos or sperm exposed to Al(III) or Zn(II) (SA or SS, 0.1-10 microM), scoring developmental defects (DDs), fertilization rate (FR), and mitotic abnormalities. A significant DD increase was observed in SS, but not SA Al(III)- and Zn(II)-exposed embryos vs. controls. Both Al(III) and Zn(II), up to 10 microM, from SA and SS, inhibited mitotic activity and induced mitotic aberrations in exposed embryos. SA-Al(III)-exposed sperm displayed a significant FR increase, unlike Al(III) sulfate overlapping with controls. Both SA-Zn(II) and Zn(II) sulfate sperm exposure resulted in a significant FR increase. The offspring of SA-Al(III)-exposed sperm displayed a significant DD decrease, unlike Al(III) sulfate exposure. Zinc sulfate sperm exposure resulted in a significant increase in offspring DDs, whereas SA-Zn(II) sperm exposure decreased DDs. Together, exposures to SA-dissolved Al(III) or Zn(II) resulted in lesser, if any toxicity, up to hormesis, compared to SS. Studies of metal speciation should elucidate the present results.

  3. Comparative in vitro toxicity of nitrosamines and nitramines associated with amine-based carbon capture and storage.

    Science.gov (United States)

    Wagner, Elizabeth D; Osiol, Jennifer; Mitch, William A; Plewa, Michael J

    2014-07-15

    Amine-based CO2 capture is a prime contender for the first full-scale implementation of CO2 capture at fossil fuel-fired power plants postcombustion. However, the formation of potentially carcinogenic N-nitrosamines and N-nitramines from reactions of flue gas NOx with the amines presents a potential risk for contaminating airsheds and drinking water supplies. Setting regulatory emission limits is hampered by the dearth of toxicity information for the N-nitramines. This study employed quantitative in vitro bioassays for mutagenicity in Salmonella typhimurium, and chronic cytotoxicity and acute genotoxicity in Chinese hamster ovary (CHO) cells to compare the toxicity of analogous N-nitrosamines and N-nitramines relevant to CO2 capture. Although the rank order was similar for genotoxicity in CHO cells and mutagenicity in S. typhimurium, the Salmonella assay was far more sensitive. In general, mutagenicity was higher with S9 hepatic microsomal activation. The rank order of mutagenicity was N-nitrosodimethylamine (NDMA)>N-nitrosomorpholine>N-nitrodimethylamine>1,4-dinitrosopiperazine>N-nitromorpholine>1,4-dinitropiperazine>N-nitromonoethanolamine>N-nitrosodiethanolamine>N-nitrodiethanolamine. 1-Nitrosopiperazine and 1-nitropiperazine were not mutagenic. Overall, N-nitrosamines were ∼15-fold more mutagenic than their N-nitramine analogues.

  4. Organophosphate-pyrethroid combination pesticides may be associated with increased toxicity in human poisoning compared to either pesticide alone.

    Science.gov (United States)

    Iyyadurai, R; Peter, J V; Immanuel, S; Begum, A; Zachariah, A; Jasmine, S; Abhilash, K P P

    2014-06-01

    Organophosphate (OP) poisoning results in significant toxicity while pyrethroid poisoning is associated with extremely low fatality. OPs can inhibit the detoxification of pyrethroid and increase the toxicity of the combination. We assessed whether mixed OP-pyrethroid poisoning impacted outcome in human poisoning. Patients were identified from a prospectively collected institutional poisoning database that incorporates demographic and outcome data of patients presenting with poisoning. Of the 1177 poisoned patients admitted over 2 years, 32 presented with OP-pyrethroid (50% chlorpyrifos-5% cypermethrin mixture) poisoning (Group 1), 26 consumed 20% chlorpyrifos (Group 2), and 32 took 15% cypermethrin (Group 3). Seizures occurred in 15.6% (n = 5) with chlorpyrifos-cypermethrin poisoning, 18.8% (n = 6) with cypermethrin poisoning, and 3.9% (n = 1) with chlorpyrifos poisoning. Ventilatory requirements were 53.5% (17/32), 42.3% (11/26), and 15.7% (5/32) in Groups 1-3, respectively. Ventilator-free days (Mean ± SD) was significantly lower (p pesticides alone. Further studies are required comparing patients poisoned by formulations with similar quantities of OP and pyrethroid or with analysis of blood pesticide concentration on admission.

  5. Comparative toxicity of nanoparticulate/bulk Yb₂O₃ and YbCl₃ to cucumber (Cucumis sativus).

    Science.gov (United States)

    Zhang, Peng; Ma, Yuhui; Zhang, Zhiyong; He, Xiao; Guo, Zhi; Tai, Renzhong; Ding, Yayun; Zhao, Yuliang; Chai, Zhifang

    2012-02-01

    With the increasing utilization of nanomaterials, there is a growing concern for the potential environmental and health effects of them. To assess the environmental risks of nanomaterials, better knowledge about their fate and toxicity in plants are required. In this work, we compared the phytotoxicity of nanoparticulate Yb(2)O(3), bulk Yb(2)O(3), and YbCl(3)·6H(2)O to cucumber plants. The distribution and biotransformation of the three materials in plant roots were investigated in situ by TEM, EDS, as well as synchrotron radiation based methods: STXM and NEXAFS. The decrease of biomass was evident at the lowest concentration (0.32 mg/L) when exposed to nano-Yb(2)O(3), while at the highest concentration, the most severe inhibition was from YbCl(3). The inhibition was dependent on the actual amount of toxic Yb uptake by the cucumber plants. In the intercellular regions of the roots, Yb(2)O(3) particles and YbCl(3) were all transformed to YbPO(4). We speculate that the dissolution of Yb(2)O(3) particles induced by the organic acids exuded from roots played an important role in the phytotoxicity. Only under the nano-Yb(2)O(3) treatment, YbPO(4) deposits were found in the cytoplasm of root cells, so the phytotoxicity might also be attributed to the Yb internalized into the cells.

  6. Trauma renal Renal trauma

    Directory of Open Access Journals (Sweden)

    Gerson Alves Pereira Júnior

    1999-02-01

    Full Text Available Apresentamos uma revisão sobre trauma renal, com ênfase na avaliação radiológica, particularmente com o uso da tomografia computadorizada, que tem se tornado o exame de eleição, ao invés da urografia excretora e arteriografia. O sucesso no tratamento conservador dos pacientes com trauma renal depende de um acurado estadiamento da extensão da lesão, classificado de acordo com a Organ Injury Scaling do Colégio Americano de Cirurgiões. O tratamento conservador não-operatório é seguro e consiste de observação contínua, repouso no leito, hidratação endovenosa adequada e antibioti- coterapia profilática, evitando-se uma exploração cirúrgica desnecessária e possível perda renal. As indicações para exploração cirúrgica imediata são abdome agudo, rápida queda do hematócrito ou lesões associadas determinadas na avaliação radiológica. Quando indicada, a exploração renal após controle vascular prévio é segura, permitindo cuidadosa inspeção do rim e sua reconstrução com sucesso, reduzindo a probabilidade de nefrectomia.We present a revision of the renal trauma with emphasis in the radiographic evaluation, particularly CT scan that it has largely replaced the excretory urogram and arteriogram in the diagnostic worh-up and management of the patient with renal trauma. The successful management of renal injuries depends upon the accurate assessment of their extent in agreement with Organ Injury Scaling classification. The conservative therapy managed by careful continuous observation, bed rest, appropriate fluid ressuscitation and prophylactic antibiotic coverage after radiographic staging for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss. The indications for immediate exploratory laparotomy were acute abdomen, rapidly dropping hematocrit or associated injuries as determinated from radiologic evaluation. When indicated, renal exploration

  7. Efficacy and safety of low molecular weight heparin compared to unfractionated heparin for chronic outpatient hemodialysis in end stage renal disease: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ghanshyam Palamaner Subash Shantha

    2015-03-01

    Full Text Available Background. Low molecular weight heparin (LMWH is an effective anti-coagulant for thrombotic events. However, due to its predominant renal clearance, there are concerns that it might be associated with increased bleeding in patients with renal disease.Objectives. We systematically evaluated the efficacy and safety of LMWH compared to unfractionated heparin (UH in end stage renal disease (ESRD patients.Search Methods. Pubmed, Embase and cochrane central were searched for eligible citations.Selection Criteria. Randomized controlled trials, comparing LMWH and UH, involving adult (age > 18 years, ESRD patients receiving outpatient, chronic, intermittent hemodialysis were included.Data Collection and Analysis. Two independent reviewers performed independent data abstraction. I2 statistic was used to assess heterogeneity. Random effects model was used for meta-analysis.Results. Nineteen studies were included for systematic review and 4 were included for meta-analysis. There were no significant differences between LMWH and UFH for extracorporeal circuit thrombosis [risk ratio: 1 (95% CI [0.62–1.62

  8. Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients.

    Science.gov (United States)

    McAdoo, Stephen P; Tanna, Anisha; Hrušková, Zdenka; Holm, Lisa; Weiner, Maria; Arulkumaran, Nishkantha; Kang, Amy; Satrapová, Veronika; Levy, Jeremy; Ohlsson, Sophie; Tesar, Vladimir; Segelmark, Mårten; Pusey, Charles D

    2017-09-01

    Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  9. Comparative Study of the Effects of Pyridoxine, Rifampin, and Renal Function on Hematological Adverse Events Induced by Linezolid▿

    OpenAIRE

    2007-01-01

    Hematological disturbances that develop during linezolid treatment are a major concern when linezolid is administered for prolonged periods of time. The aim of this study was to evaluate the influences of pyridoxine, rifampin, and renal function on hematological adverse events. From January 2002 to April 2006, 52 patients received a long-term course of linezolid. Blood cell counts were monitored weekly. Thrombocytopenia was defined as a decrease to

  10. Renal arteriography

    Science.gov (United States)

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Review Date 1/5/2016 Updated by: Jason Levy, ...

  11. Comparative toxicity of mycotoxins to navel orangeworm (Amyelois transitella) and corn earworm (Helicoverpa zea).

    Science.gov (United States)

    Niu, Guodong; Siegel, Joel; Schuler, Mary A; Berenbaum, May R

    2009-08-01

    Mycotoxins, such as aflatoxins and ochratoxins, are widely distributed in nature and are frequently problematic crop contaminants that cause millions of dollars of annual losses in the United States. Insect infestations of crop plants significantly exacerbate mycotoxin contamination. Damage to a variety of nut species by Amyelois transitella Walker (navel orangeworm, NOW) is associated with infection by Aspergillus species and concomitant production of aflatoxins and ochratoxins. Resistance to aflatoxins in this lepidopteran is compared here with the levels of resistance in Helicoverpa zea (corn earworm, CEW), another lepidopteran that routinely encounters aflatoxins in its diet, albeit at lower levels. Measured as the developmental delay caused by aflatoxin B1 (AFB1), it is apparent that the LC(50) (defined as the concentration preventing 50% of newly hatched larvae from entering the 2nd instar within 48 h) for AFB1 is 100 times greater for A. transitella than for H. zea. Similarly, A. transitella 1st instars display substantially higher tolerance to ochratoxin A, another mycotoxin contaminant produced by Aspergillus species, than do H. zea. Our studies indicate that A. transitella, although a hostplant generalist, may well be highly specialized for mycotoxin detoxification.

  12. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Energy Technology Data Exchange (ETDEWEB)

    Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

    2014-09-15

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

  13. A Pooled Analysis Evaluating Renal Safety in Placebo- and Active Comparator-Controlled Phase III Trials of Multiple-Dose Injectable HPβCD-Diclofenac in Subjects with Acute Postoperative Pain.

    Science.gov (United States)

    Daniels, Stephen E; Gan, Tong J Tj; Hamilton, Douglas A; Singla, Neil; Lacouture, Peter G; Johnson, Olufunmibi; Min, Lauren H; Reyes, Christian R D; Carr, Daniel B

    2016-12-01

    OBJECTIVE : While injectable nonsteroidal anti-inflammatory drugs (NSAIDs) are a key component of postoperative multimodal analgesia, renal safety concerns may limit use in some patients. This study examined the renal safety of injectable HPβCD-diclofenac when given for ≤ 5 days following orthopedic or abdominal/pelvic surgery. METHODS : Pooled analysis of data from two randomized, placebo- and active comparator-controlled phase III trials in 608 total patients was conducted. Renal safety was assessed by examining treatment-emergent adverse events (AEs) and postoperative blood urea nitrogen (BUN) and serum creatinine shifts. RESULTS : There were three renal AEs each in the HPβCD-diclofenac (n = 318 patients) and placebo (n = 148 patients) groups, and two renal AEs in the ketorolac group (n = 142 patients). No significant difference in renal AE risk was detected for patients receiving HPβCD-diclofenac (RR: 1.40 [0.15,13.3]; P = 0.75) or ketorolac (RR: 2.08 [0.19,22.7]; P = 0.56) versus placebo. All renal AEs were mild or moderate in severity, and a single renal AE (acute renal failure in a patient receiving HPβCD-diclofenac) was treatment-related. One incidence of postoperative shift to high (> upper limit of normal) serum creatinine occurred in the HPβCD-diclofenac group (n = 2 in the ketorolac group). Mean changes in serum creatinine or BUN did not differ significantly between patients receiving HPβCD-diclofenac and placebo. CONCLUSIONS : While this analysis examined relatively brief exposure typical for parenterally administered analgesics in the postoperative setting in patients with largely normal renal function, the results suggest that HPβCD-diclofenac use for acute postoperative pain may not be associated with added renal safety risks over placebo in this patient population.

  14. Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

    Directory of Open Access Journals (Sweden)

    Bridget M. Stroup

    2017-01-01

    Full Text Available Background. Skeletal fragility is a complication of phenylketonuria (PKU. A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF. Design. In a crossover design, 8 participants with PKU (16–35 y provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL of AA-MF and GMP-MF and determined bone mineral density (BMD measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p=0.002. Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p=0.012 and magnesium by 30% (p=0.029. Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258.

  15. Comparative acute toxicity of leachates from plastic products made of polypropylene, polyethylene, PVC, acrylonitrile-butadiene-styrene, and epoxy to Daphnia magna.

    Science.gov (United States)

    Lithner, Delilah; Nordensvan, Ildikó; Dave, Göran

    2012-06-01

    The large global production of plastics and their presence everywhere in the society and the environment create a need for assessing chemical hazards and risks associated with plastic products. The aims of this study were to determine and compare the toxicity of leachates from plastic products made of five plastics types and to identify the class of compounds that is causing the toxicity. Selected plastic types were those with the largest global annual production, that is, polypropylene, polyethylene, and polyvinyl chloride (PVC), or those composed of hazardous monomers (e.g., PVC, acrylonitrile-butadiene-styrene [ABS], and epoxy). Altogether 26 plastic products were leached in deionized water (3 days at 50°C), and the water phases were tested for acute toxicity to Daphnia magna. Initial Toxicity Identification Evaluations (C18 filtration and EDTA addition) were performed on six leachates. For eleven leachates (42%) 48-h EC50s (i.e the concentration that causes effect in 50 percent of the test organisms) were below the highest test concentration, 250 g plastic/L. All leachates from plasticized PVC (5/5) and epoxy (5/5) products were toxic (48-h EC50s ranging from 2 to 235 g plastic/L). None of the leachates from polypropylene (5/5), ABS (5/5), and rigid PVC (1/1) products showed toxicity, but one of the five tested HDPE leachates was toxic (48-h EC50 17-24 g plastic/L). Toxicity Identification Evaluations indicated that mainly hydrophobic organics were causing the toxicity and that metals were the main cause for one leachate (metal release was also confirmed by chemical analysis). Toxic chemicals leached even during the short-term leaching in water, mainly from plasticized PVC and epoxy products.

  16. A Human Renal Proximal Tubule Cell Line with Stable Organic Anion Transporter 1 and 3 Expression Predictive for Antiviral-Induced Toxicity

    NARCIS (Netherlands)

    Nieskens, Tom T G; Peters, Janny G P; Schreurs, Marieke J; Smits, Niels; Woestenenk, Rob; Jansen, Katja; van der Made, Thom K; Röring, Melanie; Hilgendorf, Constanze; Wilmer, Martijn J; Masereeuw, Roos

    2016-01-01

    Drug-induced nephrotoxicity still hampers drug development, because current translation from in vitro or animal studies to human lacks high predictivity. Often, renal adverse effects are recognized only during clinical stages of drug development. The current study aimed to establish a robust and a m

  17. Early detection of femoral head avascular necrosis by bone SPECT compared to MRI in renal allograft recipients

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young; Yang, Seoung Oh; Lee, Hee Kyung; Han, Duck Jong; Shin, Myung Jin [Asan Mecical Center, Seoul (Korea, Republic of)

    1997-07-01

    The prevalence of avascular necrosis (AVN) of femoral head in patients who receive immunosuppresive agents after renal transplantation is reported to be 4-29%. Among patients who develop AVN after renal transplantation, 80% become symptomatic within 2 years after transplantation. As the number of renal transplantation has been increased recently, early detection of femoral head AVN is very important because early surgical core decompression of femoral head can prevent collapse of the head. MRI is known to be very sensitive to diagnose femoral head AVN. However in three cases we report here, bone SPECT showed early changes of femoral head AVN, whereas MRI showed no specific abnormality. Case 1. A 53-year-old female received an allograft kidney transplantation in 1994. Preoperative bone scan was normal. She complained of both hip pain on Mar. 18 1997. Bone SPECT showed cold defect in both femoral heads but MRI showed no abnormality. After 3 months, bone SPECT and MRI showed AVN of both femoral heads. She underwent bilateral total hip replacement arthroplasty. AVN of femoral heads was confirmed by microscopic examination. Case 2. A 38-year-old female received an allograft kidney transplantation in Feb. 27 1997. Preoperative bone scan was normal. She ran a fever and creatinine was elevated from 1.2 to 2.8 mg/dL. She took high dose methylprednisolone therapy for acute reanl rejection. After two days, she complained pain in both hip joints and knee joints. Bone SPECT showed cold defects in both femoral heads but MRI showed no abnormality. A follow-up bone SPECT and MRI 20 days later revealed AVN of both femoral heads. Case 3. A 50-year-old male received an allograft kidney transplantation on Jul. 12 1995. Preoperative bone scan was normal. He complained of right hip pain on Jul, 26 1995. His bone SPECT showed cold defects in both femoral heads while MRI showed only minimal hip joint effusion. He also complained of left hip pain on Oct. 2 1995. He was admitted on Mar 17

  18. Effectiveness of pharmacist dosing adjustment for critically ill patients receiving continuous renal replacement therapy: a comparative study

    OpenAIRE

    Jiang SP; Zhu ZY; Wu XL; Lu XY; Zhang XG; Wu BH

    2014-01-01

    Sai-Ping Jiang,1 Zheng-Yi Zhu,2 Xiao-Liang Wu,3 Xiao-Yang Lu,1 Xing-Guo Zhang,1 Bao-Hua Wu1 1Department of Pharmacy, the First Affiliated Hospital, 2Department of Pharmacy, Children’s Hospital, College of Medicine, Zhejiang University, Hangzhou, 3Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China Background: The impact of continuous renal replacement therapy (CRRT) on drug removal is complicated...

  19. A randomized trial comparing renal function in older kidney transplant patients following delayed versus immediate tacrolimus administration.

    Science.gov (United States)

    Andrés, Amado; Budde, Klemens; Clavien, Pierre-Alain; Becker, Thomas; Kessler, Michèle; Pisarski, Przemyslaw; Fornara, Paolo; Burmeister, Dirk; Hené, Ronald J; Cassuto-Viguier, Elisabeth

    2009-11-15

    This large, randomized, multicenter trial evaluated if basiliximab induction and delayed tacrolimus can preserve renal function in older kidney transplant patients. Patients aged 60 years and older received delayed tacrolimus with basiliximab and mycophenolate mofetil with early steroid discontinuation (Tac-d, n=132) or standard tacrolimus with mycophenolate mofetil and steroids until day 91 (Tac-s, n=122). Tacrolimus trough levels were 5 to 10 ng/mL after day 43 in both groups. Renal function at month 6 was measured by calculated creatinine clearance (Cockcroft-Gault formula). In both groups, mean recipient age was 66 years, mean donor age was 63 years with 73% of donors aged 60 years and older. Steroid discontinuation was slower than protocol specified. In the Tac-d group, 56.1% were steroid free at day 14 and 81.8% at month 6. In the Tac-s group, 37.7% were steroid free at month 4 and 63.9% at month 6. Mean (+/-SD) calculated creatinine clearance was 45.7+/-16.1 mL/min (Tac-d) and 45.0+/-18.2 mL/min (Tac-s) (P=ns), mean glomerular filtration rate (modified diet in renal disease formula) was 44.9+/-16.2 mL/min and 41.6+/-16.8 mL/min, respectively. Incidences of biopsy-proven acute rejection were 18.9% (Tac-d) and 18.0% (Tac-s). Delayed graft function was 30.3% (Tac-d) and 23.8% (Tac-s). Estimated patient survival rates (Kaplan-Meier) in the Tac-d and Tac-s groups were 96.1% vs. 99.2% and estimated graft survival rates were 90% vs. 87.6%, respectively. Safety results were similar with both regimens. Delayed tacrolimus with basiliximab induction did not provide an advantage in preserving renal function or reducing delayed graft function in older kidney transplant patients.

  20. A simultaneous multiple species acute toxicity test comparing relative sensitivities of six aquatic organisms to HgCl{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    McCrary, J.E.; Heagler, M.G. [McNeese State Univ., Lake Charles, LA (United States). Dept. of Biological and Environmental Science

    1995-12-31

    In the last few years there has been concern in the scientific community about observed declines in some amphibian species. These population declines could be reflecting a global phenomenon due to a general class sensitivity or may be part of a natural cycle. The suggestion of an overall greater sensitivity of amphibians is not supported. Studies show that amphibians, as a class, are neither more or less susceptible than fish to environmental conditions. Mercury has been found to be one of the most toxic of the heavy metals introduced into amphibian breeding waters. Six aquatic species were simultaneously exposed in a comparative acute toxicity test with mercury chloride: three amphibians, Rana catesbeiana (bullfrog), R. clamitans (green frog), and R. sphenocephala (southern leopard frog, formally classified as R. utricularia); two fish, Gambusia affinis (mosquitofish) and Notemigonus crysoleucas (golden shiner); one aquatic aligochaete, Lumbriculus variegatus (aquatic earthworm). The five test concentrations used were 1.4, 3.9, 12.0, 110.0, and 487.0 {micro}g Hg/L respectively. Ten organisms per species were randomly placed into the six test tanks (control and five concentrations), each species in a separate chamber. The resultant LC50-96hr values produced the following rank order: R. sphenocephala, 6.59 {micro}g Hg/L; R. clamitans, 14.7 {micro}g Hg/L; N. crysoleucas, 16.75 {micro}g Hg/L; L. variegatus, 43.72,ug Hg/L; G. affinis, 52.62 {micro}g Hg/L; R. catesbeiana, 63.36 {micro}g Hg/L. No general organism class sensitivity trend, for amphibians, was developed from this data, contrary to the implicit suggestions of some researchers.

  1. A comparative analysis on the in vivo toxicity of copper nanoparticles in three species of freshwater fish.

    Science.gov (United States)

    Song, Lan; Vijver, Martina G; Peijnenburg, Willie J G M; Galloway, Tamara S; Tyler, Charles R

    2015-11-01

    Copper nanoparticles (CuNPs) are used extensively in a wide range of products and the potential for toxicological impacts in the aquatic environment is of high concern. In this study, the fate and the acute toxicity of spherical 50nm copper nanoparticles was assessed in juvenile rainbow trout (Oncorhynchus mykiss), fathead minnow (Pimephales promelas) and zebrafish (Danio rerio) for in vivo aqueous exposures following standardized OECD 203 guideline tests. The fate of the CuNPs in the aqueous media was temperature dependent. At the higher study temperature (26±1°C), there was both an enhanced particle aggregation and higher rate of dissolution compared with that at the lower study temperature (15±1°C). 96h LC50s of the CuNPs were 0.68±0.15, 0.28±0.04 and 0.22±0.08mg Cu/L for rainbow trout, fathead minnow and zebrafish, respectively. The 96h lowest-observed-effect concentration (LOEC) for the CuNPs were 0.17, 0.023 and copper was one of main drivers for the acute toxicity of the copper nanoparticles suspensions. Both CuNPs suspension and copper nitrate caused damage to gill filaments and gill pavement cells, with differences in sensitivity for these effects between the fish species studied. We show therefore common toxicological effects of CuNPs in different fish species but with differences in sensitivity with implications for hazard extrapolation between fish species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Comparing the effectiveness of chronic water column tests with the crustaceans Hyalella azteca (order: Amphipoda) and Ceriodaphnia dubia (order: Cladocera) in detecting toxicity of current-use insecticides.

    Science.gov (United States)

    Deanovic, Linda A; Markiewicz, Dan; Stillway, Marie; Fong, Stephanie; Werner, Inge

    2013-03-01

    Standard U.S. Environmental Protection Agency laboratory tests are used to monitor water column toxicity in U.S. surface waters. The water flea Ceriodaphnia dubia is among the most sensitive test species for detecting insecticide toxicity in freshwater environments.Its usefulness is limited, however, when water conductivity exceeds 2,000 µS/cm (approximately 1 ppt salinity) and test effectiveness is insufficient. Water column toxicity tests using the euryhaline amphipod Hyalella azteca could complement C. dubia tests; however, standard chronic protocols do not exist. The present study compares the effectiveness of two water column toxicity tests in detecting the toxicity of two organophosphate (OP) and two pyrethroid insecticides: the short-term chronic C. dubia test, which measures mortality and fecundity, and a 10-d H. azteca test, which measures mortality and growth. Sensitivity was evaluated by comparing effect data, and end point variability was evaluated by comparing minimum significant differences. Tests were performed in synthetic water and filtered ambient water to quantify the influence of water matrix on effect concentrations. The H. azteca test detected pyrethroid toxicity far more effectively, while the C. dubia test was more sensitive to OPs. Among endpoints, H. azteca mortality was most robust. The results demonstrate that the H. azteca test is preferable when conductivity of water samples is 2,000 to 10,000 µS/cm or if contaminants of concern include pyrethroid insecticides.

  3. Incidental renal neoplasms

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen;

    2014-01-01

    On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

  4. Relative developmental toxicity potencies of retinoids in the embryonic stem cell test compared with their relative potencies in in vivo and two other in vitro assays for developmental toxicity

    NARCIS (Netherlands)

    Louisse, J.; Gönen, S.; Rietjens, I.M.C.M.; Verwei, M.

    2011-01-01

    The present study determines the relative developmental toxicity potencies of retinoids in the embryonic stem (ES)-D3 cell differentiation assay of the embryonic stem cell test, and compares the outcomes with their relative potencies in in vivo and two other in vitro assays for developmental toxicit

  5. Relationship between cisplatin or nedaplatin-induced nephrotoxicity and renal accumulation.

    Science.gov (United States)

    Kawai, Yoshiko; Taniuchi, Saburo; Okahara, Shigeki; Nakamura, Masuhisa; Gemba, Munekazu

    2005-08-01

    Nedaplatin is known to exhibit antitumor activity similar to that of cisplatin. However, concerning side effects, nedaplatin causes renal toxicity less frequently than cisplatin. In this study, we compared the incidence of renal toxicity between cisplatin and nedaplatin by investigating the difference in kidney tissue accumulation. Kidney tissue accumulation of cisplatin administered at 3.75 mg/kg was similar to that of nedaplatin administered at 24 mg/kg. At these doses, the plasma creatinine level and urinary excretion of glucose and N-acetyl-beta-D-glucosaminidase (NAG) similarly increased. There was a correlation between kidney accumulation of cisplatin and nedaplatin and the increases in plasma creatinine level and urinary excretion of NAG. Therefore, our results suggest that nedaplatin less frequently causes renal toxicity in comparison to cisplatin due to lower kidney accumulation.

  6. Soil pH effects on the comparative toxicity of dissolved zinc, non-nano and nano ZnO to the earthworm Eisenia fetida.

    Science.gov (United States)

    Heggelund, Laura R; Diez-Ortiz, Maria; Lofts, Stephen; Lahive, Elma; Jurkschat, Kerstin; Wojnarowicz, Jacek; Cedergreen, Nina; Spurgeon, David; Svendsen, Claus

    2014-08-01

    To determine how soil properties influence nanoparticle (NP) fate, bioavailability and toxicity, this study compared the toxicity of nano zinc oxide (ZnO NPs), non-nano ZnO and ionic ZnCl2 to the earthworm Eisenia fetida in a natural soil at three pH levels. NP characterisation indicated that reaction with the soil media greatly controls ZnO properties. Three main conclusions were drawn. First that Zn toxicity, especially for reproduction, was influenced by pH for all Zn forms. This can be linked to the influence of pH on Zn dissolution. Secondly, that ZnO fate, toxicity and bioaccumulation were similar (including relationships with pH) for both ZnO forms, indicating the absence of NP-specific effects. Finally, earthworm Zn concentrations were higher in worms exposed to ZnO compared to ZnCl2, despite the greater toxicity of the ionic form. This observation suggests the importance of considering the relationship between uptake and toxicity in nanotoxicology studies.

  7. [Semi-invasive monitoring of cardiac output in renal transplantation by a new device using arterial pressure waveform analysis compare with intermittent pulmonary thermodilution].

    Science.gov (United States)

    Terada, Takashi; Maemura, Yumi; Toyoda, Daisuke; Iwasaki, Ririko; Sato, Nobukazu; Ochtai, Ryoichi

    2010-07-01

    Clinical usefulness of PA catheter is controversial. We compared a new semi-invasive device (FloTrac/Vigileo) using arterial pressure waveform analysis for CO measurement in patients undergoing renal transplantation with bolus thermodilution method. Simultaneously CCO was measured, and we compared CCO with that obtained by bolus thermodilution method. Forty seven patients undergoing renal transplantation were enrolled. A PAC was inserted and radial arterial access was used for semi-invasive determination of CO (APCO) with the Vigileo. CO was measured simultaneously by bolus thermodilution and the Vigileo technique, and after starting operation, volume loading, before surgery, and other points were measured over 1 hour during measurements. And CCO was measured simultaneously at all points. Statistical analysis was performed using the method described by Bland and Altman. Bias was defined as the mean difference between the volumes obtained by pulmonary artery thermodilution and those by arterial pressure waveform analysis. Precision was expressed by the upper and lower limits of agreement. Means of age, height and weight were 45 years, 163.8 cm and 59.2 kg, respectively. Regression analysis of CO; APCO and ICO showed y = 0.8x + 2.2, R2 = 0.57. CCO and ICO; y = 0.8x + 1.1, R2 = 0.74. Average of APCO and ICO; bias = -0.65. SD = 1.54 average of CCO and ICO; bias = 0.38, SD = 1.23. In renal transplantation, CO measured by a new semi-invasive arterial pressure waveform analysis device showed good agreement with the volume obtained by intermittent pulmonary artery thermodilution method.

  8. Angiography for renal artery stenosis: no additional impairment of renal function by angioplasty

    Energy Technology Data Exchange (ETDEWEB)

    Lufft, Volkmar; Fels, Lueder M.; Egbeyong-Baiyee, Daniel; Olbricht, Christoph J. [Abteilung Nephrologie, Medizinische Hochschule Hannover (Germany); Hoogestraat-Lufft, Linda; Galanski, Michael [Abteilung Diagnostische Radiologie, Medizinische Hochschule Hannover (Germany)

    2002-04-01

    The aim of this study was to compare renal function between patients with renal angiography and patients with renal angiography and angioplasty (AP) for renal artery stenosis (RAS). Forty-seven patients with suspected RAS were prospectively investigated by digital subtraction angiography (DSA) using non-ionic low osmolar contrast media (CM). In 22 patients RAS was detected and in 16 cases an angioplasty was performed in the same session. The following parameters were determined 1 day prior to and after the DSA, respectively: serum creatinine (S-Crea, {mu}mol/l) and single-shot inulin clearance (In-Cl, ml/min) for the evaluation of renal function; and urine alpha 1-microglobuline (AMG, {mu}g/g Crea) and beta-N-acetyl-glucoseaminidase (beta-NAG, U/g Crea) as markers of tubular toxicity. Serum creatinine was measured additionally 2 days after CM had been injected. In both groups with and without AP 174{+-}65 and 104{+-}56 ml of CM (p<0.0005) were used, respectively. There were no differences with regard to renal function or risk factors for CM nephrotoxicity between both groups. In the group with AP S-Crea and In-Cl (each: mean{+-}SD) did not change significantly (before DSA: 171{+-}158 and 61{+-}24, after DSA: 189{+-}177 and 61{+-}25, respectively), beta-NAG (median) rose from 4 to 14 (p<0.05) and AMG from 8 to 55 (n.s., because of high SD). In the group without AP S-Crea increased from 134{+-}109 to 141{+-}113 (p<0.01), In-Cl dropped from 65{+-}26 to 62{+-}26 (p<0,01), beta NAG (median) rose from 4 to 8 (p=0.01), and AMG from 7 to 10 (n.s.). A rise in baseline S-Crea by more than 25% or 44 {mu}mol/l occurred in 4 and 2 patients in the group with and without AP, respectively. Creatinine increase was reversible in all cases within 7 days. In this study using sensitive methods to detect changes of renal function and tubular toxicity no additional renal function impairment in DSA with angioplasty for RAS compared with DSA alone could be demonstrated. Our data suggest

  9. Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells.

    Science.gov (United States)

    Khan, Mohammed I; Czarnecka, Anna M; Lewicki, Sławomir; Helbrecht, Igor; Brodaczewska, Klaudia; Koch, Irena; Zdanowski, Robert; Król, Magdalena; Szczylik, Cezary

    2016-01-01

    Recent advancement in cancer research has shown that tumors are highly heterogeneous, and multiple phenotypically different cell populations are found in a single tumor. Cancer development and tumor growth are driven by specific types of cells-stem cell-like cancer cells (SCLCCs)-which are also responsible for metastatic spread and drug resistance. This research was designed to verify the presence of SCLCCs in renal cell cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumor-initiating cells. The main goal of the project was to describe the gene-expression profile of stem cell-like cancer cells of primary tumor and metastatic origin. Real-time PCR analysis of stemness genes (Oct-4, Nanog and Ncam) and soft agar colony formation assay were conducted to check the stemness properties of renal cell carcinoma (RCC) cell lines. FACS analysis of CD105+ and CD133+ cells was performed on RCC cells. Isolated CD105+ cells were verified for expression of mesenchymal markers-CD24, CD146, CD90, CD73, CD44, CD11b, CD19, CD34, CD45, HLA-DR and alkaline phosphatase. Hanging drop assay was used to investigate CD105+ cell-cell cohesion. Analysis of free-floating 3D spheres formed by isolated CD105+ was verified, as spheres have been hypothesized to contain undifferentiated multipotent progenitor cells. Finally, CD105+ cells were sorted from primary (Caki-2) and metastatic (ACHN) renal cell cancer cell lines. Gene-expression profiling of sorted CD105+ cells was performed with Agilent's human GE 4x44K v2 microarrays. Differentially expressed genes were further categorized into canonical pathways. Network analysis and downstream analysis were performed with Ingenuity Pathway Analysis. Metastatic RCC cell lines (ACHN and Caki-1) demonstrated higher colony-forming ability in comparison to primary RCC cell lines. Metastatic RCC cell lines harbor numerous CD105+ cell subpopulations and have

  10. Five-year results of a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation: the SPIESSER study.

    Science.gov (United States)

    Lebranchu, Y; Snanoudj, R; Toupance, O; Weestel, P-F; Hurault de Ligny, B; Buchler, M; Rerolle, J-P; Thierry, A; Moulin, B; Subra, J-F; Deteix, P; Le Pogamp, P; Finzi, L; Etienne, I

    2012-07-01

    Calcineurin inhibitors improve acute rejection rates and short-term graft survival in renal transplantation, but their continuous use may be deleterious. We evaluated the 5-year outcomes of sirolimus (SRL) versus cyclosporine (CsA) immunosuppressive treatment. This observational study was an extension of the SPIESSER study where deceased donor kidney transplant recipients were randomized before transplantation to a SRL- or CsA-based regimen and followed up 1 year. Data from 131 (63 SRL, 68 CsA) out of 133 patients living with a functional graft at 1 year were collected retrospectively at 5 years posttransplant. Seventy percent of CsA patients versus 54% of SRL patients were still on the allocated treatment at 5 years (p = 0.091), most discontinuations in each group being due to safety issues. In intent-to-treat, mean MDRD eGFR was higher with SRL: 54.2 versus 45.3 mL/min with CsA (p = 0.019); SRL advantage was greater in on-treatment analyses. There were no differences for patient survival (p = 0.873), graft survival (p = 0.121) and acute rejection (p = 0.284). Adverse events were more frequent with SRL (80% vs. 60%, p = 0.015). Results confirmed the high SRL discontinuation rate due to adverse events. Nevertheless, a benefit was evidenced on renal function in patients (more than 50%) still on treatment at 5 years. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  11. Bioaugmentation and biostimulation as strategies for the bioremediation of a burned woodland soil contaminated by toxic hydrocarbons: a comparative study.

    Science.gov (United States)

    Andreolli, Marco; Lampis, Silvia; Brignoli, Pierlorenzo; Vallini, Giovanni

    2015-04-15

    In this work, the natural attenuation strategy (no soil amendments done) was compared with two different bioremediation approaches, namely bioaugmentation through soil inoculation with a suspension of Trichoderma sp. mycelium and biostimulation by soil addition with a microbial growth promoting formulation, in order to verify the effectiveness of these methods in terms of degradation efficiency towards toxic hydrocarbons, with particular attention to the high molecular weight (HMW) fraction, in a forest area impacted by recent wildfire in Northern Italy. The area under investigation, divided into three parcels, was monitored to figure out the dynamics of decay in soil concentration of C₁₂₋₄₀ hydrocarbons (including isoalkanes, cycloalkanes, alkyl-benzenes and alkyl-naphthalenes besides PAHs) and low molecular weight (LMW) PAHs, following the adoption of the foregoing different remediation strategies. Soil hydrocarbonoclastic potential was even checked by characterizing the autochthonous microbial cenoses. Field experiments proved that the best performance in the abatement of HMW hydrocarbons was reached 60 days after soil treatment through the biostimulation protocol, when about 70% of the initial concentration of HMW hydrocarbons was depleted. Within the same time, about 55% degradation was obtained with the bioaugmentation protocol, whilst natural attenuation allowed only a 45% removal of the starting C12-40 hydrocarbon fraction. Therefore, biostimulation seems to significantly reduce the time required for the remediation, most likely because of the enhancement of microbial degradation through the improvement of nutrient balance in the burned soil.

  12. A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional external-beam radiotherapy for localized prostate adenocarcinoma. A report on acute toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Norkus, Darius; Miller, Albert; Kurtinaitis, Juozas; Valuckas, Konstantinas Povilas [Dept. of Radiotherapy, Inst. of Oncology, Vilnius Univ. (Lithuania); Haverkamp, Uwe [Dept. of Radiology, Clemenshospital, Muenster (Germany); Popov, Sergey [Dept. of Radiotherapy, Riga Eastern Hospital, Latvian Oncology Center, Riga (Latvia); Prott, Franz-Josef [Inst. of Radiology and Radiotherapy (RNS), St. Josefs Hospital, Wiesbaden (Germany)

    2009-11-15

    Purpose: to compare acute gastrointestinal (GI) and genitourinary (GU) toxicity between patient groups with localized prostate adenocarcinoma, treated with conventionally fractionated (CFRT) and hypofractionated (HFRT) three-dimensional conformal external-beam radiotherapy (3D-CRT). Patients and methods: 91 patients were enrolled into a randomized study with a minimum follow-up of 3 months. 44 men in the CFRT arm were irradiated with 74 Gy in 37 fractions at 2 Gy per fraction for 7.5 weeks. 47 men in the HFRT arm were treated with 57 Gy in 17 fractions for 3.5 weeks, given as 13 fractions of 3 Gy plus four fractions of 4.5 Gy. The clinical target volume (CTV) included the prostate and the base of seminal vesicles. The CTV-to-PTV (planning target volume) margin was 8-10 mm. Study patients had portal imaging and/or simulation performed on the first fractions and repeated at least weekly. Results: no acute grade 3 or 4 toxicities were observed. The grade 2 GU acute toxicity proportion was significantly lower in the HFRT arm: 19.1% versus 47.7% ({chi}{sup 2}-test, p = 0.003). The grade 2 GU acute toxicity-free survival was significantly better in the HFRT arm (log-rank test, p = 0.008). The median duration of overall GI acute toxicity was shorter with HFRT: 3 compared to 6 weeks with CFRT (median test, p = 0.017). Conclusion: in this first evaluation, the HFRT schedule is feasible and induces acceptable or even lower acute toxicity compared with the toxicities in the CFRT schedule. Extended follow-up is needed to justify this fractionation schedule's safety in the long term. (orig.)

  13. Comparative short-term inhalation toxicity of five organic diketopyrrolopyrrole pigments and two inorganic iron-oxide-based pigments

    Science.gov (United States)

    Hofmann, Thomas; Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Rey Moreno, Maria; Neubauer, Nicole; Wohlleben, Wendel; Gröters, Sibylle; Wiench, Karin; Veith, Ulrich; Teubner, Wera; van Ravenzwaay, Bennard; Landsiedel, Robert

    2016-01-01

    Abstract Diketopyrrolopyrroles (DPP) are a relatively new class of organic high-performance pigments. The present inhalation and particle characterization studies were performed to compare the effects of five DPP-based pigments (coarse and fine Pigment Red 254, coarse and fine meta-chloro DPP isomer and one form of mixed chlorinated DPP isomers) and compare it to coarse and fine inorganic Pigment Red 101. Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 h/day on 5 consecutive days. Target concentrations were 30 mg/m3 as high dose for all compounds and selected based occupational exposure limits for respirable nuisance dust. Toxicity was determined after end of exposure and after 3-week recovery using broncho-alveolar lavage fluid (BALF) and microscopic examinations of the entire respiratory tract. Mixed chlorinated DPP isomers and coarse meta-chloro DPP isomer caused marginal changes in BALF, consisting of slight increases of polymorphonuclear neutrophils, and in case of coarse meta-chloro DPP increased MCP-1 and osteopontin levels. Mixed chlorinated DPP isomers, Pigment Red 254, and meta-chloro DPP caused pigment deposits and phagocytosis by alveolar macrophages, slight hypertrophy/hyperplasia of the bronchioles and alveolar ducts, but without evidence of inflammation. In contrast, only pigment deposition and pigment phagocytosis were observed after exposure to Pigment Red 101. All pigments were tolerated well and caused only marginal effects in BALF or no effects at all. Only minor effects were seen on the lung by microscopic examination. There was no evidence of systemic inflammation based on acute-phase protein levels in blood. PMID:27387137

  14. A multi-center, comparative, phase 3 study to determine the efficacy of gadofosveset-enhanced magnetic resonance angiography for evaluation of renal artery disease

    Energy Technology Data Exchange (ETDEWEB)

    McGregor, Robert [St. Boniface General Hospital, Winnipeg, Manitoba (Canada); Vymazal, Josef [Hospital Na Homolce, Prague (Czech Republic); Martinez-Lopez, Manuel [Hospital Medica Sur, Mexico City (Mexico); Neuwirth, Jiri [Faculty Hospital Motol, Prague (Czech Republic); Salgado, Perla [American British Cowdray Medical Center, Mexico City (Mexico); Beregi, Jean-Paul [Hopital Cardiologique, Lille (France); Peduto, Anthony [Westmead Hospital, Westmead New South Wales (Australia); Pena-Almaguer, Erasmo de la [Christus-Muguerza Medical Center, Monterrey, Nuevo Leon (Mexico); Slater, Greg J. [Greenslopes Private Hospital, Greenslopes, Queensland (Australia); Shamsi, Kohkan [Berlex Laboratories, Montville, NJ (United States); Parsons, Edward C. [EPIX Pharmaceuticals, Inc., Lexington, MA (United States)], E-mail: eparsons@epixpharma.com

    2008-02-15

    Purpose: To determine prospectively the safety and efficacy of the blood-pool contrast agent gadofosveset trisodium in renal artery magnetic resonance angiography (MRA). Materials and methods: Gadofosveset (0.03 mmol/kg) was administered to adult patients with known or suspected renal arterial disease in a multi-center phase 3 single dose study. The drug binds reversibly to albumin, prolonging the blood residence time, and allowing collection of images in the first-pass and steady-state phases. The combination of these images was compared to non-contrast MRA, using catheter X-ray angiography (XRA) as the standard of reference (SOR). All MRA images were collected at 1.5 T in one imaging session for direct comparison, and XRA within 30 days. Sensitivity, specificity, and accuracy for diagnosing significant disease (stenosis {>=}50%) were calculated for MRA using three independent blinded readers. Patient safety was monitored for 72-96 h. Results: A total of 145 patients at 18 centers were enrolled and received gadofosveset; the 127 with complete efficacy data entered the primary efficacy analysis. Gadofosveset-enhanced MRA led to significant improvement (p < 0.01) in sensitivity (+25%, +26%, +42%), specificity (+23%, +25%, +29%), and accuracy (+23%, +28%, +29%) over non-enhanced MRA for the three readers. The rate of uninterpretable examinations decreased from 30% to less than 2%. There were no serious adverse events, and the most common adverse events were nausea, pruritis, and headache (8% each). No significant trends in clinical chemistry parameters, nor significant changes in serum creatinine, were found following administration of gadofosveset. Conclusion: In patients with known or suspected renal arterial disease, multi-phase gadofosveset-enhanced MRA significantly improves sensitivity, specificity, and accuracy versus non-enhanced MRA. Gadofosveset was safe and well tolerated in this patient population.

  15. Comparative Toxicities and Pharmacokinetics of Intrathecal Lipid (Amphotericin B Colloidal Dispersion) and Conventional Deoxycholate Formulations of Amphotericin B in Rabbits

    OpenAIRE

    Clemons, Karl V.; Sobel, Raymond A.; Williams, Paul L.; Stevens, David A.

    2001-01-01

    The lipid formulation of amphotericin B, Amphotec (ABCD), has not been used intrathecally. After a single intrathecal dose or after four doses, conventionally formulated deoxycholate amphotericin B (AMB) (Fungizone) resulted in higher levels of amphotericin B in the cerebrospinal fluid of rabbits than did ABCD. Clinically and histologically, ABCD was about threefold less toxic than AMB after a single dose and 3- to 30-fold less toxic after multiple dosing. These data are encouraging for the p...

  16. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  17. Comparative evaluation of impact of Zn and ZnO nanoparticles on brine shrimp (Artemia salina) larvae: effects of particle size and solubility on toxicity.

    Science.gov (United States)

    Ates, Mehmet; Daniels, James; Arslan, Zikri; Farah, Ibrahim O; Rivera, Hilsamar Félix

    2013-01-01

    Brine shrimp (Artemia salina) larvae were exposed to different sizes of zinc (Zn) and zinc oxide (ZnO) nanoparticles (NPs) to evaluate their toxicity in marine aquatic ecosystems. Acute exposure was conducted in seawater with 10, 50 and 100 mg L(-1) concentrations of the NPs for 24 h and 96 h. Phase contrast microscope images confirmed the accumulation of the NPs inside the guts. Artemia were unable to eliminate the ingested particles, which was thought to be due to the formation of massive particles in the guts. Although the suspensions of the NPs did not exhibit any significant acute toxicity within 24 h, mortalities increased remarkably in 96 h and escalated with increasing concentration of NP suspension to 42% for Zn NPs (40-60 nm) (LC50∼ 100 mg L(-1)) and to about 34% for ZnO NPs (10-30 nm) (LC50 > 100 mg L(-1)). The suspensions of Zn NPs were more toxic to Artemia than those of ZnO NPs under comparable regimes. This effect was attributed to higher Zn(2+) levels (ca. up to 8.9 mg L(-1)) released to the medium from Zn NPs in comparison to that measured in the suspensions of ZnO NPs (ca. 5.5 mg L(-1)). In addition, the size of the nanopowders appeared to contribute to the observed toxicities. Although the suspensions possessed aggregates of comparable sizes, smaller Zn NPs (40-60 nm) were relatively more toxic than larger Zn NPs (80-100 nm). Likewise, the suspensions of 10-30 nm ZnO NPs caused higher toxicity than those of 200 nm ZnO NPs. Lipid peroxidation levels were substantially higher in 96 h (p < 0.05), indicating that the toxic effects were due to the oxidative stress.

  18. Aspects of aluminum toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Hewitt, C.D.; Savory, J.; Wills, M.R. (Univ. of Virginia Health Sciences Center, Charlottesville (USA))

    1990-06-01

    Aluminum is the most abundant metal in the earth's crust. The widespread occurrence of aluminum, both in the environment and in foodstuffs, makes it virtually impossible for man to avoid exposure to this metal ion. Attention was first drawn to the potential role of aluminum as a toxic metal over 50 years ago, but was dismissed as a toxic agent as recently as 15 years ago. The accumulation of aluminum, in some patients with chronic renal failure, is associated with the development of toxic phenomena; dialysis encephalopathy, osteomalacic dialysis osteodystrophy, and an anemia. Aluminum accumulation also occurs in patients who are not on dialysis, predominantly infants and children with immature or impaired renal function. Aluminum has also been implicated as a toxic agent in the etiology of Alzheimer's disease, Guamiam amyotrophic lateral sclerosis, and parkinsonism-dementia. 119 references.

  19. Cost-effectiveness of sorafenib compared to best supportive care in second line renal cell cancer from a payer perspective in Cyprus.

    Science.gov (United States)

    Petrou, Panagiotis Ke; Talias, Michael A

    2014-02-01

    The objective of this study is to assess the cost effectiveness of sorafenib as a second line treatment of advanced renal cell carcinoma compared to standard best supportive care (BSC) in Cyprus. A probabilistic Decision analytic Markov Model was created to simulate disease progression and data from landmark trials were used. Actual local costs were set according to current guidelines in Cyprus. The incremental cost per quality adjusted life year of sorafenib versus BSC was €102,059. The probability of sorafenib to be cost effective at the threshold of €60,000 was 0%. Total costs were sensitive to the price of product, its effectiveness and to a lesser degree to the utility values. Sorafenib demonstrated superior clinical effectiveness compared to BSC, but it's not cost effective under current willingness to pay threshold. Its orphan status along with solidarity principle may justify reimbursement on an individual patient basis.

  20. Targeting of doxorubicin to the urinary bladder of the rat shows increased cytotoxicity in the bladder urine combined with an absence of renal toxicity

    NARCIS (Netherlands)

    Haas, M; Moolenaar, F; Elsinga, A; Van der Wouden, EA; De Jong, PE; Meijer, DKF; De Zeeuw, D

    Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder carcinoma may be useful, since these agents generally have a low degree of urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug doxorubicin was coupled to the low-molecular weight protein

  1. Targeting of doxorubicin to the urinary bladder of the rat shows increased cytotoxicity in the bladder urine combined with an absence of renal toxicity

    NARCIS (Netherlands)

    Haas, M; Moolenaar, F; Elsinga, A; Van der Wouden, EA; De Jong, PE; Meijer, DKF; De Zeeuw, D

    2002-01-01

    Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder carcinoma may be useful, since these agents generally have a low degree of urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug doxorubicin was coupled to the low-molecular weight protein l

  2. Safety and Efficacy of Thermal Ablation for Small Renal Masses in Solitary Kidney: Evidence from Meta-Analysis of Comparative Studies.

    Directory of Open Access Journals (Sweden)

    Quancheng Yang

    Full Text Available To evaluate comparative renal functional preservation, perioperative and oncologic outcomes, and complications of thermal ablation (TA versus partial nephrectomy (PN in management of Small renal masses (SRMs in solitary kidney.Medline, Embase, Web of Science and the Cochrane Library were systematically searched. A meta-analysis for comparative studies comparing TA with PN was performed. According to predefined inclusion criteria, seven datasets were identified from 8 observational studies including a total of 628 patients. Cumulated data showed the changes of creatinine (p=0.02 and estimated glomerular filtration rate (eGFR (p<0.0001 in TA arm were significantly less than these in PN arm. Significantly less new-set chronic kidney disease (CKD was observed in TA group (p=0.04. In terms of postoperative dialysis rate, the difference favoring TA was also noted, though there is no statistical significance (p=0.09. With regard to perioperative outcomes, our data demonstrated that patients who underwent TA had significantly shorter operation time (p=0.002, less blood loss (p<0.0001, shorter length of stay (p<0.00001, and less transfusion rate (p=0.01 than those underwent PN. In addition, patients underwent TA suffered less intra- and postoperative complications (p=0.007, p<0.00001; respectively. With regard to oncologic outcomes, disease-free survival (DFS (p<0.00001 and cancer-specific survival (CSS (p=0.01 in the PN arm were significantly better than these of the TA arm. But, TA yielded a comparable overall survival to PN (p=0.40. Sensitivity analyses led to very similar results with overall results, and confirmed its stability.Our analysis indicates that PN have advantage in controlling cancer recurrence. However, TA is associated with significantly better renal functional preservation and perioperative outcomes, and less complications without increasing overall death. Our data suggest that indication for TA may be extended to select younger

  3. Efficacy of ultrasonography-guided renal biopsy for the evaluation of renal dysfunction following renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Jae; Choi, Chul Soon; Min, Seon Jeong; Lee, Gyung Kyu; Lee, Eil Seong; Kang, Ik Won; Bae, Sang Hoon [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

    2003-12-15

    To evaluate the usefulness and complications of renal biopsy under ultrasonography-guidance in renal dysfunction after renal transplantation. Ultrasonography-guided renal biopsy was done in 47 patients with the transplanted kidney. The subjects consisted of 30 males and 17 females, age ranged from 16 to 66 years (average age=38 years). Biopsies were done once in 27 patients, twice in 17 patients, three times in 3 patients, a total of 70 biopsies. The success rate of renal biopsy for the accurate pathologic diagnosis and the incidence and types of complications following biopsy were evaluated. The success rate of renal biopsy for the accurate pathologic diagnosis was 96%(67/70). Pathologic diagnosis included 27 cases of acute rejection (39%), 8 cases of acute tubular necrosis (11%), 4 cases of acute rejection and acute tubular necrosis (6%), 4 cases of cyclosporin toxicity (6%), 4 cases of primary disease recurrence (6%), 4 cases of infection (6%) and others. Complications after renal biopsy included 15 cases of microscopic hematuria (21%), 1 case of gross hematuria with spontaneous cessation and 1 case of life threatening hemorrhage. Ultrasonography-guided renal biopsy is a safe and effective diagnostic method for the evaluation of renal dysfunction following renal transplantation.

  4. Comparative Transcriptome Analysis of a Toxin-Producing Dinoflagellate Alexandrium catenella and Its Non-Toxic Mutant

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2014-11-01

    Full Text Available The dinoflagellates and cyanobacteria are two major kingdoms of life producing paralytic shellfish toxins (PSTs, a large group of neurotoxic alkaloids causing paralytic shellfish poisonings around the world. In contrast to the well elucidated PST biosynthetic genes in cyanobacteria, little is known about the dinoflagellates. This study compared transcriptome profiles of a toxin-producing dinoflagellate, Alexandrium catenella (ACHK-T, and its non-toxic mutant form (ACHK-NT using RNA-seq. All clean reads were assembled de novo into a total of 113,674 unigenes, and 66,812 unigenes were annotated in the known databases. Out of them, 35 genes were found to express differentially between the two strains. The up-regulated genes in ACHK-NT were involved in photosynthesis, carbon fixation and amino acid metabolism processes, indicating that more carbon and energy were utilized for cell growth. Among the down-regulated genes, expression of a unigene assigned to the long isoform of sxtA, the initiator of toxin biosynthesis in cyanobacteria, was significantly depressed, suggesting that this long transcript of sxtA might be directly involved in toxin biosynthesis and its depression resulted in the loss of the ability to synthesize PSTs in ACHK-NT. In addition, 101 putative homologs of 12 cyanobacterial sxt genes were identified, and the sxtO and sxtZ genes were identified in dinoflagellates for the first time. The findings of this study should shed light on the biosynthesis of PSTs in the dinoflagellates.

  5. Comparative ovarian microarray analysis of juvenile hormone-responsive genes in water flea Daphnia magna: potential targets for toxicity.

    Science.gov (United States)

    Toyota, Kenji; Williams, Timothy D; Sato, Tomomi; Tatarazako, Norihisa; Iguchi, Taisen

    2017-03-01

    The freshwater zooplankton Daphnia magna has been extensively employed in chemical toxicity tests such as OECD Test Guidelines 202 and 211. Previously, it has been demonstrated that the treatment of juvenile hormones (JHs) or their analogues to female daphnids can induce male offspring production. Based on this finding, a rapid screening method for detection of chemicals with JH-activity was recently developed using adult D. magna. This screening system determines whether a chemical has JH-activity by investigating the male offspring inducibility. Although this is an efficient high-throughput short-term screening system, much remains to be discovered about JH-responsive pathways in the ovary, and whether different JH-activators act via the same mechanism. JH-responsive genes in the ovary including developing oocytes are still largely undescribed. Here, we conducted comparative microarray analyses using ovaries from Daphnia magna treated with fenoxycarb (Fx; artificial JH agonist) or methyl farnesoate (MF; a putative innate JH in daphnids) to elucidate responses to JH agonists in the ovary, including developing oocytes, at a JH-sensitive period for male sex determination. We demonstrate that induction of hemoglobin genes is a well-conserved response to JH even in the ovary, and a potential adverse effect of JH agonist is suppression of vitellogenin gene expression, that might cause reduction of offspring number. This is the first report demonstrating different transcriptomics profiles from MF and an artificial JH agonist in D. magna ovary, improving understanding the tissue-specific mode-of-action of JH. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Less gastrointestinal toxicity after adjuvant radiotherapy on a small pelvic field compared to a standard pelvic field in patients with endometrial carcinoma

    NARCIS (Netherlands)

    de Jong, Renske A.; Pras, Elisabeth; Boezen, H. Marike; van der Zee, Ate G. J.; Mourits, Marian J. E.; Arts, Henriette J. G.; Aalders, Jan G.; Slot, Annerie; Timmer, Paul R.; Hollema, Harry; Nijman, Hans W.

    2012-01-01

    Objective: Radiotherapy is associated with short-term and long-term morbidity. This study compared toxicity rates among patients with endometrial carcinoma (EC) treated with adjuvant external beam radiation therapy (EBRT) on a small pelvic field (SmPF) in comparison with a standard pelvic field (StP

  7. Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Harper, Bryan [Oregon State University (United States); Thomas, Dennis; Chikkagoudar, Satish; Baker, Nathan [Pacific Northwest National Laboratory (United States); Tang, Kaizhi [Intelligent Automation, Inc. (United States); Heredia-Langner, Alejandro [Pacific Northwest National Laboratory (United States); Lins, Roberto [CPqAM, Oswaldo Cruz Foundation, FIOCRUZ-PE (Brazil); Harper, Stacey, E-mail: stacey.harper@oregonstate.edu [Oregon State University (United States)

    2015-06-15

    The integration of rapid assays, large datasets, informatics, and modeling can overcome current barriers in understanding nanomaterial structure–toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here, we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality in developing embryonic zebrafish, were established at realistic exposure levels and used to develop a hazard ranking of diverse nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both the core composition and outermost surface chemistry of nanomaterials. The resulting clusters guided the development of a surface chemistry-based model of gold nanoparticle toxicity. Our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. Research should continue to focus on methodologies for determining nanomaterial hazard based on multiple sub-lethal responses following realistic, low-dose exposures, thus increasing the availability of quantitative measures of nanomaterial hazard to support the development of nanoparticle structure–activity relationships.

  8. Renal-sparing strategies in cardiac transplantation

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Ross, Heather J

    2009-01-01

    PURPOSE OF REVIEW: Renal dysfunction due to calcineurin inhibitor (CNI) toxicity is a major clinical problem in cardiac transplantation. The aim of the article is to review the efficacy and safety of various renal sparing strategies in cardiac transplantation. RECENT FINDINGS: Small studies have...... documented that late initiation of CNI is safe in patients treated with induction therapy at the time of transplantation. Use of mycophenolate is superior when compared with azathioprine to allow for CNI reduction. More substantial reduction in CNI levels is safe and effective with the introduction...... of sirolimus or everolimus. However, studies that use very early CNI discontinuation have found an increased risk of allograft rejection, and this strategy requires further study before it can be routinely recommended. CNI discontinuation late after cardiac transplantation seems more effective than CNI...

  9. Sunitinib for advanced renal cell cancer

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2008-03-01

    Full Text Available Chris CoppinBC Cancer Agency and University of British Columbia, Vancouver, CanadaAbstract: Renal cell cancer has been refractory to drug therapy in the large majority of patients. Targeted agents including sunitinib have been intensively evaluated in renal cell cancer over the past 5 years. Sunitinib is an oral small molecule inhibitor of several targets including multiple tyrosine kinase receptors of the angiogenesis pathway. This review surveys the rationale, development, validation, and clinical use of sunitinib that received conditional approval for use in North America and Europe in 2006. In patients with the clear-cell subtype of renal cell cancer and metastatic disease with good or moderate prognostic factors for survival, sunitinib 50 mg for 4 weeks of a 6-week cycle provides superior surrogate and patient-reported outcomes when compared with interferon-alfa, the previous commonly used first-line drug. Overall survival has not yet shown improvement over interferon and is problematic because of patient crossover from the control arm to sunitinib at disease progression. Toxicity is significant but manageable with experienced monitoring. Sunitinib therapy is an important step forward for this condition. High cost and limited efficacy support the ongoing search for further improved therapy.Keywords: renal cell cancer, targeted therapy, sunitinib

  10. Comparative toxicities and pharmacokinetics of intrathecal lipid (amphotericin B colloidal dispersion) and conventional deoxycholate formulations of amphotericin B in rabbits.

    Science.gov (United States)

    Clemons, K V; Sobel, R A; Williams, P L; Stevens, D A

    2001-02-01

    The lipid formulation of amphotericin B, Amphotec (ABCD), has not been used intrathecally. After a single intrathecal dose or after four doses, conventionally formulated deoxycholate amphotericin B (AMB) (Fungizone) resulted in higher levels of amphotericin B in the cerebrospinal fluid of rabbits than did ABCD. Clinically and histologically, ABCD was about threefold less toxic than AMB after a single dose and 3- to 30-fold less toxic after multiple dosing. These data are encouraging for the potential use of ABCD as an intrathecal treatment.

  11. Preliminary comparing the toxicities of the hybrid cry1Acs fused with different heterogenous genes provided guidance for the fusion expression of Cry proteins.

    Science.gov (United States)

    Tang, Ying; Tong, Jinying; Zhang, Yunlei; Wang, Lei; Hu, Shengbiao; Li, Wenping; Lv, Yuan

    2012-01-01

    In order to provide guidance for selecting suitable heterogenous gene that can efficiently enhance toxicity or broaden insecticidal spectrum of Cry1Ac through fusion expression, two hybrid cry1Acs fused with chitinase-encoding gene tchiB and neurotoxin gene hwtx-1 respectively were constructed and their toxicities were compared. A Bacillus thuringiensis strain harboring the cry1Ac gene in vector pHT315 was used as control. Bioassay revealed that LC(50) (after 72 h) of Cry1Ac protoxin was 41.01 μg mL(-1), while the hybrid cry1Acs fused with tchiB and hwtx-1 were 4.89 and 23.14 μg mL(-1), which were 8.23- and 1.77-fold higher than Cry1Ac protoxin in terms of relative toxicity respectively. Both fusion crystals had a higher toxicity than the original Cry1Ac protein and the toxicity of hybrid cry1Acs fused with hwtx-1 experienced a more significant increase than that fused with tchiB.

  12. Renal perfusion scintiscan

    Science.gov (United States)

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  13. Parallel comparative studies on the toxic effects of unmodified CdTe quantum dots, gold nanoparticles, and carbon nanodots on live cells as well as green gram sprouts.

    Science.gov (United States)

    Song, Yanchao; Feng, Duan; Shi, Wen; Li, Xiaohua; Ma, Huimin

    2013-11-15

    By using confocal fluorescence microscopy and direct visualization, a parallel comparative investigation has been systematically made on the relative toxicity of three common nanomaterials, such as unmodified CdTe quantum dots (QDs), Au nanoparticles (Au NPs) and carbon nanodots (C-dots), to live cells as well as green gram sprouts. Bare CdTe QDs exert the most toxic effect on a variety of cell lines (HeLa, MCF-7, NIH/3T3 cells) as well as live plants (green gram sprouts). For cells, this toxic effect leads to the partial death of cells, the decrease of cell metabolic activity, the shrinkage of cells, the breakage of chromatin, the damage of cell membrane integrity, and the fragmentation of mitochondria; for green gram sprouts, the presence of CdTe QDs markedly inhibits their growth. Moreover, the toxic behaviors of CdTe QDs are dose- and time-dependent. Under the same conditions, Au NPs only decrease the metabolic activity of cells to a small extent, and do not affect the appearance of cellular/subcellular structures and the plant growth; interestingly, C-dots exert no obvious toxicity to both live cells and the growth of green gram sprouts, showing good biocompatibility. These parallel comparative studies clearly reveal that the relative toxicity of the three nanomaterials in their native forms is bare CdTe QDs>Au NPs>C-dots, whose IC50 values for normal NIH/3T3 cells are 0.98 μg/mL, 62 μg/mL, and >250 μg/mL, respectively. This quantitative information is of great importance for right choice of the nanomaterials in their practical applications.

  14. Long-Term Effects of a Very Low Carbohydrate Compared With a High Carbohydrate Diet on Renal Function in Individuals With Type 2 Diabetes: A Randomized Trial.

    Science.gov (United States)

    Tay, Jeannie; Thompson, Campbell H; Luscombe-Marsh, Natalie D; Noakes, Manny; Buckley, Jonathan D; Wittert, Gary A; Brinkworth, Grant D

    2015-11-01

    To compare the long-term effects of a very low carbohydrate, high-protein, low saturated fat (LC) diet with a traditional high unrefined carbohydrate, low-fat (HC) diet on markers of renal function in obese adults with type 2 diabetes (T2DM), but without overt kidney disease.One hundred fifteen adults (BMI 34.6 ± 4.3 kg/m, age 58 ± 7 years, HbA1c 7.3 ± 1.1%, 56 ± 12 mmol/mol, serum creatinine (SCr) 69 ± 15 μmol/L, glomerular filtration rate estimated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFR 94 ± 12 mL/min/1.73 m)) were randomized to consume either an LC (14% energy as carbohydrate [CHO diet combined with supervised exercise training (60 min, 3 day/wk) for 12 months. Body weight, blood pressure, and renal function assessed by eGFR, estimated creatinine clearance (Cockcroft-Gault, Salazar-Corcoran) and albumin excretion rate (AER), were measured pre- and post-intervention.Both groups achieved similar completion rates (LC 71%, HC 65%) and reductions in weight (mean [95% CI]; -9.3 [-10.6, -8.0] kg) and blood pressure (-6 [-9, -4]/-6[-8, -5] mmHg), P ≥ 0.18. Protein intake calculated from 24 hours urinary urea was higher in the LC than HC group (LC 120.1 ± 38.2 g/day, 1.3 g/kg/day; HC 95.8 ± 27.8 g/day, 1 g/kg/day), P diet effect. Changes in SCr (LC 3 [1, 5], HC 1 [-1, 3] μmol/L) and eGFR (LC -4 [-6, -2], HC -2 [-3, 0] mL/min/1.73 m) did not differ between diets (P = 0.25). AER decreased independent of diet composition (LC --2.4 [-6, 1.2], HC -1.8 [-5.4, 1.8] mg/24 h, P = 0.24); 6 participants (LC 3, HC 3) had moderately elevated AER at baseline (30-300 mg/24 h), which normalized in 4 participants (LC 2, HC 2) after 52 weeks.Compared with a traditional HC weight loss diet, consumption of an LC high protein diet does not adversely affect clinical markers of renal function in obese adults with T2DM and no preexisting kidney disease.

  15. Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents.

    Science.gov (United States)

    Chen, Rui; Ling, Daishun; Zhao, Lin; Wang, Shuaifei; Liu, Ying; Bai, Ru; Baik, Seungmin; Zhao, Yuliang; Chen, Chunying; Hyeon, Taeghwan

    2015-12-22

    Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents.

  16. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jing [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States); Parsons, Loren [Committee on Neurobiology of Affective Disorders, The Scripps Research Institute, La Jolla, CA (United States); Pope, Carey, E-mail: carey.pope@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States)

    2013-11-01

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

  17. Ciprofloxacin-Induced Renal Failure

    Directory of Open Access Journals (Sweden)

    Audra Fuller

    2015-10-01

    Full Text Available Acute renal failure (ARF is a common diagnosis in hospitalized patients, particularly in intensive care units (ICU. Determining the cause and contributing factors associated with ARF is crucial during treatment. The etiology is complex, and several factors often contribute to its development. Medications can cause acute tubular necrosis, acute interstitial nephritis, and crystal-induced or post-obstructive nephropathy. There have been several case reports of ARF secondary to fluoroquinolones. Here we report the development of acute renal failure within a few days of initiating oral ciprofloxacin therapy and briefly describe the different types of renal failure secondary to fluoroquinolone administration. Clinical studies demonstrate that using fluoroquinolones with other potentially nephrotoxic medications requires monitoring of renal function to limit the renal toxicity with these medications. Also, the risk-benefit profile of patients requiring fluoroquinolones should be considered.

  18. Children of non-Western origin with end-stage renal disease in the Netherlands, Belgium and a part of Germany have impaired health-related quality of life compared with Western children

    NARCIS (Netherlands)

    Schoenmaker, N.J.; Haverman, L.; Tromp, W.F.; Lee, J.H. van der; Offringa, M.; Adams, B.; Bouts, A.H.M.; Collard, L.; Cransberg, K.; Dyck, M. van; Godefroid, N.; Hoeck, K. van; Koster-Kamphuis, L.; Lilien, M.R.; Raes, A.; Taylan, C.; Grootenhuis, M.A.; Groothoff, J.W.

    2014-01-01

    BACKGROUND: Many children with end-stage renal disease (ESRD) living in Western Europe are of non-Western European origin. They have unfavourable somatic outcomes compared with ESRD children of Western origin. In this study, we compared the Health-related Quality of Life (HRQoL) of both groups. METH

  19. RADAR – A randomised, multi-centre, prospective study comparing best medical treatment versus best medical treatment plus renal artery stenting in patients with haemodynamically relevant atherosclerotic renal artery stenosis

    Directory of Open Access Journals (Sweden)

    Hauk Michael

    2009-07-01

    Full Text Available Abstract Background Prospective, international, multi-centre, randomised (1:1 trial to evaluate the clinical impact of percutaneous transluminal renal artery stenting (PTRAS on the impaired renal function measured by the estimated glomerular filtration rate (eGFR in patients with haemodynamically significant atherosclerotic renal artery stenosis. Methods Patients will be randomised to receive either PTRAS using the Dynamic Renal Stent system plus best medical treatment or best medical treatment. Renal stenting will be performed under angiographic imaging. For patients randomised to best medical treatment the degree of stenosis measured by renal duplex sonography (RDS will be confirmed by MR angio or multi-slice CT where possible. Best medical treatment will be initiated at randomisation or post procedure (for PTRAS arm only, and adjusted as needed at all visits. Best medical treatment is defined as optimal drug therapy for control of the major risk factors (blood pressure ≤ 125/80 mmHg, LDL cholesterol ≤ 100 mg/dL, HbA1c ≤ 6.5%. Data recordings include serum creatinine values, eGFR, brain natriuretic peptide, patients' medical history and concomitant medication, clinical events, quality of life questionnaire (SF-12v2™, 24 hour ambulatory blood pressure measurement, renal artery duplex ultrasound and echocardiography. Follow-up intervals are at 2, 6, 12 and 36 months following randomisation. The primary endpoint is the difference between treatments in change of eGFR over 12 months. Major secondary endpoints are technical success, change of renal function based on the eGFR slope change between pre-treatment and post-treatment (i.e. improvement, stabilisation, failure, clinical events overall such as renal or cardiac death, stroke, myocardial infarction, hospitalisation for congestive heart failure, progressive renal insufficiency (i.e. need for dialysis, need of target vessel revascularisation or target lesion revascularisation, change in

  20. Modifying cyclosporine associated renal allograft dysfunction

    Directory of Open Access Journals (Sweden)

    Mohapatra N

    2009-01-01

    Full Text Available Transplantation is accepted therapy for chronic kidney disease. However the essential immuno-suppressive agents for graft survival have their own side-effects. Renal biopsy is a reliable tool for diagnosing cyclosporine (CsA nephrotoxicity. To present our observations on CsA toxicity in renal allograft biopsies, we studied prospectively 207 renal allograft biopsies performed for graft dysfunction as per Ahmedabad Tole-rance Induction Protocol (ATIP and compared them to 50 controls from January to October 2007. The ATIP comprised donor specific leucocyte infusions, low dose target specific irradiation; non-myeloablative condi-tioning with Anti-T ± B cell antibodies followed by intraportal administration of cultured donor bone marrow (BM ± adipose tissue derived mesenchymal stem cells. Renal transplantation was performed following nega-tive lymphocytotoxicity cross-matching. The post-transplant immunosuppressive agents included CsA 2.5 ± 0.5 mg/kg BW/day and prednisone 0.2 mg/kg BW/day. The controls were transplanted using standard triple immunosuppressive agents including CsA 5 ± 1 mg/Kg BW/day, prednisone 0.6 mg/kg BW/day, and MMF/ Azathioprine. The Institutional Review Board approved the ATIP. The biopsies were categorized into 2 groups; group A (N=97: performed < 6 months, group B (N= 160, > 6 months posttransplant. Acute CsA toxicity was observed in group A: 2.5% ATIP and 11.1% controls; group B: 16.2% ATIP and 8.8% controls. Chronic CsA toxicity was observed in group B: 10.8 % ATIP and 17.6 % controls. Acute toxicity was more in the ATIP, while chronic toxicity was more in the controls. CsA doses were reduced post-biopsy and resulted in improved graft function evaluated by serum creatinine. We conclude that CsA nephrotoxicity evaluated by allograft biopsy resulted in allograft function recovery by decreasing the cyclosporine dose, and the ATIP decreased the incidence of CsA nephrotoxicity.

  1. Anatomy of the collecting system of lower pole of the kidney in patients with a single renal stone: a comparative study with individuals with normal kidneys

    Directory of Open Access Journals (Sweden)

    Zomorrodi Afshar

    2010-01-01

    Full Text Available At least 5% of women and 12% of men during their lives will experience renal colic, at least once. Many theories have been suggested for the etiology of renal stones and va-riations in the anatomy of the collecting system have been suggested to have a role in stone formation. This study was conducted to examine the role of variation of lower pole collecting system in patients with lower pole kidney stone and compared the same in normal persons (kidney donors. Investigation for the anatomy of the lower pole of the kidney (angle between lower infundibulum and pelvis, length and diameter of the infundibulum and number and pattern distribution of calyces was carried out using intravenous pyelogram (IVP in 100 cases with urinary stone (study cases and 400 persons with normal kidneys (control subjects. The study was a retrospective cross-sectional case control study. Results were analyzed by Mann-Whiteny and independent sample chi square tests. The mean infundibulum-pelvic angle (IPA in control subjects and in patients was 112.5 ± 10.7 and 96.6 ± 28.8, respectively. There was significant correlation between reduced angle and stone formation (P= < 0.001. The mean infundibulum-uretero-pelvic angle (IUPA in control subjects and study cases was 53.5 ± 12.7 and 42.6 ± 13.4, respectively. There was significant correlation between decreased angle and stone formation (P= < 0.001. The mean length of infundibulum of lower pole of kidney (IPIL in controls and study patients was 22.5 ± 4.1 and 27.5 ± 7.7, respectively, which was statistically significant (P< 0.001. The mean number of calyces in lower pole of the kidney (LPCN in controls and study patients was 2.6 ± 0.6 and 3 ± 0.9, respectively, which was statistically significant (P= < 0.002. There was no significant correlation between distribution of calyces and stone formation (P= 0.366. Our study suggests that abnormal renal anatomy was more common in patients with lower pole kidney stone and should

  2. Anatomy of the collecting system of lower pole of the kidney in patients with a single renal stone: a comparative study with individuals with normal kidneys.

    Science.gov (United States)

    Zomorrodi, Afshar; Buhluli, Abulfazel; Fathi, Samad

    2010-07-01

    At least 5% of women and 12% of men during their lives will experience renal colic, at least once. Many theories have been suggested for the etiology of renal stones and variations in the anatomy of the collecting system have been suggested to have a role in stone formation. This study was conducted to examine the role of variation of lower pole collecting system in patients with lower pole kidney stone and compared the same in normal persons (kidney donors). Investigation for the anatomy of the lower pole of the kidney (angle between lower infundibulum and pelvis, length and diameter of the infundibulum and number and pattern distribution of calyces) was carried out using intravenous pyelogram (IVP) in 100 cases with urinary stone (study cases) and 400 persons with normal kidneys (control subjects). The study was a retrospective cross-sectional case control study. Results were analyzed by Mann-Whitney and independent sample chi square tests. The mean infundibulum-pelvic angle (IPA) in control subjects and in patients was 112.5 +/- 10.7 and 96.6 +/- 28.8, respectively. There was significant correlation between reduced angle and stone formation (P= kidney (IPIL) in controls and study patients was 22.5 +/- 4.1 and 27.5 +/- 7.7, respectively, which was statistically significant (Pkidney (LPCN) in controls and study patients was 2.6 +/- 0.6 and 3 +/- 0.9, respectively, which was statistically significant (P = or kidney stone and should be considered a risk factor for forming lower pole kidney stone.

  3. Comparative toxicity study on classical and modified version of Jawarish Jalinoos (a traditional Unani formulation in rats

    Directory of Open Access Journals (Sweden)

    Gulam Mohammed Husain

    2017-03-01

    Conclusion: The 90-day repeated dose oral toxicity study demonstrates that the no observed adverse effect level of SFJJ and JJ is greater than 2024 mg/kg bw/d and 2000 mg/kg bw/d (p.o. in rats, respectively. Both formulations were found to be safe up to the tested dose levels and experimental conditions, and therefore safe for clinical use as specified in the literature.

  4. Comparative acute systemic toxicity of several quinoxaline 1,4-di-N-oxides in Wistar rats.

    Science.gov (United States)

    Azqueta, Amaya; Gil, Ana Gloria; García-Rodríguez, Alba; García-Jalón, Jose Antonio; Cia, Felipe; Zarranz, Belén; Monge, Antonio; de Cerain, Adela López

    2007-01-01

    The acute toxicity of six quinoxaline 1,4-di-N-oxides has been evaluated in an attempt to determine: a) the feasibility of testing systemic toxicity of these compounds in a very preliminary phase without an adequate formulation for in vivo administration, b) the LD50 range and the toxic target organ of these compounds in order to have an approximation of the structure-activity relationship. Quinoxaline 1,4-di-N-oxides have shown a great variety of biological activities with potential therapeutic application in cancer, malaria, etc. Problems of toxicity hinder the progression of these compounds to clinical phases. The compounds dissolved in DMSO at their solubility limit were administered i.v. to female Wistar rats (8 weeks, 160 g), using an infusion pump (300 microL; 20 microl/min). Animals were observed for a period of 14 days. This dose of the vehicle (1.7 ml/kg) was well tolerated by the animals. The LD50 could not be determined, but a marked hypoactivity was induced by the treatment. The same compounds were also injected intraperitoneally, suspended in 0.01% Tween 80/0.09 % saline, and the animals that did not die were observed for a period of 14 days. The LD50 could be estimated to be in a range between 30 and 120 mg/kg, except for one of the compounds. A decrease in the evolution of body weight and hypoactivity were the principal symptoms induced by the treatment. In both assays, histopathologic study of heart, liver, kidney, lung, spleen and ovaries indicated that the target organs may be heart and spleen. In conclusion, the i.v. route is not adequate for estimating the LD50 of these compounds due to solubility problems; by i.p. route, the LD50 interval is between 30 and 120 mg/kg. The data did not permit the deduction of any specific structure-activity relationship.

  5. A comparative study on characterization of textile wastewaters (untreated and treated) toxicity by chemical and biological tests.

    Science.gov (United States)

    Sharma, K P; Sharma, S; Sharma, Subhasini; Singh, P K; Kumar, S; Grover, R; Sharma, P K

    2007-08-01

    Toxicity of textile wastewaters (untreated and treated) and their ingredient chemicals was quantified in terms of their chemical characteristics, fish (Gambusia affinis) mortality and end point growth responses of duckweed (Lemna aequinoctialis) in short-term bioassays. Other parameters of fish bioassay were erythrocyte morphology and its counts. Despite of a definite correlation between data of biological tests (LC/EC(50) values) with that of chemical tests, biological tests were found to be relatively more sensitive to both wastewaters and ingredient chemicals. Amongst all the examined parameters of test organisms, fish RBCs (morphology and counts) sensitivity to pollutants in the wastewaters was usually maximum and therefore, their study should be included in the routine fish bioassay. Other advantage of biological test such as on Lemna is even detection of eutrophic potential of wastewaters, as noted at their higher dilutions. The ingredient chemicals (major) contributing maximum toxicity to textile dye wastewater were, acids (HCl and H(2)SO(4)), alkali (Na(2)O SiO(2)), salt (NaNO(2)) and heavy metal (Cu), whereas dyes (4) were relatively less toxic.

  6. A Comparative Study of Two Quantum Chemical Descriptors in Predicting Toxicity of Aliphatic Compounds towards Tetrahymena pyriformis

    Directory of Open Access Journals (Sweden)

    Altaf Hussain Pandith

    2010-01-01

    Full Text Available Quantum chemical parameters such as LUMO energy, HOMO energy, ionization energy (I, electron affinity (A, chemical potential (μ, hardness (η electronegativity (χ, philicity (ωα, and electrophilicity (ω of a series of aliphatic compounds are calculated at the B3LYP/6-31G(d level of theory. Quantitative structure-activity relationship (QSAR models are developed for predicting the toxicity (pIGC50 of 13 classes of aliphatic compounds, including 171 electron acceptors and 81 electron donors, towards Tetrahymena pyriformis. The multiple linear regression modeling of toxicity of these compounds is performed by using the molecular descriptor log P (1-octanol/water partition coefficient in conjunction with two other quantum chemical descriptors, electrophilicity (ω and energy of the lowest unoccupied molecular orbital (ELUMO. A comparison is made towards the toxicity predicting the ability of electrophilicity (ω versus ELUMO as a global chemical reactivity descriptor in addition to log P. The former works marginally better in most cases. There is a slight improvement in the quality of regression by changing the unit of IGC50 from mg/L to molarity and by removing the racemates and the diastereoisomers from the data set.

  7. 不同检测系统测定血清肾功、血糖、淀粉酶结果对比分析%Comparative Analysis of Serum Renal Function, Blood Glucose and Amylase in Different Detection Systems

    Institute of Scientific and Technical Information of China (English)

    徐新生

    2015-01-01

    Objective To compare the detection results of renal function,blood sugar and amylase based on dif erent systems.Methods 300 serum samples col ected from our Clinical Laboratory were tested by two systems.The levels of renal function,blood sugar and amylase were compared.Results Based on the dif erent detection systems,the levels of renal function,blood sugar and amylase were not dif erent ( 0.05);不同检测系统在肌酐、血糖及淀粉酶测定的精密度无差异;结论两种检测系统对肾功、血糖及淀粉酶测定结果具有可比性,测定的精密度较高,能够满足临床使用要求。

  8. BAP1 is overexpressed in black compared with white patients with Mx-M1 clear cell renal cell carcinoma: A report from the cancer genome atlas.

    Science.gov (United States)

    Paulucci, David J; Sfakianos, John P; Yadav, Shalini Singh; Badani, Ketan K

    2016-06-01

    Incidence of renal cell carcinoma (RCC) is higher in Black patients with disease-specific and overall survival being lower compared with White patients even though renal tumors among Black patients are more likely to be localized. These disparities have been attributed to higher rates of obesity and hypertension, lower rates of nephrectomy, and a lack of access to quality health care. With scant genomic evidence to account for these disparities, the present study sought to compare BAP1 expression between Black and White patients with clear cell RCC (ccRCC); a gene that inhibits tumor progression when overexpressed and results in poor clinical outcomes when silenced. The cancer genome atlas dataset was used to identify 58 (9.9%) Black and 529 (90.9%) White patients with ccRCC with an initial pathologic diagnosis from 1998 to 2013. BAP1 expression was compared using a Mann-Whitney U test. The association between BAP1 expression and pathologic stage, American Joint Committee on Cancer (AJCC) stage, and Fuhrman grade was assessed for the overall cohort and stratified by race. The association between BAP1 expression and overall survival was assessed using Cox proportion hazards models adjusting for Fuhrman grade, pathologic stage, and the presence of pathologic metastases for the overall cohort and stratified by race. The level of BAP1 expression was significantly higher in Black vs. White patients with ccRCC (10.5 vs. 10.3; P<.001). For the overall cohort, increasing BAP1 expression was associated with decreasing pathologic stage (β =-0.25, P = .004) and decreasing AJCC stage (β =-0.029, P = .006). For Black patients, increasing BAP1 expression was associated with decreasing AJCC stage (β =-0.79, P = .016), decreasing Fuhrman grade (β =-0.55, P = .011), and a decreased risk of pathologic metastases (odds ratio [OR] = 0.83, P = .038). For White patients, increasing BAP1 expression was associated with decreasing pathologic stage (β =-0.20, P = .026). BAP1 is

  9. Hyperthyroidism in a renal transplant recipient.

    Science.gov (United States)

    Peces, R; Navascués, R A; Baltar, J; Laurés, A S; Ortega, F; Alvarez-Grande, J

    1998-01-01

    We report a case of toxic multinodular goiter with severe symptomatic hyperthyroidism in a female diagnosed 5 months after successful renal transplantation. To our knowledge, this is the first well-documented case of hyperthyroidism in a renal transplant recipient that responded well to methimazole. Special attention should be made to the use of methimazole and the possible interaction with immunosuppressive drugs.

  10. The rate of progression of renal disease may not be slower in women compared with men : a patient-level meta-analysis

    NARCIS (Netherlands)

    Jafar, TH; Schmid, CH; Stark, PC; Toto, R; Remuzzi, G; Ruggenenti, P; Marcantoni, C; Becker, G; Shahinfar, S; de Jong, PE; de Zeeuw, D; Kamper, AL; Strangaard, S; Levey, AS

    2003-01-01

    Background. Some studies suggest that progression of renal disease is slower in women than in men. However, other factors that are also associated with progression of renal disease have not always been taken into account. Therefore, we undertook this analysis to explore the independent association o

  11. Comparative performance of descriptors in a multiple linear and Kriging models: a case study on the acute toxicity of organic chemicals to algae.

    Science.gov (United States)

    Tugcu, Gulcin; Yilmaz, H Birkan; Saçan, Melek Türker

    2014-10-01

    This study presents quantitative structure-toxicity relationship (QSTR) models on the toxicity of 91 organic compounds to Chlorella vulgaris using multiple linear regression (MLR) and Kriging techniques. The molecular descriptors were calculated using SPARTAN and DRAGON programs, and descriptor selection was made by "all subset" method available in the QSARINS software. MLR and Kriging models developed with the same descriptors were compared. In addition to these models, Kriging method was used for descriptor selection, and model development. The selected descriptors showed the importance of hydrophobicity, molecular weight and atomic ionization state in describing the toxicity of a diverse set of chemicals to C. vulgaris. A QSTR model should be associated with appropriate measures of goodness-of-fit, robustness, and predictivity in order to be used for regulatory purpose. Therefore, while the internal performances (goodness-of-fit and robustness) of the models were determined by using a training set, the predictive abilities of the models were determined by using a test set. The results of the study showed that while MLR method is easier to apply, the Kriging method was more successful in predicting toxicity.

  12. The comparative toxicity of a reduced, crude comfrey (Symphytum officinale) alkaloid extract and the pure, comfrey-derived pyrrolizidine alkaloids, lycopsamine and intermedine in chicks (Gallus gallus domesticus).

    Science.gov (United States)

    Brown, Ammon W; Stegelmeier, Bryan L; Colegate, Steven M; Gardner, Dale R; Panter, Kip E; Knoppel, Edward L; Hall, Jeffery O

    2016-05-01

    Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recommended comfrey be used for external use only. However, in many locations comfrey continues to be ingested as a tisane or as a leafy vegetable. The objective of this work was to compare the toxicity of a crude, reduced comfrey alkaloid extract to purified lycopsamine and intermedine that are major constituents of S. officinale. Male, California White chicks were orally exposed to daily doses of 0.04, 0.13, 0.26, 0.52 and 1.04 mmol lycopsamine, intermedine or reduced comfrey extract per kg bodyweight (BW) for 10 days. After another 7 days chicks were euthanized. Based on clinical signs of poisoning, serum biochemistry, and histopathological analysis the reduced comfrey extract was more toxic than lycopsamine and intermedine. This work suggests a greater than additive effect of the individual alkaloids and/or a more potent toxicity of the acetylated derivatives in the reduced comfrey extract. It also suggests that safety recommendations based on purified compounds may underestimate the potential toxicity of comfrey.

  13. [Influence of extracorporeal shock wave lithotripsy (ESWL) on renal function assessed by 99mTc-DMSA scintigraphy: comparative analysis between ESWL and percutaneous nephroureterolithotripsy (PNL)].

    Science.gov (United States)

    Matsuura, H; Hioki, T; Sakurai, M; Arima, K; Yanagawa, M; Sugimura, Y; Tochigi, H; Kawamura, J; Kinoshita, N; Katoh, H

    1994-12-01

    99mTc-DMSA renal scintigraphy was utilized to investigate the influence of ESWL on renal function in comparison with that of PNL. In the beginning, the reproducibility of renal uptake rate by the scintigraphy was examined in eleven healthy volunteers under both non-diuretic and diuretic states. The renal uptake rate was shown to be sufficiently reproducible in the same person in the two different trials. However, the differences and the standard deviations were shown to be a few percentages, which were not statistically significant. Changes in the repeated renal uptake rate seem to indicate not only changes of renal function with the treatment but also some technical errors. Herein, to investigate changes in renal function of the therapeutic side, the uptake ratio rate (rate of uptake rate in the therapeutic side/uptake rate in the contral lateral side) was utilized instead of uptake rate. Renal scintigraphy was carried out in 48 patients with unilateral renal stones before and after ESWL or PNL monotherapy or the combined ESWL and PNL therapies. Within one week of treatment, the uptake ratio rate significantly decreased in patients with PNL or the combined ESWL and PNL, although DMSA uptake rate in the therapeutic side did not significantly changes. Neither renal uptake rate nor uptake ratio rate significantly changed after ESWL treatment. There was no significant difference in changes of uptake ratio rate between Siemens Lithostars Plus and the improved Dornier HM-3 lithotriptors. This study indicated that ESWL monotherapy did not affect the uptake ratio rate, although PNL monotherapy and the combined ESWL and PNL therapies may affect the uptake ratio rate to some extent.

  14. Cell-metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Milgram, S. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Carriere, M. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Thiebault, C. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Berger, P. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Khodja, H. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gouget, B. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)]. E-mail: barbara.gouget@cea.fr

    2007-07-15

    Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se{sup IV} and Cu as the most toxic and Ni, Se{sup VI}, Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS.

  15. Comparative in vitro toxicity profile of electronic and tobacco cigarettes, smokeless tobacco and nicotine replacement therapy products: e-liquids, extracts and collected aerosols.

    Science.gov (United States)

    Misra, Manoj; Leverette, Robert D; Cooper, Bethany T; Bennett, Melanee B; Brown, Steven E

    2014-10-30

    The use of electronic cigarettes (e-cigs) continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT) products and a nicotine replacement therapy (NRT) product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.

  16. Comparative In Vitro Toxicity Profile of Electronic and Tobacco Cigarettes, Smokeless Tobacco and Nicotine Replacement Therapy Products: E-Liquids, Extracts and Collected Aerosols

    Directory of Open Access Journals (Sweden)

    Manoj Misra

    2014-10-01

    Full Text Available The use of electronic cigarettes (e-cigs continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT products and a nicotine replacement therapy (NRT product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.

  17. Renal angiomyolipoma

    DEFF Research Database (Denmark)

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

    lesion. Three cases of renal angiomyolipoma, 2 of which underwent perfusion-fixation, were studied by electron microscopy to clarify the cellular composition of this lesion. In the smooth muscle cells abundant accumulation of glycogen was found, whereas the lipocytes disclosed normal ultrastructural......-specific vesicular structures. These findings suggest a secondary vascular damage, i.e. the thickened vessels may not be a primary, integral part of renal angiomyolipoma. Evidence of a common precursor cell of renal angiomyolipoma was not disclosed. It is concluded that renal angiomyolipoma is a hamartoma composed...

  18. Safety data on 19 vehicles for use in 1 month oral rodent pre-clinical studies: administration of hydroxypropyl-ß-cyclodextrin causes renal toxicity.

    Science.gov (United States)

    Healing, Guy; Sulemann, Tabassum; Cotton, Peter; Harris, Jayne; Hargreaves, Adam; Finney, Rowena; Kirk, Sarah; Schramm, Carolin; Garner, Clare; Pivette, Perrine; Burdett, Lisa

    2016-01-01

    Potential new drugs are assessed in pre-clinical in vivo studies to determine their safety profiles. The drugs are formulated in vehicles suitable for the route of administration and the physicochemical properties of the drug, aiming to achieve optimal exposure in the test species. The availability of safety data on vehicles is often limited (incomplete data, access restricted/private databases). Nineteen potentially useful vehicles that contained new and/or increased concentrations of excipients and for which little safety data have been published were tested. Vehicles were dosed orally once daily to HanWistar rats for a minimum of 28 days and a wide range of toxicological parameters were assessed. Only 30% (w/v) hydroxypropyl-ß-cyclodextrin was found unsuitable owing to effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased salivation and hence this vehicle should be used with caution. As 40% (v/v) tetraethylene glycol affected urinary parameters, its use should be carefully considered, particularly for compounds suspected to impact the renal system and studies longer than 1 month. There were no toxicologically significant findings with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v) Miglyol®812, 20% (w/v) Kolliphor®RH40, 10% (w/v) Poloxamer 407, 5% (w/v) polyvinylpyrrolidone K30 or 10% (v/v) Labrafil®M1944. All other vehicles tested caused isolated or low magnitude effects which would not prevent their use. The aim of sharing these data, including adverse findings, is to provide meaningful information for vehicle selection, thereby avoiding repetition of animal experimentation.

  19. Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ(9)-THC: mechanism underlying greater toxicity?

    Science.gov (United States)

    Fantegrossi, William E; Moran, Jeffery H; Radominska-Pandya, Anna; Prather, Paul L

    2014-02-27

    K2 or Spice products are emerging drugs of abuse that contain synthetic cannabinoids (SCBs). Although assumed by many teens and first time drug users to be a "safe" and "legal" alternative to marijuana, many recent reports indicate that SCBs present in K2 produce toxicity not associated with the primary psychoactive component of marijuana, ∆(9)-tetrahydrocannabinol (Δ(9)-THC). This mini-review will summarize recent evidence that use of K2 products poses greater health risks relative to marijuana, and suggest that distinct pharmacological properties and metabolism of SCBs relative to Δ(9)-THC may contribute to the observed toxicity. Studies reviewed will indicate that in contrast to partial agonist properties of Δ(9)-THC typically observed in vitro, SCBs in K2 products act as full cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) agonists in both cellular assays and animal studies. Furthermore, unlike Δ(9)-THC metabolism, several SCB metabolites retain high affinity for, and exhibit a range of intrinsic activities at, CB1 and CB2Rs. Finally, several reports indicate that although quasi-legal SCBs initially evaded detection and legal consequences, these presumed "advantages" have been limited by new legislation and development of product and human testing capabilities. Collectively, evidence reported in this mini-review suggests that K2 products are neither safe nor legal alternatives to marijuana. Instead, enhanced toxicity of K2 products relative to marijuana, perhaps resulting from the combined actions of a complex mixture of different SCBs present and their active metabolites that retain high affinity for CB1 and CB2Rs, highlights the inherent danger that may accompany use of these substances.

  20. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: liver effects.

    Science.gov (United States)

    Yoo, Hong Sik; Bradford, Blair U; Kosyk, Oksana; Shymonyak, Svitlana; Uehara, Takeki; Collins, Leonard B; Bodnar, Wanda M; Ball, Louise M; Gold, Avram; Rusyn, Ivan

    2015-01-01

    Trichloroethylene (TCE) is a widely used organic solvent. Although TCE is classified as carcinogenic to humans, substantial gaps remain in our understanding of interindividual variability in TCE metabolism and toxicity, especially in the liver. A hypothesis was tested that amounts of oxidative metabolites of TCE in mouse liver are associated with hepatic-specific toxicity. Oral dosing with TCE was conducted in subacute (600 mg/kg/d; 5 d; 7 inbred mouse strains) and subchronic (100 or 400 mg/kg/d; 1, 2, or 4 wk; 2 inbred mouse strains) designs. The quantitative relationship was evaluated between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P-450-mediated oxidation (trichloroacetic acid [TCA], dichloroacetic acid [DCA], and trichloroethanol) and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione] in serum and liver, and various hepatic toxicity phenotypes. In subacute study, interstrain variability in TCE metabolite amounts was observed in serum and liver. No marked induction of Cyp2e1 protein levels in liver was detected. Serum and hepatic levels of TCA and DCA were correlated with increased transcription of peroxisome proliferator-marker genes Cyp4a10 and Acox1 but not with degree of induction in hepatocellular proliferation. In subchronic study, serum and liver levels of oxidative metabolites gradually decreased over time despite continuous dosing. Hepatic protein levels of CYP2E1, ADH, and ALDH2 were unaffected by treatment with TCE. While the magnitude of induction of peroxisome proliferator-marker genes also declined, hepatocellular proliferation increased. This study offers a unique opportunity to provide a scientific data-driven rationale for some of the major assumptions in human health assessment of TCE.

  1. Comparative pulmonary toxicity assessment of pristine and functionalized multi-walled carbon nanotubes intratracheally instilled in rats: morphohistochemical evaluations.

    Science.gov (United States)

    Roda, E; Coccini, T; Acerbi, D; Barni, S; Vaccarone, R; Manzo, L

    2011-03-01

    Increasing interest in safety evaluation of carbon nanotubes (CNTs) has risen in relation to their wide applications, together with the evidence of their cytotoxic effects. It has been shown that chemical functionalization extends the applications of CNTs, conferring them new functions that cannot otherwise be acquired by pristine CNTs, but also impacts on biological response to CNTs, modifying their toxicological profile. We assessed the onset of pulmonary toxic effects caused by pristine MW-CNTs and functionalized MW-NH₂ or MW-COOH, 16 days after intratracheal instillation (1 mg/kg b.w.); major endpoints tested included (i) histopathology of lung (Haematoxylin/Eosin Staining), (ii) apoptotic/proliferating features examined by TUNEL and PCNA immunostaining, and (iii) presence/distribution of (1) Transforming Growth Factor-beta1 (TGFß1), (2) Interleukin-6 (IL-6) and (3) Collagen (Type I) investigated by immunochemical methods, as markers of lung toxicity, inflammation, and fibrosis, respectively. Lung histopathology from exposed animals showed dark, particulate-laden macrophages, reflecting carbon nanomaterial engulfing, both at alveolar and bronchiolar levels, after treatment with all the tested CNTs. Alteration of lung architecture was also observed in several areas showing collapsed thick-walled alveoli and the presence of micro-haemorrhagic foci. TUNEL and PCNA, indicative of apoptosis and cell proliferation respectively, showed a significant increase of immunopositive cells at bronchiolar, alveolar and macrophagic levels, as expression of an improved cellular turnover. Increased immunoreactivity for pulmonary TGFß1 and IL-6 was observed in treated rats, particularly in bronchiolar areas, collapsed alveoli and at stromal level, while evident changes for collagen were not detected. Taken together these findings demonstrated the general pulmonary toxicity coupled with inflammatory response after in vivo exposure to CNTs, without overt signs of fibrosis and

  2. Subclinical renal abnormalities in young thalassemia major and intermedia patients and its relation to chelation therapy

    Directory of Open Access Journals (Sweden)

    Amira A.M. Adly

    2014-10-01

    Conclusion: Subclinical renal affection can start earlier in TM patients compared to TI. Poor chelation is associated with early signs of renal affection. Periodic renal assessment of those patients is mandatory as they may be affected by hidden renal dysfunction.

  3. Comparative effectiveness of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers for major renal outcomes in patients with diabetes: A 15-year cohort study.

    Science.gov (United States)

    Wu, Hon-Yen; Peng, Chiao-Ling; Chen, Pei-Chun; Chiang, Chih-Kang; Chang, Chee-Jen; Huang, Jenq-Wen; Peng, Yu-Sen; Tu, Yu-Kang; Chu, Tzong-Shinn; Hung, Kuan-Yu; Chien, Kuo-Liong

    2017-01-01

    Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered to have similar renoprotective effects; so far there has been no consensus about their priorities. This study aimed to compare ACEIs and ARBs for major renal outcomes and survival in a 15-year cohort of adults with diabetes. This study utilized Taiwan's medical and pharmacy claims data in the Longitudinal Cohort of Diabetes Patients. The primary outcome was long-term dialysis, and secondary outcomes were hospitalization for acute kidney injury, hospitalization for hyperkalemia, all-cause death, cardiovascular death, and non-cardiovascular death. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes comparing ACEIs with ARBs. We conducted subgroup analyses and interaction tests among patients with different age and comorbid diseases. A total of 34,043 patients received ACEIs and 23,772 patients received ARBs. No differences were found for primary or secondary outcomes in the main analyses. ACEIs showed significantly lower hazard than ARBs for long-term dialysis among patients with cardiovascular disease (HR 0.80, 95% CI 0.66-0.97, interaction P = 0.003) or chronic kidney disease (0.81, 0.71-0.93, interaction P = 0.001). Our analyses show similar effects of ACEIs and ARBs in patients with diabetes. However, ACEIs might provide additional renoprotective effects among patients who have cardiovascular disease or chronic kidney disease.

  4. Long-term Cosmetic Outcomes and Toxicities of Proton Beam Therapy Compared With Photon-Based 3-Dimensional Conformal Accelerated Partial-Breast Irradiation: A Phase 1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Galland-Girodet, Sigolène; Pashtan, Itai; MacDonald, Shannon M.; Ancukiewicz, Marek [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Hirsch, Ariel E.; Kachnic, Lisa A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts (United States); Specht, Michelle; Gadd, Michele; Smith, Barbara L. [Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Powell, Simon N. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Taghian, Alphonse G., E-mail: ataghian@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-11-01

    Purpose: To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. Methods and Materials: From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. Results: At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Conclusions: Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity.

  5. Comparative study on toxicity of ZnO and TiO2 nanoparticles on Artemia salina: effect of pre-UV-A and visible light irradiation.

    Science.gov (United States)

    Bhuvaneshwari, M; Sagar, Bhawana; Doshi, Siddharth; Chandrasekaran, N; Mukherjee, Amitava

    2017-02-01

    This study evaluated the toxicity potential of ZnO and TiO2 nanoparticles under pre-UV-A irradiation and visible light condition on Artemia salina. The nanoparticle suspension was prepared in seawater medium and exposed under pre-UV-A (0.23 mW/cm(2)) and visible light (0.18 mW/cm(2)) conditions. The aggregation profiles of both nanoparticles (NPs) and dissolution of ZnO NPs under both irradiation conditions at various kinetic intervals (1, 24, 48 h) were studied. The 48-h LC50 values were found to be 27.62 and 71.63 mg/L for ZnO NPs and 117 and 120.9 mg/L for TiO2 NPs under pre-UV-A and visible light conditions. ZnO NPs were found to be more toxic to A. salina as compared to TiO2 NPs. The enhanced toxicity was observed under pre-UV-A-irradiated ZnO NPs, signifying its phototoxicity. Accumulation of ZnO and TiO2 NPs into A. salina depends on the concentration of particles and type irradiations. Elimination of accumulated nanoparticles was also evident under both irradiation conditions. Other than ZnO NPs, the dissolved Zn(2+) also had a significant effect on toxicity and accumulation in A. salina. Increased catalase (CAT) activity in A. salina indicates the generation of oxidative stress due to NP interaction. Thus, this study provides an understanding of the toxicity of photoreactive ZnO and TiO2 NPs as related to the effects of pre-UV-A and visible light irradiation.

  6. Evaluation of the efficacy and toxicity of protocol cisplatin, 5-fluorouracil, leucovorin compared to protocol fluorouracil, doxorubicin and mitomycin C in locally advanced and metastatic gastric cancer

    Directory of Open Access Journals (Sweden)

    Andrić Zoran

    2012-01-01

    Full Text Available Introduction. Still there is no consensus on the choice of the most efficient and the least toxic chemotherapy regimen in the treatment of advanced gastric cancer. Nowadays few therapy protocols are available for treating this disease. Objective. Study was conducted to compare the efficacy and toxicity of FAM (flurouracil, doxorubicin, mitomycin C with CDDP and FU/FA (cisplatin, 5-fluorouracil, leucovorin protocols in patients with locally advanced and metastatic gastric cancer. Methods. This randomized study involved a group of 50 patients with locally advanced or metastatic gastric cancer, who had not previously undergone chemotherapy treatment. Progression free survival, overall survival and drug toxicity were evaluated. For statistical analysis chi-square test, Kaplan-Meier curve and the log rank test were used. Results. The overall response rate was 20% in the group treated with FAM and 24% in the group treated with CDDP, FU/FA (4% of patients from each group had complete response, but without significant statistical difference. Median survival was 10.9 months in the FAM group and 11.8 months in CDDP, FU/FA group, with no statistically significant difference. Non-haematological and haematological toxicities of CDDP, FU/FA were considerably less frequent than of FAM, and there was no treatment related deaths in any of the groups. Conclusion. Both investigated regimens demonstrated moderate efficacy. The study shows in favour of justified application of both protocols, while in regard to toxicity CDDP and FU/FA can be recommended as preferable treatment for locally advanced and metastatic gastric cancer. New strategies should be considered for better efficacy in the treatment of advanced gastric cancer. New strategies are necessary with the goal to achieve a better therapeutic effect.

  7. Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Wortel, Ruud C.; Incrocci, Luca [Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; Heide, Uulke A. van der; Herk, Marcel van [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Heemsbergen, Wilma D., E-mail: w.heemsbergen@nki.nl [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands)

    2015-03-15

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.

  8. Comparative toxicity of physiological and biochemical parameters in Euglena gracilis to short-term exposure to potassium sorbate.

    Science.gov (United States)

    Engel, Fernanda; Pinto, Luciano Henrique; Del Ciampo, Lineu Fernando; Lorenzi, Luciano; Heyder, Carmen Diamantina Teixeira; Häder, Donat Peter; Erzinger, Gilmar Sidnei

    2015-01-01

    Potassium sorbate is the potassium salt of sorbic acid, is a widespread and efficient antioxidant that has multiple functions in plants, traditionally associated with the reactions of photosynthesis; however, it has moderate toxicity to various species including rat, fish, bacteria and human health. The effects of potassium sorbate on the movement and photosynthetic parameters of Euglena gracilis were studied during short-term exposure. Potassium sorbate showed acute toxicity to the green flagellate E. gracilis affecting different physiological parameters used as endpoints in an automatic bioassay such as motility, precision of gravitational orientation (r-value), upward movement and alignment, with mean EC50 values of 2867.2 mg L(-1). The concentrations above 625 mg L(-1) of potassium sorbate induce an inhibition of the photosynthetic efficiency and electron transport rate and, in concentrations more than 2500.0 mg L(-1), the Euglena cells undergo a complete inhibition of photosynthesis even at low light irradiation.

  9. Comparative evaluation of Jatropha curcas L. seed meals obtained by different methods of defatting on toxic, antinutritional and nutritive factors.

    Science.gov (United States)

    Xiao, Jianhui; Zhang, Hui

    2014-06-01

    Different methods of defatting have a great impact on toxic, antinutritional and nutritive factors in the oilseed meals. In order to find the most suitable methods of defatting for Jatropha curcas seed meals, the Jatropha curcas L. seed meals, defatted by Soxhlet extraction and screw-press were characterized for their toxic, anti-nutritional and nutrient factors in this study. The toxins (phorbolesters, 3.1 and 2.9 mg/g) and some anti-nutritional factors (saponins, 2.9 and 2.6%; phytates, 11.1 and 11.6%) in meals obtained by the two defatting methods were present at high concentrations. However, the trypsin inhibitors activity (TIA) and lectin (2.7 mg/g and 1.5 mg/ml) in the screw-pressed meal were significantly lower, due to the high temperature (120 °C) used in this defatting process. From nutritional side, the values of crude protein (CP), buffer-soluble nitrogen, non-protein nitrogen, pepsin insoluble nitrogen, in vitro protein digestibility (IVPD), as well as essential amino acid index (EAAI), biological value (BV), nutritional index (NI) and protein-digestibility-corrected amino acid score (PDCAAS) of the meal obtained by Soxhlet extraction were better than the screw-pressed meal. However, taking practical application into account, from detoxification side, screw-pressed meal is better for detoxification.

  10. Toxicity of terpenes on fibroblast cells compared to their hemolytic potential and increase in erythrocyte membrane fluidity.

    Science.gov (United States)

    Mendanha, Sebastião A; Moura, Soraia S; Anjos, Jorge L V; Valadares, Marize C; Alonso, Antonio

    2013-02-01

    Terpenes are considered potent skin permeation enhancers with low toxicity. Electron paramagnetic resonance (EPR) spectroscopy of the spin label 5-doxyl stearic acid (5-DSA) was used to monitor the effect of sesquiterpene nerolidol and various monoterpenes on membrane fluidity in erythrocyte and fibroblast cells. In addition, the hemolytic levels and cytotoxic effects on cultured fibroblast cells were also measured to investigate possible relationships between the cellular irritation potentials of terpenes and the ability to modify membrane fluidity. All terpenes increased cell membrane fluidity with no significant differences between the monoterpenes, but the effect of sesquiterpene was significantly greater than that of the monoterpenes. The IC(50) values for the terpenes in the cytotoxicity assay indicated that 1,8-cineole showed lower cytotoxicity and α-terpineol and nerolidol showed higher cytotoxicity. The correlation between the hemolytic effect and the IC(50) values for fibroblast viability was low (R=0.61); however, in both tests, nerolidol was among the most aggressive of terpenes and 1,8-cineole was among the least aggressive. Obtaining information concerning the toxicity and potency of terpenes could aid in the design of topical formulations optimized to facilitate drug absorption for the treatment of many skin diseases.

  11. Long-Term Effects of a Very Low Carbohydrate Compared With a High Carbohydrate Diet on Renal Function in Individuals With Type 2 Diabetes

    Science.gov (United States)

    Tay, Jeannie; Thompson, Campbell H.; Luscombe-Marsh, Natalie D.; Noakes, Manny; Buckley, Jonathan D.; Wittert, Gary A.; Brinkworth, Grant D.

    2015-01-01

    Abstract To compare the long-term effects of a very low carbohydrate, high-protein, low saturated fat (LC) diet with a traditional high unrefined carbohydrate, low-fat (HC) diet on markers of renal function in obese adults with type 2 diabetes (T2DM), but without overt kidney disease. One hundred fifteen adults (BMI 34.6 ± 4.3 kg/m2, age 58 ± 7 years, HbA1c 7.3 ± 1.1%, 56 ± 12 mmol/mol, serum creatinine (SCr) 69 ± 15 μmol/L, glomerular filtration rate estimated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFR 94 ± 12 mL/min/1.73 m2)) were randomized to consume either an LC (14% energy as carbohydrate [CHO diet combined with supervised exercise training (60 min, 3 day/wk) for 12 months. Body weight, blood pressure, and renal function assessed by eGFR, estimated creatinine clearance (Cockcroft–Gault, Salazar–Corcoran) and albumin excretion rate (AER), were measured pre- and post-intervention. Both groups achieved similar completion rates (LC 71%, HC 65%) and reductions in weight (mean [95% CI]; −9.3 [−10.6, −8.0] kg) and blood pressure (−6 [−9, −4]/−6[−8, −5] mmHg), P ≥ 0.18. Protein intake calculated from 24 hours urinary urea was higher in the LC than HC group (LC 120.1 ± 38.2 g/day, 1.3 g/kg/day; HC 95.8 ± 27.8 g/day, 1 g/kg/day), P diet effect. Changes in SCr (LC 3 [1, 5], HC 1 [−1, 3] μmol/L) and eGFR (LC −4 [−6, −2], HC −2 [−3, 0] mL/min/1.73 m2) did not differ between diets (P = 0.25). AER decreased independent of diet composition (LC −−2.4 [−6, 1.2], HC −1.8 [−5.4, 1.8] mg/24 h, P = 0.24); 6 participants (LC 3, HC 3) had moderately elevated AER at baseline (30–300 mg/24 h), which normalized in 4 participants (LC 2, HC 2) after 52 weeks. Compared with a traditional HC weight loss diet, consumption of an LC high protein diet does not adversely affect clinical markers of renal function in obese

  12. Toxicity of copper oxide nanoparticles in lung epithelial cells exposed at the air-liquid interface compared with in vivo assessment.

    Science.gov (United States)

    Jing, Xuefang; Park, Jae Hong; Peters, Thomas M; Thorne, Peter S

    2015-04-01

    The toxicity of spark-generated copper oxide nanoparticles (CuONPs) was evaluated in human bronchial epithelial cells (HBEC) and lung adenocarcinoma cells (A549 cells) using an in vitro air-liquid interface (ALI) exposure system. Dose-response results were compared to in vivo inhalation and instillation studies of CuONPs. Cells were exposed to filtered, particle-free clean air (controls) or spark-generated CuONPs. The number median diameter, geometric standard deviation and total number concentration of CuONPs were 9.2 nm, 1.48 and 2.27×10(7)particles/cm(3), respectively. Outcome measures included cell viability, cytotoxicity, oxidative stress and proinflammatory chemokine production. Exposure to clean air (2 or 4h) did not induce toxicity in HBEC or A549 cells. Compared with controls, CuONP exposures significantly reduced cell viability, increased lactate dehydrogenase (LDH) release and elevated levels of reactive oxygen species (ROS) and IL-8 in a dose-dependent manner. A549 cells were significantly more susceptible to CuONP effects than HBEC. Antioxidant treatment reduced CuONP-induced cytotoxicity. When dose was expressed per area of exposed epithelium there was good agreement of toxicity measures with murine in vivo studies. This demonstrates that in vitro ALI studies can provide meaningful data on nanotoxicity of metal oxides.

  13. Anemia and markers of erythropoiesis in pediatric kidney transplant recipients compared to children with chronic renal failure.

    Science.gov (United States)

    Krause, Irit; Davidovits, Miriam; Tamary, Hannah; Yutcis, Maria; Dagan, Amit

    2016-11-01

    PTA and anemia of CKD share a similar pathogenesis. However, PTA may be disproportionate to the reduction in the GFR. Data relating to the mechanism of PTA are scarce. We evaluated the erythropoiesis parameters in pediatric kidney recipients compared to children with CKD. A total of 100 patients (54 post-kidney TX, 46 with CKD) were enrolled in the single-center cohort study. GFR was found to be significantly lower in the CKD group (49.7±22.4 vs 72.9±28.5 mL/min/1.73 m², Panemia was significantly more common in the TX patients (52% vs 41.3%, PAnemia was significantly more common in the TX patients than in the CKD patients despite a better GFR. The higher prevalence of anemia in the TX group could not be explained by an iron deficiency or reduced EPO production. We speculate that immunosuppressive therapy together with resistance to EPO may play a role in the pathogenesis of post-transplantation anemia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all acknowle

  15. Renal fallure

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920705 Endothelin and acute renal failure:study on their relationship and possiblemechanisms. LIN Shanyan(林善锬), et al.Renal Res Lab, Huashan Hosp, Shanghai MedUniv, Shanghai, 200040. Natl Med J China 1992;72(4): 201-205. In order to investigate the role of endothelin

  16. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  17. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  18. Novel genes in renal aging

    NARCIS (Netherlands)

    Noordmans, Gerda Anke

    2015-01-01

    Renal aging is characterized by structural changes and functional decline. These changes make the elderly more vulnerable to chronic kidney disease, hypertension, and cardiovascular disease. Furthermore, they also make it more difficult to cope with stress factors, such as dehydration, toxicity, and

  19. Alterations in juvenile flatfish gill epithelia induced by sediment-bound toxicants: A comparative in situ and ex situ study.

    Science.gov (United States)

    Martins, Carla; Alves de Matos, António P; Costa, Maria H; Costa, Pedro M

    2015-12-01

    Juvenile Solea senegalensis were exposed in the laboratory (ex situ) and field (in situ) to different sediments of a moderately impacted estuary (the Sado, Portugal) for 28 days. A qualitative histopathological screening yielded scant lesions to gills, albeit alterations such as epithelial hyperplasia being evident and more frequent in fish exposed ex situ. Fully quantitative traits, namely chloride and goblet cell count and size revealed differences between the two bioassay approaches, with ex situ experiments likely enhancing bioavailability of toxicants. Chloride cells endured autolytic processes that could, at least in part, relate to contamination by mixed metals and polycyclic aromatic hydrocarbons (PAHs). Goblet cells did not reveal changes in the chemistry of mucous. Still, their number and size was reduced in fish exposed ex situ to the sediments most contaminated by PAHs, with evidence for adaptation. Also, copper histochemistry revealed the potential role of mucocytes in the regulation of metals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The Comparative Survey of Life Quality in Renal Transplant Recipients, Peritoneal Dialysis, and Hemodialysis Patients in Kerman in the Year 2013

    Directory of Open Access Journals (Sweden)

    Mehdi Amirkhani

    2014-06-01

    Conclusion: According to the results, the life quality of renal transplant recipients is better than other groups. Moreover, quality of life in hemodialysis patients was significantly lower than other groups.

  1. Carcinoembryonic antigen: assay following heat compared with perchloric acid extraction in patients with colon cancer, non-neoplastic gastrointestinal diseases, or chronic renal failure

    Energy Technology Data Exchange (ETDEWEB)

    Witherspoon, L.R.; Shuler, S.E.; Alyea, K.; Husserl, F.E.

    1983-10-01

    Heat inactivation has been proposed as an alternative to perchloric acid (PCA) precipitation for the extraction of carcinoembryonic antigen (CEA) from human plasma. A commercial RIA kit using heat inactivation was examined and results compared with those obtained with PCA precipitation. Adequate sensitivity (1.5 ..mu..g CEA/I plasma), satisfactory analytical recovery of CEA added to plasma, and dilutional linearity of samples found to have elevated CEA concentrations, were demonstrated for the heat-inactivation assay. Between-assay precision was better with the heat inactivation than with the PCA assay. Although the absolute concentration of CEA estimated after heat inactivation was consistently lower than that estimated after PCA extraction of plasma specimens, there was excellent correlation between results obtained with the two methods in colon cancer patients free of disease, colon cancer patients with residual or recurrent disease, patients with benign gastrointestinal disease, and in patients with chronic renal failure. The heat-inactivation assay is an excellent alternative to the PCA assay.

  2. Carcinoembryonic antigen: assay following heat compared with perchloric acid extraction in patients with colon cancer, non-neoplastic gastrointestinal diseases, or chronic renal failure.

    Science.gov (United States)

    Witherspoon, L R; Shuler, S E; Alyea, K; Husserl, F E

    1983-10-01

    Heat inactivation has been proposed as an alternative to perchloric acid (PCA) precipitation for the extraction of carcinoembryonic antigen (CEA) from human plasma. We examined a commercial RIA kit using heat inactivation, and compared results with those obtained with PCA precipitation. Adequate sensitivity (1.5 micrograms CEA/l plasma), satisfactory analytical recovery of CEA added to plasma, and dilutional linearity of samples found to have elevated CEA concentrations, were demonstrated for the heat-inactivation assay. Between-assay precision was better with the heat inactivation than with the PCA assay. Although the absolute concentration of CEA estimated after heat inactivation was consistently lower than that estimated after PCA extraction of plasma specimens, there was excellent correlation between results obtained with the two methods in colon cancer patients free of disease, colon cancer patients with residual or recurrent disease, patients with benign gastrointestinal disease, and in patients with chronic renal failure. We conclude that the heat-inactivation assay is an excellent alternative to the PCA assay.

  3. {sup 177}Lu-immunotherapy of experimental peritoneal carcinomatosis shows comparable effectiveness to {sup 213}Bi-immunotherapy, but causes toxicity not observed with {sup 213}Bi

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, Christof; Zoeckler, Christine; Beck, Roswitha; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Quintanilla-Martinez, Leticia [Universitaetsklinikum Tuebingen, Institute for Pathology, Tuebingen (Germany); Bruchertseifer, Frank [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2011-02-15

    {sup 213}Bi-d9MAb-immunoconjugates targeting gastric cancer cells have effectively cured peritoneal carcinomatosis in a nude mouse model following intraperitoneal injection. Because the {beta}-emitter {sup 177}Lu has proven to be beneficial in targeted therapy, {sup 177}Lu-d9MAb was investigated in this study in order to compare its therapeutic efficacy and toxicity with those of {sup 213}Bi-d9MAb. Nude mice were inoculated intraperitoneally with HSC45-M2 gastric cancer cells expressing d9-E-cadherin and were treated intraperitoneally 1 or 8 days later with different activities of specific {sup 177}Lu-d9MAb immunoconjugates targeting d9-E-cadherin or with nonspecific {sup 177}Lu-d8MAb. Therapeutic efficacy was evaluated by monitoring survival for up to 250 days. For evaluation of toxicity, both biodistribution of {sup 177}Lu-d9MAb and blood cell counts were determined at different time points and organs were examined histopathologically. Treatment with {sup 177}Lu-immunoconjugates (1.85, 7.4, 14.8 MBq) significantly prolonged survival. As expected, treatment on day 1 after tumour cell inoculation was more effective than treatment on day 8, and specific {sup 177}Lu-d9MAb conjugates were superior to nonspecific {sup 177}Lu-d8MAb. Treatment with 7.4 MBq of {sup 177}Lu-d9MAb was most successful, with 90% of the animals surviving longer than 250 days. However, treatment with therapeutically effective activities of {sup 177}Lu-d9MAb was not free of toxic side effects. In some animals lymphoblastic lymphoma, proliferative glomerulonephritis and hepatocarcinoma were seen but were not observed after treatment with {sup 213}Bi-d9MAb at comparable therapeutic efficacy. The therapeutic efficacy of {sup 177}Lu-d9MAb conjugates in peritoneal carcinomatosis is impaired by toxic side effects. Because previous therapy with {sup 213}Bi-d9MAb revealed comparable therapeutic efficacy without toxicity it should be preferred for the treatment of peritoneal carcinomatosis. (orig.)

  4. MR imaging findings of renal infarction induced by renal artery

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jun Woo; Kim, Suck; Kim, Yong Woo; Hu, Jin Sam; Choi, Sang Yoel; Moon, Tae Yong; Lee, Suck Hong; Kim, Byung Su; Lee, Chang Hun [Pusan National Univ., Pusan (Korea, Repulic of). Coll. of Medicine

    1998-02-01

    To assess the usefulness of diffusion-weighted imaging (DWI) in evaluating serial parenchymal changes in renal infarction induced by renal artery ligation, by comparing this with the conventional spin echo technique and correlating the results with the histopathological findings. In 22 rabbits, renal infarction was induced by ligation of the renal artery. Spin-echo T1-weighted imaging (T1WI), turbo spin-echo (TSE) T2-weighted imaging (T2WI), and DWI were performed, using a 1.5-T superconductive unit, at 30 minutes, 1 hour, 2,3,6, 12 and 24 hours, and 2, 3, 7 and 20 days after left renal artery ligation. Changes in signal intensity on T1WI, T2WI, and DWI were correlated with histopathologic findings. Diffusion-weighted imaging is useful for the detection of hyperacute renal infarction, and the apparent diffusion coefficient may provide additional information concerning its evolution. (author). 21 refs., 9 figs.

  5. Reduced Toxicity of Shiga Toxin (Stx Type 2c in Mice Compared to Stx2d Is Associated with Instability of Stx2c Holotoxin

    Directory of Open Access Journals (Sweden)

    Joshua C. Bunger

    2015-06-01

    Full Text Available Shiga toxin (Stx is an AB5 ribotoxin made by Stx-producing Escherichia coli (STEC. These organisms cause diarrhea, hemorrhagic colitis and the hemolytic uremic syndrome. STEC make two types of Stxs, Stx1 and/or Stx2. Stx2 has one prototype (a and six subtypes (b–g, but only STEC that make Stx2a, and/or Stx2c, or Stx2d are associated with severe disease. However, Stx2c is about 10-fold less toxic than Stx2d in vivo despite only two amino acid differences in the A subunit at positions 291 and 297. We made mutations at these two sites to create intermediate toxins between Stx2c and Stx2d, and determined the 50% cytotoxic dose on Vero cells before and after heat treatment, and the 50% lethal dose in mice of the toxins. We found that serine 291 was associated with increased toxicity in vivo and that either amino acid change from that in Stx2c to that in Stx2d increased heat stability. We also assessed the secondary structure of Stx2c and Stx2d by circular dichroism (CD spectroscopy. The CD studies suggest that Stx2c has a less-ordered secondary structure than Stx2d. We conclude that both amino acids at positions 291 and 297 in Stx2c contribute to its decreased stability and in vivo toxicity compared to Stx2d.

  6. Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies.

    Directory of Open Access Journals (Sweden)

    Daniel Y Heng

    Full Text Available The optimal sequencing of targeted therapies for metastatic renal cell carcinoma (mRCC is unknown. Observational studies with a variety of designs have reported differing results. The objective of this study is to systematically summarize and interpret the published real-world evidence comparing sequential treatment for mRCC.A search was conducted in Medline and Embase (2009-2013, and conference proceedings from American Society of Clinical Oncology (ASCO, ASCO Genitourinary Cancers Symposium (ASCO-GU, and European Society for Medical Oncology (ESMO (2011-2013. We systematically reviewed observational studies comparing second-line mRCC treatment with mammalian target of rapamycin inhibitors (mTORi versus vascular endothelial growth factor (VEGF tyrosine kinase inhibitors (TKI. Studies were evaluated for 1 use of a retrospective cohort design after initiation of second-line therapy, 2 adjustment for patient characteristics, and 3 use of data from multiple centers. Meta-analyses were conducted for comparisons of overall survival (OS and progression-free survival (PFS.Ten studies reported OS and exhibited significant heterogeneity in estimated second-line treatment effects (I2 = 68%; P = 0.001. Four of these were adjusted, multicenter, retrospective cohort studies, and these showed no evidence of heterogeneity (I2 = 0%; P = 0.61 and a significant association between second-line mTORi (>75% everolimus and longer OS compared to VEGF TKI (>60% sorafenib (HR = 0.82, 95% CI: 0.68 to 0.98 in a meta-analysis. Seven studies comparing PFS showed significant heterogeneity overall and among the adjusted, multicenter, retrospective cohort studies. Real-world observational data for axitinib outcomes was limited at the time of this study.Real-world studies employed different designs and reported heterogeneous results comparing the effectiveness of second-line mTORi and VEGF TKI in the treatment of mRCC. Within the subset of adjusted

  7. Laparoscopic Renal Cryoablation

    Science.gov (United States)

    Schiffman, Marc; Moshfegh, Amiel; Talenfeld, Adam; Del Pizzo, Joseph J.

    2014-01-01

    In light of evidence linking radical nephrectomy and consequent suboptimal renal function to adverse cardiovascular events and increased mortality, research into nephron-sparing techniques for renal masses widely expanded in the past two decades. The American Urological Association (AUA) guidelines now explicitly list partial nephrectomy as the standard of care for the management of T1a renal tumors. Because of the increasing utilization of cross-sectional imaging, up to 70% of newly detected renal masses are stage T1a, making them more amenable to minimally invasive nephron-sparing therapies including laparoscopic and robotic partial nephrectomy and ablative therapies. Cryosurgery has emerged as a leading option for renal ablation, and compared with surgical techniques it offers benefits in preserving renal function with fewer complications, shorter hospitalization times, and allows for quicker convalescence. A mature dataset exists at this time, with intermediate and long-term follow-up data available. Cryosurgical recommendations as a first-line therapy are made at this time in limited populations, including elderly patients, patients with multiple comorbidities, and those with a solitary kidney. As more data emerge on oncologic efficacy, and technical experience and the technology continue to improve, the application of this modality will likely be extended in future treatment guidelines. PMID:24596441

  8. Renal teratogens.

    Science.gov (United States)

    Morgan, Thomas M; Jones, Deborah P; Cooper, William O

    2014-09-01

    In utero exposure to certain drugs early in pregnancy may adversely affect nephrogenesis. Exposure to drugs later in pregnancy may affect the renin-angiotensin system, which could have an impact on fetal or neonatal renal function. Reduction in nephron number and renal function could have adverse consequences for the child several years later. Data are limited on the information needed to guide decisions for patients and providers regarding the use of certain drugs in pregnancy. The study of drug nephroteratogenicity has not been systematized, a large, standardized, global approach is needed to evaluate the renal risks of in utero drug exposures.

  9. Comparative toxicity of copper oxide bulk and nano particles in Nile Tilapia; Oreochromis niloticus: Biochemical and oxidative stress

    Directory of Open Access Journals (Sweden)

    Amr A. Abdel-Khalek

    2015-10-01

    Full Text Available Nile Tilapia; Oreochromis niloticus are commonly used in the assessment of aquatic environment quality and also considered as useful bio-indicators during environmental pollution monitoring. The LC50/96 h of copper oxide (bulk & nano particles [CuO (BPs & NPs] were 2205 & 150 mg/l, respectively. Two tested concentrations of CuO (BPs & NPs were selected: the first concentration was equivalent to (1/10 (220.5 & 15 mg/l, and the second was equivalent to (1/20 (110.25 & 7.5 mg/l LC50/96 h·CuO (BPs & NPs, respectively. While serum glucose, liver function tests (AST, ALT and ALP and kidney function tests (creatinine and uric acid showed a significant increase, serum total proteins, albumin, globulin and total lipids showed a significant decrease. Both liver and gill tissues of the studied fish showed a reduction in GSH content and an elevation in MDA and GPx activities. The present study also showed an elevation in liver CAT & SOD activities when exposed to both concentrations of CuO BPs and in the case of gills when exposed to both concentrations of CuO (BPs & NPs, although activity of these enzymes showed an inhibition in the liver when exposed to both concentrations of CuO NPs. The present study investigated whether CuO NPs are more toxic than CuO BPs.

  10. Clinical evaluation comparing the efficacy of aquacel Ag with vaseline gauze versus 1% silver sulfadiazine cream in toxic epidermal necrolysis.

    Science.gov (United States)

    Huang, Shu-Hung; Lin, Cen-Hung; Chang, Kao-Ping; Wu, Sheng-Hua; Lin, Sin-Daw; Lai, Chung-Sheng; Ou, Su-Fei; Lee, Su-Shin

    2014-05-01

    The purpose of this study was to determine whether using Aquacel Ag (ConvaTec, Skillman, New Jersey) with Vaseline (Unilever, London, England) gauze instead of silver sulfadiazine cream (SSD) as the wound care protocol to treat toxic epidermal necrolysis (TEN) can improve wound healing, pain control, and reduction of labor costs. A retrospective chart review. A burn center with 2 plastic surgeons and 11 nursing staff. A pathologist diagnosed TEN in 35 patients admitted to the burn center from 1995 to 2009. Parameters included the patient's profile, dressing choice, severity-of-illness score for TEN, time to 95% re-epithelialization, visual analog scale pain scores before second dressing change, and labor cost. The exclusion criterion was wound care with neither Aquacel Ag with Vaseline nor SSD exclusively. Twenty patients were enrolled in this study. In the group using Aquacel Ag with Vaseline gauze, the visual analog scale score was significantly less than that of the SSD group (P = .02). Labor costs were significantly lower in the Aquacel Ag with Vaseline gauze group (P < .01). Commencement of specific dressing to 95% re-epithelialization (P = .09) and time spent in the second dressing change (P = .05) had no statistical significance between the 2 groups. This study showed that Aquacel Ag with Vaseline gauze decreased pain and labor costs but did not shorten wound healing time. Thus, Aquacel Ag with Vaseline gauze can be an efficient method for treating TEN wounds.

  11. Comparative studies on plasma mineral status of cattle in fluoride toxic brackish water zone of Punjab, India

    Directory of Open Access Journals (Sweden)

    Sushma Chhabra

    2012-05-01

    Full Text Available Objective: Chronic fluoride intoxication or fluorosis is a worldwide health problem in humans and animals. The present research work was aimed to assess the status of copper, zinc, cobalt, manganese, magnesium, calcium and phosphorus in blood of fluorotic cattle in brackish water zone of Punjab. Methods: The present study was conducted in villages of district Muktsar, a brackish water zone, of Punjab state. Cattle (n=103 showing signs of dental lesions or lameness, from the villages with water fluoride concentration more than 1 ppm, were selected for the study whereas cattle (n=98 from villages with water fluoride concentration less than 1 ppm and with no clinical signs served as control. Blood samples were collected from both the groups and were analysed for minerals.Results: Significantly (P<0.05 higher plasma F concentrations were observed in animals of fluorotic region in comparison to healthy control animals. Concentrations of plasma Ca, Mg, Cu and Zn were significantly lower in cattle of hydrofluorotic region. Plasma phosphorus, iron and iodine concentrations were higher in animals of hydrofluorotic region whereas Mo and Mn did not differ between the two groups. Conclusions: Present study indicated decrease in certain essential minerals in animals of fluorotic region and such changes may contribute to the toxic effects associated with exposure to excess fluoride and salinity

  12. Sarcoidose renal

    Directory of Open Access Journals (Sweden)

    AQUINO MARIA ENEDINA CLAUDINO DE

    2001-01-01

    Full Text Available Em uma mulher de 62 anos, branca, em avaliação pré-operatória de facectomia, foram detectadas alterações urinárias, tendo sido firmados os diagnósticos de calculose renal esquerda e exclusão renal homolateral. No pré-operatório da nefrectomia foram evidenciados processo pulmonar intersticial bilateral e adenopatia torácica, cuja investigação foi adiada para após a cirurgia. No rim retirado foram detectados granulomas epitelióides não necrotizantes, o mesmo ocorrendo posteriormente em biópsia transbrônquica. A paciente foi tratada com metilprednisolona, com discreta melhora pulmonar, o que não ocorreu com a função renal. O diagnóstico final foi de sarcoidose com envolvimento pulmonar, ganglionar torácico e renal.

  13. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930150 Epidermal growth factor and its recep-tor in the renal tissue of patients with acute re-nal failure and normal persons.LIU Zhihong(刘志红),et al.Jinling Hosp,Nanjing,210002.Natl Med J China 1992;72(10):593-595.Epidermal growth factor(EGF)and its receptor(EGF-R)were identified by immunohis-tochemical method(4 layer PAP)in the renaltissue specimens obtained from 11 normal kid-neys and 17 cases of acute renal failure(ARF).The quantitative EGF and EGF-R in the tissuewere expressed as positive tubules per mm~2.The amount of EGF and EGF-R in renal tissue

  14. The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids: results from an open-label comparative study.

    Science.gov (United States)

    Mühlbacher, Ferdinand; Neumayer, Hans-Helmut; del Castillo, Domingo; Stefoni, Sergio; Zygmunt, Anthony J; Budde, Klemens

    2014-02-01

    This study evaluated the safety and efficacy of a sirolimus, corticosteroid, and cyclosporine reduction regimen in an open-label, 12-month trial of 420 de novo renal allograft recipients at 49 European transplant centers. One month post-transplantation, 357 patients were randomized to receive standard-dose cyclosporine (sCsA, n = 179) or reduced-dose cyclosporine (rCsA, n = 178). All patients also received sirolimus and corticosteroids. The primary end points were the rate of biopsy-confirmed acute rejection (BCAR) and renal function, as measured by serum creatinine. Baseline demographic and donor characteristics were similar between groups. BCAR rates at 12 months were not significantly different: 11.2% for rCsA patients and 16.2% for sCsA patients. Mean serum creatinine (±SEM) was significantly lower (1.75 ± 0.10 vs. 1.97 ± 0.07 mg/dl, P renal function in renal allograft recipients. Sirolimus administered with rCsA and corticosteroids provided adequate immunosuppression while reducing the potential for the nephrotoxic effects of cyclosporine. These findings may help to improve long-term renal allograft outcomes. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

  15. Is a Long Term Work in Automotive Industry a Risk Factor for Renal ...

    African Journals Online (AJOL)

    chronic renal failure can cause great disability or even death. ... Prevention of renal disorders is possible ... work with toxic metals and exposure to them is an important risk factor ..... The association between total urinary arsenic concentration.

  16. Metabolic activation of the olfactory toxicant, dichlobenil, in rat olfactory microsomes: comparative studies with p-nitrophenol.

    Science.gov (United States)

    Eriksson, C; Brittebo, E B

    1995-03-18

    The tissue-specific toxicity of the herbicide, dichlobenil (2,6-dichlorobenzonitrile), in the olfactory mucosa is related to a cytochrome P450 (P450)-dependent metabolism, depletion of glutathione and covalent binding of metabolites. Pretreatment of mice with diethyldithiocarbamate (DEDTC) protected against the dichlobenil-induced necrosis. Addition of DEDTC abolished the covalent binding of [14C]-dichlobenil to rat olfactory microsomes, whereas P4502E1-substrates such as ethanol, acetone or p-nitrophenol (NP) had no effect. The NP-hydroxylation in olfactory microsomes was > 6 times higher than that in liver microsomes and was markedly decreased following addition of dichlobenil, DEDTC or metyrapone. In liver microsomes of acetone-treated rats the NP-hydroxylation was markedly decreased following addition of DEDTC, whereas metyrapone and dichlobenil had no effect. In acetone-treated rats, the NP-hydroxylation and the metabolic activation of [14C]-dichlobenil in olfactory microsomes were decreased to 50 and 73% of untreated controls, respectively, whereas in liver microsomes these activities increased > 6 and 3.5-fold, respectively. An antibody to P4502E1 had no effect on the NP-hydroxylation or metabolic activation of [14C]-dichlobenil in olfactory microsomes, whereas the NP-hydroxylation in liver microsomes of acetone-treated rats was markedly decreased. In conclusion, the results do not support a major role for P4502E1 in the metabolic activation of dichlobenil or hydroxylation of NP in rat olfactory microsomes and suggest that these catalytic activities in the olfactory mucosa may represent a common form of P450.

  17. Comparative toxicity of a brominated flame retardant (tetrabromobisphenol A) on microalgae with single and multi-species bioassays.

    Science.gov (United States)

    Debenest, Timothée; Petit, Anne-Nöelle; Gagné, François; Kohli, Mohan; Nguyen, Nien; Blaise, Christian

    2011-09-01

    The potential threat of emerging chemicals to the aquatic flora is a major issue. The purpose of the study was to develop a multispecies microalgae test in order to determine the impact of species interactions on the cytoxicity of an emergent toxic contaminant: the tetrabromobisphenol A (TBBPA). Single and multi-species tests were thus performed to study the effects of this flame retardant on two microalgae (Pseudokirchneriella subcapitata and Nitzschia palea) commonly observed in freshwater. A synthetic medium was designed to allow the growth of both species. The algae were exposed to 1.8, 4.8, 9.2, 12.9 and 16.5 μM of TBBPA for 72 h. After staining with fluorescein diacetate (FDA), viable cells of each alga species were analyzed by flow cytometry based on chlorophyll autofluorescence and intracellular esterase activity. Density and abundance of viable cells were assessed to follow the population growth and the cell viability. In TBBPA treated samples, the growth of the two microalgae was significantly inhibited at the three highest concentrations (9.2, 12.9 and 16.5 μM) in the two tests. At the end of the experiment (t=72 h), the cell viability was also significantly smaller at these concentrations. The decreases of growth rate and viable cell abundance in TBBPA treated populations of N. palea were significantly higher in multi-species test in comparison with the single-species test. No significant differences were noticed between the two tests for P. subcapitata populations exposed to TBBPA. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  18. Comparison of the renal disease at the Tibetan plateaus and plain based on renal biopsy data

    Institute of Scientific and Technical Information of China (English)

    周岩

    2014-01-01

    Objective To compare the characteristics of renal disease based on renal biopsy data between the Tibetan plateaus and the plain.Methods 160 chronic kidney diseases patients underwent renal biopsy from the plain and80 cases from Tibet plateau were compared in a parallel controlled manner.The relationship of renal pathology and clinical signs were also compared.Results(1)The male to female ratio was quite different between Tibet

  19. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005234 Association between serum fetuin-A and clinical outcome in end-stage renal disease patients. WANG Kai(王开), Dept Renal Dis, Renji Hosp Shanghai, 2nd Med Univ, Shanghai 200001. Chin J Nephrol, 2005;21(2):72-75. Objective: To investigate the change of serum fetuin-A level before and after dialysis, and the association of serum fetuin-A level with clinical parameters

  20. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950351 Serum erythropoietin levels in chronic renalinsufficiency.ZHAI Depei(翟德佩),et al.DeptNephrol.General Hosp,Tianjin Med Univ,Tianjin,300000.Tianjin Med J 1995;23(1):19-21.Patients with chronic renal insufficiency(CRI) areoften associated with anemia.The deficiency of EPOproduction in the kidney is thought to be a key factorin the pathogenesis of renal anemia.Serum erythropoi-

  1. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

  2. Renal Hemangiopericytoma

    Directory of Open Access Journals (Sweden)

    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  3. Renal elimination of organic anions in cholestasis

    Institute of Scientific and Technical Information of China (English)

    Adriana Mónica Tortes

    2008-01-01

    The disposition of most drugs is highly dependent on specialized transporters.OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells,identified as contributors to xenobiotic and endogenous organic anion secretion.It is well known that cholestasis may cause renal damage.Impairment of kidney function produces modifications in the renal elimination of drugs.Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis.Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters.The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.

  4. Potential molecular therapy for acute renal failure.

    Science.gov (United States)

    Humes, H D

    1993-01-01

    Ischemic and toxic acute renal failure is reversible, due to the ability of renal tubule cells to regenerate and differentiate into a fully functional lining epithelium. Recent data support the thesis that recruitment or activation of macrophages to the area of injury results in local release of growth factors to promote regenerative repair. Because of intrinsic delay in the recruitment of inflammatory cells, the exogenous administration of growth promoters early in the repair phase of acute renal failure enhances renal tubule cell regeneration and accelerates renal functional recovery in animal models of acute renal failure. Molecular therapy for the acceleration of tissue repair in this disease process may be developed in the near future.

  5. Renal failure in patients with multiple myeloma.

    Science.gov (United States)

    Almueilo, Samir H

    2015-01-01

    Renal dysfunction is encountered in 20-25% of patients with multiple myeloma (MM) at the time of diagnosis. There is often a precipitating event. Several biochemical and clinical correlations with renal failure in MM have been reported. Renal failure in MM is associated with worse outcome of the disease. We retrospectively analyzed the medical records of 64 patients with MM admitted to our institution during the period January 1992 to December 2012. Abnormal renal function was observed in 24 (37.5%) patients and 17 (26.6%) of them had renal failure; 14 of the 17 (82.4%) of patients with renal failure had Stage III MM. Urine Bence- Jones protein was positive in ten (58.8%) patients with renal failure versus ten (21.3%) patients without renal failure (P = 0.004). Potential precipitating factors of renal failure were determined in nine patients. Renal function normalized in 11 patients with simple measures, while six patients required hemodialysis; one remained dialysis dependent till time of death. Early mortality occurred in five (29.4%) patients with renal failure as compared with two (4.3%) patients in the group without renal failure (P = 0.005). In conclusion, renal failure is associated with a higher tumor burden and Bence-Jones proteinuria in patients with MM. It is reversible in the majority of patients; however, early mortality tends to be higher in patients with persistent renal failure.

  6. Cytotoxicity of Spent Pot Liner on Allium cepa root tip cells: A comparative analysis in meristematic cell type on toxicity bioassays.

    Science.gov (United States)

    Palmieri, Marcel José; Andrade-Vieira, Larissa Fonseca; Campos, José Marcello Salabert; Dos Santos Gedraite, Leonardo; Davide, Lisete Chamma

    2016-11-01

    Spent Pot Liner (SPL) is a waste generated during the production of aluminum. It is comprised of a mixture of substances most of which, like cyanide, aluminum and fluoride, are toxic. Previous studies indicate the highly toxic nature of SPL. However studies using cells of the differentiation/elongation zone of the root meristem (referred as M2 cells in this study) after a proper recovery period in water were never considered. Using these cells could be useful to further understanding the toxicity mechanisms of SPL. A comparative approach between the effects on M2 cells and meristematic cells of the proximal meristem zone (referred as M1 cells in this study) could lead to understanding how DNA damage caused by SPL behaves on successive generations of cells. Allium cepa cells were exposed to 4 different concentrations of SPL (2.5, 5, 7.5 and 10gL(-1)) mixed with soil and diluted in a CaCl2 0.01M to simulate the ionic forces naturally encountered on the environment. A solution containing only soil diluted on CaCl2 0.01M was used as control. M1 and M2 cells were evaluated separately, taking into account four different parameters: (1) mitotic alterations (MA); (2) presence of condensed nuclei (CN); (3) mitotic index (MI); (4) presence of micronucleus (MCN). Significant differences were observed between M1 and M2 roots tip cells for these four parameters accessed. M1 cells was more prompt to reveal citogenotoxicity through the higher frequency of MA observed. Meanwhile, for M2 cells higher frequencies of MCN and CN was noticed, followed by a reduction of MI. Also, it was possible to detect significant differences between the tested treatments and the control on every case. These results indicate SPL toxic effects carries on to future cells generations. This emphasizes the need to properly manage this waste. Joint evaluation of cells from both M1 and M2 regions was proven valuable for the evaluation of a series of parameters on all toxicity tests.

  7. 3种雷公藤制剂对大鼠急性毒性损伤的比较%Comparative Study on Rat Acute Toxicity of Three Tripterygium Wilfordii Preparations

    Institute of Scientific and Technical Information of China (English)

    王楠楠; 王爱武; 林晓燕

    2012-01-01

    Objective To observe and compare the acute toxicity of three Tripterygium Wilfordii Preparations. Methods The rats were randomly divided into 4 groups, the control group, Tripterygium wilfordii tablet group, Tripterygium glycosides tablet group, Tripterygium hypoghucum Hutch group. Rats were given corresponding drugs. General symptom and organs were observed, and AST, ALT, BUN in serum were measured. Liver and renal histology was examined by HE staining. Results The AST of Tripterygium wilfordii tablet group and Tripterygium glycosides tablet group, the ALT of Tripterygium glycosides tablet group were higher than those of the control group(P 0.05) between medication groups in AST/ALT and BUN. The degree of Tripterygium hypoghucum Hutch group changes was less than that of two other medication groups. Conclusion The three Tripterygium Wilfordii Preparations can induce the renal and liver acute lesion, and the toxicity of the Tripterygium wilfordii tablet and Tripterygium glycosides tablet is more serious than that of Tripterygium hypoglaucum Hutch.%目的 观察并比较临床常用3种雷公藤制剂对大鼠的急性毒性.方法 将Wistar大鼠随机分为对照组、雷公藤片组、雷公藤多苷片组、昆明山海棠片组,各组分别灌胃给予相应的人日用量60倍药物,观察一般症状,检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、血清尿素氮(BUN)值,肉眼观察心、肝、脾、肺及肾的组织形态并计算脏器指数.对肝肾进行HE染色,观察并比较各组的病理损伤程度.结果 与对照组相比,雷公藤片组、雷公藤多苷片组AST值显著升高(P<0.05),雷公藤多苷片组ALT值显著升高(P<0.05),各给药组AST/ALT、BUN变化均不显著(P>0.05);各给药组肝、肾组织均出现一定程度病理损伤,其中肾组织损伤更严重,给药组间比较,昆明山海棠片肝肾损伤轻于另外两组.结论 3种雷公藤制剂一次性大剂量给予大鼠均出现不同程度的急性

  8. Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Sakellari, Ioanna; Mallouri, Despina; Gavriilaki, Eleni; Batsis, Ioannis; Kaliou, Maria; Constantinou, Varnavas; Papalexandri, Apostolia; Lalayanni, Chrysavgi; Vadikolia, Chrysanthi; Athanasiadou, Anastasia; Yannaki, Evangelia; Sotiropoulos, Damianos; Smias, Christos; Anagnostopoulos, Achilles

    2017-03-01

    Treosulfan has been incorporated in conditioning regimens for sustained remission without substantial toxicity and treatment-related mortality (TRM). We aimed to analyze the safety and efficacy of a fludarabine 150 mg/m(2) and treosulfan 42 g/m(2) (FluTreo) conditioning regimen in medically infirm patients. Outcomes were compared with those of a similar historical group treated with fludarabine 150 mg/m(2) to 180 mg/m(2), busulfan 6.4 mg/kg, and antithymocyte globulin (ATG) 5 mg/kg to 7.5 mg/kg (FluBuATG). Thirty-one consecutive patients with acute myeloid leukemia (AML; n = 21), myelodysplastic syndrome (MDS; n = 6), or treatment-related AML (n = 4) received FluTreo conditioning. The historical group consisted of 26 consecutive patients treated with FluBuATG. In the FluTreo group, engraftment was prompt in all patients and 74% achieved >99% donor chimerism by day +30. No grades III or IV organ toxicities were noted. One-year cumulative incidences (CI) of acute and chronic graft-versus-host disease (GVHD) were 19.4% and 58.4%. The groups were similar for age, disease risk, lines of treatment, hematopoietic cell transplantation-specific comorbidity index, and acute or chronic GVHD incidence, except that there were more matched unrelated donor recipients in the FluTreo group (P < .001). With 20 (range, 2 to 36) months follow-up for FluTreo and 14 (range, 2 to 136) for FluBuATG, the 1-year cumulative overall survival (OS) probability was 76% versus 57%, respectively (P = .026); 1-year disease-free survival (DFS) was 79% versus 38% (P < .001). In multivariate analysis, the only significantly favorable factor for OS and DFS was FluTreo (P = .010 and P = .012). The CI of relapse mortality was markedly decreased in FluTreo versus FluBuATG (7.4% versus 42.3%, P < .001). In conclusion, the treosulfan-based regimen resulted in favorable OS and DFS with acceptable toxicity and low relapse rates compared with busulfan-based conditioning.

  9. Comparative effectiveness of adrenal sparing radical nephrectomy and non-adrenal sparing radical nephrectomy in clear cell renal cell carcinoma: Observational study of survival outcomes

    Science.gov (United States)

    Nason, Gregory J.; Walsh, Leon G.; Redmond, Ciaran E.; Kelly, Niall P.; McGuire, Barry B.; Sharma, Vidit; Kelly, Michael E.; Galvin, David J.; Mulvin, David W.; Lennon, Gerald M.; Quinlan, David M.; Flood, Hugh D.; Giri, Subhasis K.

    2015-01-01

    Introduction: We compare the survival outcomes of patients with clear cell renal cell carcinoma (RCC) treated with adrenal sparing radical nephrectomy (ASRN) and non-adrenal sparing radical nephrectomy (NASRN). Methods: We conducted an observational study based on a composite patient population from two university teaching hospitals who underwent RN for RCC between January 2000 and December 2012. Only patients with pathologically confirmed RCC were included. We excluded patients undergoing cytoreductive nephrectomy, with loco-regional lymph node involvement. In total, 579 patients (ASRN = 380 and NASRN = 199) met our study criteria. Patients were categorized by risk groups (all stage, early stage and locally advanced RCC). Overall survival (OS) and cancer-specific survival (CSS) were analyzed for risk groups. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards regression. Results: The median follow-up was 41 months (range: 12–157). There were significant benefits in OS (ASRN 79.5% vs. NASRN 63.3%; p = 0.001) and CSS (84.3% vs. 74.9%; p = 0.001), with any differences favouring ASRN in all stage. On multivariate analysis, there was a trend towards worse OS (hazard ratio [HR] 1.759, 95% confidence interval [CI] 0.943–2.309, p = 0.089) and CSS (HR 1.797, 95% CI 0.967–3.337, p = 0.064) in patients with NASRN (although not statistically significant). Of these patients, only 11 (1.9%) had adrenal involvement. Conclusions: The inherent limitations in our study include the impracticality of conducting a prospective randomized trial in this scenario. Our observational study with a 13-year follow-up suggests ASRN leads to better survival than NASRN. ASRN should be considered the gold standard in treating patients with RCC, unless it is contraindicated. PMID:26425218

  10. A randomized trial with steroids and antithymocyte globulins comparing cyclosporine/azathioprine versus tacrolimus/mycophenolate mofetil (CATM2) in renal transplantation.

    Science.gov (United States)

    Vacher-Coponat, Henri; Moal, Valerie; Indreies, Monica; Purgus, Raj; Loundou, Anderson; Burtey, Stephane; Brunet, Philippe; Moussi-Frances, Julie; Daniel, Laurent; Dussol, Bertrand; Berland, Yvon

    2012-02-27

    The best immunosuppressive regimen in benefit-risk ratio in renal transplantation is debated. Nowadays, tacrolimus (Tac) and mycophenolate mofetil (MMF) are considered more efficient than cyclosporine A (CsA) and MMF, but recent studies have challenged this assumption. We conducted a monocentric, prospective, open-labeled, randomized, and controlled trial comparing CsA/azathioprine (Aza) versus Tac/MMF in 289 kidney transplant recipients treated with antithymocyte globulins and prednisone. Primary outcome was the number of patients with clinically suspected acute rejection at 1 year. Secondary outcomes were the number of patients with biopsy-proven acute rejection (BPAR), estimated glomerular filtration rate (eGFR), patient and graft survivals, and adverse events at 1 and 3 years. During the first year, 21 patients had clinically suspected acute rejection with CsA/Aza (14.4%) vs. 11 (7.7%) with Tac/MMF (P=0.07). BPAR, including borderline, was more frequent in the CsA/Aza group (14.4%) than in the Tac/MMF group (5.6%; P=0.013). At 1 year, patient and graft survivals were not different, and eGFR was 48±1 in the CsA/Aza group and 53±1 mL/min/1.73 m in the Tac/MMF group (P=0.007). There was no significant difference in diabetes after transplantation (16.8% and 18.8%, respectively). With antithymocyte globulins and steroids, clinically suspected acute rejections did not differ between CsA/Aza and Tac/MMF arms. Analysis of secondary endpoints showed a lower rate of BPAR, including border line, and a higher eGFR in the Tac/MMF group. CsA/Aza allowed a low acute rejection rate, but Tac/MMF seemed as a better regimen regarding severe secondary outcomes.

  11. A STUDY ON LIMITATION OF HIGH-ENERGY SHOCK WAVE-INDUCED RENAL DAMAGE BY SALVIA MILTIORRHIZAE INJECTION IN RABBIT MODEL

    Institute of Scientific and Technical Information of China (English)

    陈兴发; 盛斌武; 贺大林

    2004-01-01

    Objective To study the protective function of Salvia Miltiorrhizae on high-energy shockwaves (HESW) induced renal damage. Methods Thirty healthy New Zealand adult male white rabbits were randomly divided into Salvia Miltiorrhizae group and control group with 15 in each. Three days before extracorpeal shock wave lithotripsy (ESWL) the two groups were injected Salvia Miltiorrhizae and physiological saline respectively. Plasma endothelin-1 (ET-1), Superoxide dismutase (SOD) and malondialdehyde (MDA) were determined and renal morphology was observed. Results After ESWL, levels of ET-1 and MDA increased significantly, the activity of SOD decreased significantly compared with those before ESWL in control group (P0.05). After shocking, SOD, related to renal protection, in Salvia Miltiorrhizae group was significantly higher than that of controls (P<0.05). Renal morphological injury was slight in Salvia Miltiorrhizae group. Conclusion Salvia Miltiorrhizae injection has protective function on renal toxicity induced by high-energy shock waves.

  12. Systematic review of vismodegib toxicity profile in the treatment of advanced basal cell carcinomas compared to other systemic therapies in dermatology.

    Science.gov (United States)

    Juhasz, Margit L W; Marmur, Ellen S

    2014-06-01

    Vismodegib is a first-in-class, hedgehog-signal inhibitor that is FDA-approved for use with advanced basal cell carcinomas (BCCs) that cannot be removed by either surgical resection or treated with radiation. Release of the drug was fast-tracked because of need for this type of drug, and its overall efficacy in clinical trial by producing either regression or even resolution of advanced BCCs. Compared to placebo, patients using vismodegib have arrested BCC progression, reduced size of BCC, and decreased recurrence of BCC. Unfortunately, vismodegib has notable adverse effects (especially those of alopecia, gastrointestinal, muscle spasms, and dysguesia) that make dermatologists reluctant to prescribe the drug and patients unwilling to undergo therapy. In this article, we tackle this dilemma by comparing the toxicity profile of vismodegib to the adverse effect profiles of other dermatologic chemotherapeutics, immunomodulators, retinoids, and biologics. Considering that many of these drugs carry their own risks and those drugs used to treat advanced melanoma have similar toxicity profiles to that of vismodegib, we hope dermatologists and patients alike will be more willing to try vismodegib as a treatment option for advanced BCCs in the future.

  13. [Cyclosporin, toxicity and efficacy in rejection of liver allografts in the rat].

    Science.gov (United States)

    Settaf, A; Gugenheim, J; Lahlou, M K; Gigou, M; Capron-Laudereau, M; Charpentier, B; Reynes, M; Lokiec, F; Bismuth, H

    1989-01-01

    52 orthotopic liver transplants were performed in DA to lewis rat strain combination, in order to appreciate cyclosporine toxicity, and efficacy at doses of 10 mg/kg day (G II) and 20 mg/kg/day (GIII) compared to liver allografts in DA/lewis rats. The first signs of cyclosporine hepatotoxicity are biological (increased plasma level of bilirubine and transaminase) that were noticed at the dose of 20 mg/kg/day. Histological signs (cells inclusion, hepatocytic necrosis) appeared late and were less constant as well as difficult to assert creatinine plasma level was the best reflect of cyclosporine nephrotoxicity. Renal toxicity was practically constant at the dose of 20 mg/kg/day. In spite of renal and hepatic toxicity, cyclosporin by itself, allows the abolition of the acute rejection of liver allografts in the rat.

  14. Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation.

    Science.gov (United States)

    Ahmad, Shiekh Tanveer; Arjumand, Wani; Nafees, Sana; Seth, Amlesh; Ali, Nemat; Rashid, Summya; Sultana, Sarwat

    2012-01-25

    Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The present study demonstrates the comparative hepatoprotective and nephroprotective activity of hesperidin (HD), a naturally occurring bioflavonoid against APAP induced toxicity. APAP induces hepatotoxicity and nephrotoxicity as was evident by abnormal deviation in the levels of antioxidant enzymes. Moreover, APAP induced renal damage by inducing apoptotic death and inflammation in renal tubular cells, manifested by an increase in the expression of caspase-3, caspase-9, NFkB, iNOS, Kim-1 and decrease in Bcl-2 expression. These results were further supported by the histopathological examination of kidney. All these features of APAP toxicity were reversed by the co-administration of HD. Therefore, our study favors the view that HD may be a useful modulator in alleviating APAP induced oxidative stress and toxicity.

  15. Comparative venom gland transcriptome analysis of the scorpion Lychas mucronatus reveals intraspecific toxic gene diversity and new venomous components.

    Science.gov (United States)

    Ruiming, Zhao; Yibao, Ma; Yawen, He; Zhiyong, Di; Yingliang, Wu; Zhijian, Cao; Wenxin, Li

    2010-07-28

    Lychas mucronatus is one scorpion species widely distributed in Southeast Asia and southern China. Anything is hardly known about its venom components, despite the fact that it can often cause human accidents. In this work, we performed a venomous gland transcriptome analysis by constructing and screening the venom gland cDNA library of the scorpion Lychas mucronatus from Yunnan province and compared it with the previous results of Hainan-sourced Lychas mucronatus. A total of sixteen known types of venom peptides and proteins are obtained from the venom gland cDNA library of Yunnan-sourced Lychas mucronatus, which greatly increase the number of currently reported scorpion venom peptides. Interestingly, we also identified nineteen atypical types of venom molecules seldom reported in scorpion species. Surprisingly, the comparative transcriptome analysis of Yunnan-sourced Lychas mucronatus and Hainan-sourced Lychas mucronatus indicated that enormous diversity and vastly abundant difference could be found in venom peptides and proteins between populations of the scorpion Lychas mucronatus from different geographical regions. This work characterizes a large number of venom molecules never identified in scorpion species. This result provides a comparative analysis of venom transcriptomes of the scorpion Lychas mucronatus from different geographical regions, which thoroughly reveals the fact that the venom peptides and proteins of the same scorpion species from different geographical regions are highly diversified and scorpion evolves to adapt a new environment by altering the primary structure and abundance of venom peptides and proteins.

  16. Comparative venom gland transcriptome analysis of the scorpion Lychas mucronatus reveals intraspecific toxic gene diversity and new venomous components

    Directory of Open Access Journals (Sweden)

    Zhijian Cao

    2010-07-01

    Full Text Available Abstract Background Lychas mucronatus is one scorpion species widely distributed in Southeast Asia and southern China. Anything is hardly known about its venom components, despite the fact that it can often cause human accidents. In this work, we performed a venomous gland transcriptome analysis by constructing and screening the venom gland cDNA library of the scorpion Lychas mucronatus from Yunnan province and compared it with the previous results of Hainan-sourced Lychas mucronatus. Results A total of sixteen known types of venom peptides and proteins are obtained from the venom gland cDNA library of Yunnan-sourced Lychas mucronatus, which greatly increase the number of currently reported scorpion venom peptides. Interestingly, we also identified nineteen atypical types of venom molecules seldom reported in scorpion species. Surprisingly, the comparative transcriptome analysis of Yunnan-sourced Lychas mucronatus and Hainan-sourced Lychas mucronatus indicated that enormous diversity and vastly abundant difference could be found in venom peptides and proteins between populations of the scorpion Lychas mucronatus from different geographical regions. Conclusions This work characterizes a large number of venom molecules never identified in scorpion species. This result provides a comparative analysis of venom transcriptomes of the scorpion Lychas mucronatus from different geographical regions, which thoroughly reveals the fact that the venom peptides and proteins of the same scorpion species from different geographical regions are highly diversified and scorpion evolves to adapt a new environment by altering the primary structure and abundance of venom peptides and proteins.

  17. Acitretin treatment of premalignant and malignant skin disorders in renal transplant recipients: clinical effects of a randomized trial comparing two doses of acitretin.

    NARCIS (Netherlands)

    Sevaux, R.G.L. de; Smit, J.V.; Jong, E.M.G.J. de; Kerkhof, P.C.M. van de; Hoitsma, A.J.

    2003-01-01

    INTRODUCTION: After renal transplantation, the incidence of premalignant and malignant skin lesions is high. Treatment with acitretin improves the number and aspect of actinic keratoses and appears to reduce the incidence of squamous cell carcinomas, but treatment is hampered by frequent side effect

  18. FISIOPATOLOGÍA DE LA INSUFICIENCIA RENAL AGUDA POR CISPLATINO

    Directory of Open Access Journals (Sweden)

    Rodriguez Macías EL

    2013-09-01

    Full Text Available Cisplatin is one of the major antineoplastic used for treatment of tumors such as testicular, ovarian, cervical, lung, bladder and head, among others. It has been described various types of toxicities induced by cisplatin, but the renal is the main one. This toxicity consist sof an acute reduction in renal plasma flow and a decline in glomerular filtration and installation of a tubular necrosis, with predominant involvement of the distal tubules and accumulation of cellular debris (lumen obstruction. Other mechanisms involved in renal injury are microangiopathy and pro-inflammatory mediators. We conclude that the nephrotoxicity caused by cisplatin can induce renal failure in which tubular structural damage predominates.

  19. How renal cells handle urea.

    Science.gov (United States)

    Bagnasco, S M

    2000-01-01

    The urine concentration process requires an osmolality gradient along the renal cortico-medullary axis, with highest values in the renal papilla. NaCl and urea are the major solutes in the renal inner medulla, concentrations of urea up to 500-600 mM are found in the rat renal papilla. Urea can diffuse across cell membranes and contributes to balance intracellular and extracellular osmotic equilibrium. However, urea has perturbing effects on enzyme activity, and in concentrations above 300 mM is toxic for renal cultured cells. There is increasing evidence that urea can induce cellular responses distinct from those due to NaCl and other non-permeable solutes, including upregulation of immediate-early genes (IEGs). Urea transport by epithelial and endothelial cells is important for intra-medullary urea recycling and preservation of high urea concentration in the inner medulla. Trans-cellular movement of urea in cells expressing urea transporters may influence intracellular levels of this solute and modulate urea-induced signaling pathways. Regulation of urea transporters expression and activity can therefore be viewed as one aspect of cellular adaptation to urea. We have identified tonicity-responsive transcription as one mechanism regulating expression of the urea transporter UT-A. The short-term and long-term effects of variable extracellular urea concentration on the function of renal cells remain still unclear.

  20. Toxicity assessment due to sub-chronic exposure to individual and mixtures of four toxic heavy metals

    Energy Technology Data Exchange (ETDEWEB)

    Cobbina, Samuel J.; Chen, Yao [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Zhou, Zhaoxiang; Wu, Xueshan; Zhao, Ting [School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013 (China); Zhang, Zhen [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Feng, Weiwei; Wang, Wei [School of Food and Biological Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Li, Qian [School of Pharmacy, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Wu, Xiangyang, E-mail: wuxy@ujs.edu.cn [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Yang, Liuqing, E-mail: yangliuqing@ujs.edu.cn [School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013 (China)

    2015-08-30

    Highlights: • Low dose single and mixtures of toxic metals had adverse effect on mice. • Metal mixtures exhibited higher toxicities compared to individual metals. • Mixtures of low dose Pb + Hg + Cd induced neuronal degeneration in brain of mice. • Exposure to Pb + Hg + As + Cd showed renal tubular necrosis in kidney. - Abstract: Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on toxicity of low dose mixtures. In this study, lead (Pb) (0.01 mg/L), mercury (Hg) (0.001 mg/L), cadmium (Cd) (0.005 mg/L) and arsenic (As) (0.01 mg/L) were administered individually and as mixtures to 10 groups of 40 three-week old mice (20 males and 20 females), for 120 days. The study established that low dose exposures induced toxicity to the brain, liver, and kidney of mice. Metal mixtures showed higher toxicities compared to individual metals, as exposure to low dose Pb + Hg + Cd reduced brain weight and induced structural lesions, such as neuronal degeneration in 30-days. Pb + Hg + Cd and Pb + Hg + As + Cd exposure induced hepatocellular injury to mice evidenced by decreased antioxidant activities with marginal increases in MDA. These were accentuated by increases in ALT, AST and ALP. Interactions in metal mixtures were basically synergistic in nature and exposure to Pb + Hg + As + Cd induced renal tubular necrosis in kidneys of mice. This study underlines the importance of elucidating the toxicity of low dose metal mixtures so as to protect public health.

  1. The contrast-enhanced Doppler ultrasound with perfluorocarbon exposed sonicated albumin does not improve the diagnosis of renal artery stenosis compared with angiography

    Directory of Open Access Journals (Sweden)

    Bortolotto Luiz A

    2004-09-01

    Full Text Available Abstract There are no studies investigating the effect of the contrast infusion on the sensitivity and specificity of the main Doppler criteria of renal artery stenosis (RAS. Our aim was to evaluate the accuracy of these Doppler criteria prior to and following the intravenous administration of perfluorocarbon exposed sonicated albumin (PESDA in patients suspected of having RAS. Thirty consecutive hypertensive patients (13 males, mean age of 57 ± 10 years suspected of having RAS by clinical clues, were submitted to ultrasonography (US of renal arteries before and after enhancement using continuous infusion of PESDA. All patients underwent angiography, and haemodynamically significant RAS was considered when ≥50%. At angiography, it was detected RAS ≥50% in 18 patients, 5 with bilateral stenosis. After contrast, the examination time was slightly reduced by approximately 20%. In non-enhanced US the sensitivity was better when based on resistance index (82.9% while the specificity was better when based on renal aortic ratio (89.2%. The predictive positive value was stable for all indexes (74.0%–88.0% while negative predictive value was low (44%–51%. The specificity and positive predictive value based on renal aortic ratio increased after PESDA injection respectively, from 89 to 97.3% and from 88 to 95%. In hypertensives suspected to have RAS the sensitivity and specificity of Duplex US is dependent of the criterion evaluated. Enhancement with continuous infusion of PESDA improves only the specificity based on renal aortic ratio but do not modify the sensitivity of any index.

  2. Prone Hypofractionated Whole-Breast Radiotherapy Without a Boost to the Tumor Bed: Comparable Toxicity of IMRT Versus a 3D Conformal Technique

    Energy Technology Data Exchange (ETDEWEB)

    Hardee, Matthew E.; Raza, Shahzad; Becker, Stewart J.; Jozsef, Gabor; Lymberis, Stella C. [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States); Hochman, Tsivia; Goldberg, Judith D. [Division of Biostatistics, New York University School of Medicine, New York, NY (United States); DeWyngaert, Keith J. [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States); Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States)

    2012-03-01

    Purpose: We report a comparison of the dosimetry and toxicity of three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT) among patients treated in the prone position with the same fractionation and target of the hypofractionation arm of the Canadian/Whelan trial. Methods and Materials: An institutional review board-approved protocol identified a consecutive series of early-stage breast cancer patients treated according to the Canadian hypofractionation regimen but in the prone position. Patients underwent IMRT treatment planning and treatment if the insurance carrier approved reimbursement for IMRT; in case of refusal, a 3D-CRT plan was used. A comparison of the dosimetric and toxicity outcomes during the acute, subacute, and long-term follow-up of the two treatment groups is reported. Results: We included 97 consecutive patients with 100 treatment plans in this study (3 patients with bilateral breast cancer); 40 patients were treated with 3D-CRT and 57 with IMRT. IMRT significantly reduced the maximum dose (Dmax median, 109.96% for 3D-CRT vs. 107.28% for IMRT; p < 0.0001, Wilcoxon test) and improved median dose homogeneity (median, 1.15 for 3D-CRT vs. 1.05 for IMRT; p < 0.0001, Wilcoxon test) when compared with 3D-CRT. Acute toxicity consisted primarily of Grade 1 to 2 dermatitis and occurred in 92% of patients. Grade 2 dermatitis occurred in 13% of patients in the 3D-CRT group and 2% in the IMRT group. IMRT moderately decreased rates of acute pruritus (p = 0.03, chi-square test) and Grade 2 to 3 subacute hyperpigmentation (p = 0.01, Fisher exact test). With a minimum of 6 months' follow-up, the treatment was similarly well tolerated in either group, including among women with large breast volumes. Conclusion: Hypofractionated breast radiotherapy is well tolerated when treating patients in the prone position, even among those with large breast volumes. Breast IMRT significantly improves dosimetry but yields only a modest

  3. Novel transcriptome assembly and comparative toxicity pathway analysis in mahi-mahi (Coryphaena hippurus) embryos and larvae exposed to Deepwater Horizon oil

    Science.gov (United States)

    Xu, Elvis Genbo; Mager, Edward M.; Grosell, Martin; Hazard, E. Starr; Hardiman, Gary; Schlenk, Daniel

    2017-03-01

    The impacts of Deepwater Horizon (DWH) oil on morphology and function during embryonic development have been documented for a number of fish species, including the economically and ecologically important pelagic species, mahi-mahi (Coryphaena hippurus). However, further investigations on molecular events and pathways responsible for developmental toxicity have been largely restricted due to the limited molecular data available for this species. We sought to establish the de novo transcriptomic database from the embryos and larvae of mahi-mahi exposed to water accommodated fractions (HEWAFs) of two DWH oil types (weathered and source oil), in an effort to advance our understanding of the molecular aspects involved during specific toxicity responses. By high throughput sequencing (HTS), we obtained the first de novo transcriptome of mahi-mahi, with 60,842 assembled transcripts and 30,518 BLAST hits. Among them, 2,345 genes were significantly regulated in 96hpf larvae after exposure to weathered oil. With comparative analysis to a reference-transcriptome-guided approach on gene ontology and tox-pathways, we confirmed the novel approach effective for exploring tox-pathways in non-model species, and also identified a list of co-expressed genes as potential biomarkers which will provide information for the construction of an Adverse Outcome Pathway which could be useful in Ecological Risk Assessments.

  4. Comparative metalloproteomic approaches for the investigation proteins involved in the toxicity of inorganic and organic forms of mercury in rice (Oryza sativa L.) roots.

    Science.gov (United States)

    Li, Yunyun; Zhao, Jiating; Li, Yu-Feng; Xu, Xiaohan; Zhang, Bowen; Liu, Yongjie; Cui, Liwei; Li, Bai; Gao, Yuxi; Chai, Zhifang

    2016-07-13

    The toxicity mechanisms of rice roots under inorganic mercury (IHg) or methylmercury (MeHg) stress were investigated using metalloproteomic approaches. Rice seedlings were cultivated in nutrient solutions with IHg or MeHg for three weeks. Proteins were extracted from the roots and separated by two-dimensional electrophoresis (2-DE). Differentially expressed proteins were analyzed using ESI-MS/MS and identified by PMF. 26 and 29 protein spots were differentially expressed in the IHg- and MeHg-exposed roots, respectively. The proteins responsive to Hg exposure are involved in antioxidative defense, sulfur and glutathione metabolism, carbohydrate and energy metabolism, programmed cell death, and pathogen defense. Chitinase and salt stress-induced proteins exhibited a greater differentially expression in response to MeHg stress compared to IHg stress. Hg-binding proteins were detected by the combined use of 1-DE, SRXRF, and ESI-MS/MS. The results showed that Hg was bound to proteins of 15-25 kDa in rice roots under Hg stress. The Hg contents in the band under IHg stress were remarkably higher than those under MeHg. Hg binds to proteins, which leads to irreversible damage of root growth. Rice roots changed the related protein expression levels in response to Hg stress. These results may provide new insights into the mechanism of toxicity of IHg and MeHg in rice.

  5. Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure.

    Science.gov (United States)

    Yaqoob, Noreen; Evans, Andrew; Foster, John R; Lock, Edward A

    2014-09-02

    Trichloroethylene (TCE) is widely used as a cleaning and decreasing agent and has been shown to cause liver tumours in rodents and a small incidence of renal tubule tumours in male rats. The basis for the renal tubule injury is believed to be related to metabolism of TCE via glutathione conjugation to yield the cysteine conjugate that can be activated by the enzyme cysteine conjugate β-lyase in the kidney. More recently TCE and its major metabolite trichloroethanol (TCE-OH) have been shown to cause formic aciduria which can cause renal injury after chronic exposure in rats. In this study we have compared the renal toxicity of TCE and TCE-OH in rats to try and ascertain whether the glutathione pathway or formic aciduria can account for the toxicity. Male rats were given TCE (500mg/kg/day) or TCE-OH at (100mg/kg/day) for 12 weeks and the extent of renal injury measured at several time points using biomarkers of nephrotoxicity and prior to termination assessing renal tubule cell proliferation. The extent of formic aciduria was also determined at several time points, while renal pathology and plasma urea and creatinine were determined at the end of the study. TCE produced a very mild increase in biomarkers of renal injury, total protein, and glucose over the first two weeks of exposure and increased Kim-1 and NAG in urine after 1 and 5 weeks exposure, while TCE-OH did not produce a consistent increase in these biomarkers in urine. However, both chemicals produced a marked and sustained increase in the excretion of formic acid in urine to a very similar extent. The activity of methionine synthase in the liver of TCE and TCE-OH treated rats was inhibited by about 50% indicative of a block in folate synthesis. Both renal pathology and renal tubule cell proliferation were reduced after TCE and TCE-OH treatment compared to controls. Our findings do not clearly identify the pathway which is responsible for the renal toxicity of TCE but do provide some support for metabolism

  6. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  7. Renal Artery Stent Outcomes

    Science.gov (United States)

    Murphy, Timothy P.; Cooper, Christopher J.; Matsumoto, Alan H.; Cutlip, Donald E.; Pencina, Karol M.; Jamerson, Kenneth; Tuttle, Katherine R.; Shapiro, Joseph I.; D’Agostino, Ralph; Massaro, Joseph; Henrich, William; Dworkin, Lance D.

    2016-01-01

    BACKGROUND Multiple randomized clinical trials comparing renal artery stent placement plus medical therapy with medical therapy alone have not shown any benefit of stent placement. However, debate continues whether patients with extreme pressure gradients, stenosis severity, or baseline blood pressure benefit from stent revascularization. OBJECTIVES The study sought to test the hypothesis that pressure gradients, stenosis severity, and/or baseline blood pressure affects outcomes after renal artery stent placement. METHODS Using data from 947 patients with a history of hypertension or chronic kidney disease from the largest randomized trial of renal artery stent placement, the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study, we performed exploratory analyses to determine if subsets of patients experienced better outcomes after stent placement than the overall cohort. We examined baseline stenosis severity, systolic blood pressure, and translesion pressure gradient (peak systolic and mean) and performed interaction tests and Cox proportional hazards analyses for the occurrence of the primary endpoint through all follow-up, to examine the effect of these variables on outcomes by treatment group. RESULTS There were no statistically significant differences in outcomes based on the examined variables nor were there any consistent nonsignificant trends. CONCLUSIONS Based on data from the CORAL randomized trial, there is no evidence of a significant treatment effect of the renal artery stent procedure compared with medical therapy alone based on stenosis severity, level of systolic blood pressure elevation, or according to the magnitude of the transstenotic pressure gradient. (Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions [CORAL]; NCT00081731) PMID:26653621

  8. [Renal abnormalities in ankylosing spondylitis].

    Science.gov (United States)

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  9. Comparative toxicity and micronuclei formation in Tribolium castaneum, Callosobruchus maculatus and Sitophilus oryzae exposed to high doses of gamma radiation.

    Science.gov (United States)

    Ahmadi, Mehrdad; Mozdarani, Hossein; Abd-Alla, Adly M M

    2015-07-01

    The effects of gamma radiation on mortality and micronucleus formation in Tribolium castaneum Herbst, Callosobruchus maculatus (F.) and Sitophilus oryzae (L.) genital cells were evaluated. Two groups of healthy and active adult insects 1-3 and 8-10 days old were irradiated with various doses (50-200 Gy) gamma ray. Seven days post-irradiation; mortality rates and micronucleus formation were assessed in genital cells of the irradiated insects. The results show that with increasing gamma doses, the mortality rate of each species increased and T. castaneum and S. oryzae showed the low and high sensitivity respectively. It was shown that the micronucleus appearance in the tested insects had correlation with amount and intensity of radiation doses. Moreover our results indicate different levels in the genotoxicity of gamma radiation among the insects' genital cells under study. The frequency of micronuclei in genital cells of 1-3 days old insects exposed to 50 and 200 Gy were 12.6 and 38.8 Mn/1000 cells in T. castaneum, 20.8 and 46.8 Mn/1000 cells in C. maculatus and 16.8 and 57.2 Mn/1000 cells in S. oryzae respectively. A high sensitivity of the genital cells to irradiation exposure was seen in S. oryzae correlated with its high mortality rate compared with the other two species. These results might be indicative of inflicting chromosomal damage expressed as micronucleus in high mortality rates observed in the pest population; an indication of genotoxic effects of radiation on the studied species.

  10. An open-label, randomized, controlled, 4-week comparative clinical trial of barnidipine hydrochloride, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in Chinese patients with renal parenchymal hypertension.

    Science.gov (United States)

    Chen, X; Zheng, F; Chen, P; Tang, L; Wei, R; Yu, Y; Su, Y; Kikkawa, T; Yamamoto, M

    2006-01-01

    This study compared barnidipine, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in 85 Chinese patients with renal parenchymal hypertension (diastolic blood pressure range 95 - 110 mmHg). Patients were randomly assigned to receive either 10 mg barnidipine or 10 mg benazepril orally daily for 4 weeks. In patients with diastolic blood pressure > 90 mmHg after 2 weeks of treatment, the dose of barnidipine or benazepril was increased by 5 or 10 mg, respectively. Both the barnidipine-treated group (n = 43) and the benazepril-treated group (n = 42) showed significant mean reductions from baseline in sitting systolic and diastolic blood pressures. The decrease in diastolic blood pressure with benazepril was significantly greater than with barnidipine treatment. Sitting heart rate was not changed by either drug. There was no significant difference in adverse events between the two groups. Barnidipine is similar to benazepril for the treatment of renal parenchymal hypertension.

  11. Comparative study of activities in reactive oxygen species production/defense system in mitochondria of rat brain and liver, and their susceptibility to methylmercury toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mori, N.; Hirayama, K. [Kumamoto University, School of Health Science, Kumamoto (Japan); Yasutake, A. [National Institute for Minamata Disease, Minamata (Japan)

    2007-11-15

    The involvement of oxidative stress has been suggested as a mechanism for neurotoxicity caused by methylmercury (MeHg), but the mechanism for MeHg selective toxicity in the central nervous system is still unclear. In this research, to clarify the mechanism of selective neurotoxicity caused by MeHg, the oxygen consumption levels, the reactive oxygen species (ROS) production rates and several antioxidant levels in mitochondria were compared among the cerebrum, cerebellum and liver of male Wistar rats. In addition, the alterations of these indexes were examined in MeHg-intoxicated rats (oral administration of 10 mg/kg day, for 5 days). Although the cerebrum and cerebellum in intact rats showed higher mitochondrial oxygen consumption levels and ROS production rates than the liver, glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities were much lower in the cerebrum and cerebellum than in the liver. Especially, the cerebellum showed the highest oxygen consumption and ROS production rate and the lowest mitochondrial glutathione (GSH) levels among the tissues examined. In the MeHg-treated rats, decrease in the oxygen consumption and increase in the ROS generation were found only in the cerebellum mitochondria, despite a lower Hg accumulation in the mitochondrial fraction compared to the liver. Since MeHg treatment produced an enhancement of ROS generation in cerebellum mitochondria supplemented with succinate substrates, MeHg-induced oxidative stress might affect the complex II-III mediated pathway in the electron transfer chain in the cerebellum mitochondria. Our study suggested that inborn factors, high production system activity and low defense system activity of ROS in the brain, would relate to the high susceptibility of the central nervous system to MeHg toxicity. (orig.)

  12. [Acetaminophen (paracetamol) causing renal failure: report on 3 pediatric cases].

    Science.gov (United States)

    Le Vaillant, J; Pellerin, L; Brouard, J; Eckart, P

    2013-06-01

    Renal failure secondary to acetaminophen poisoning is rare and occurs in approximately 1-2 % of patients with acetaminophen overdose. The pathophysiology is still being debated, and renal acetaminophen toxicity consists of acute tubular necrosis, without complication if treated promptly. Renal involvement can sometimes occur without prior liver disease, and early renal manifestations usually occur between the 2nd and 7th day after the acute acetaminophen poisoning. While therapy is exclusively symptomatic, sometimes serious metabolic complications can be observed. The monitoring of renal function should therefore be considered as an integral part of the management of children with acute, severe acetaminophen intoxication. We report 3 cases of adolescents who presented with acute renal failure as a result of voluntary drug intoxication with acetaminophen. One of these 3 girls developed severe renal injury without elevated hepatic transaminases. None of the 3 girls' renal function required hemodialysis, but one of the 3 patients had metabolic complications after her acetaminophen poisoning.

  13. Renal Aspects of Peptic Ulcer Pharmacology

    Directory of Open Access Journals (Sweden)

    Daniel Muruve

    1992-01-01

    Full Text Available Medications to treat peptic ulcer disease are used widely and may have adverse effects on renal function. Similarly, renal dysfunction may alter the pharmacokinetics of this diverse group of medications resulting in dosage adjustments. The older agents, antacids and sucralfate, allow absorption of cations (calcium, magnesium and aluminum which may result in toxicity. Newer medications (H2 blockers and omeprazole appear to have fewer side effects and be better tolerated with appropriate dosage adjustments.

  14. Hemin Attenuates Cisplatin-Induced Acute Renal Injury in Male Rats