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Sample records for renal effects evolution

  1. Renal effects of percutaneous stone removal

    SciTech Connect

    Eshghi, M.; Schiff, R.G.; Smith, A.D.

    1989-02-01

    Preoperative and postoperative renography with 99mTechnetium-diethylene-triamine pentaacetic acid was performed on 33 patients who were free of renal scarring, infection, and obstruction and who underwent percutaneous renal stone removal. Although there was a transient decrease in renal function postoperatively in some patients, statistically significant reductions in renal function occurred only in 1 patient with an arteriovenous malformation that was embolized and in 1 patient who had a postoperative ureteropelvic junction stricture. The creation of more than one nephrostomy tract did not affect the results. In the absence of serious complications, percutaneous nephrostomy does not have a significant effect on renal function.

  2. The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

    PubMed Central

    Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

    2015-01-01

    Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

  3. Effects of phospholipids on renal function.

    PubMed

    Buckalew, V M; Strandhoy, J W; Handa, R K

    1993-01-01

    The effects of two classes of phospholipids (PL) on renal function have been studied. Bolus injections of 1 ng (10 pmol) of lysophosphatidylcholine (LPC) caused natriuresis and diuresis in rats. Natriuretic activity was eliminated by substituting unsaturated bonds in the 1-acyl group and by removing the choline group on the sn-3 position. Natriuretic activity was not affected by substitution of 1-alkyl for 1-acyl groups. In the dog, LPC was natriuretic when given as a bolus of 3.0 micrograms/kg or as a constant infusion at 5 ng/kg/min. To explore further the effect of alkyl PLs on renal function, a series of studies with platelet activating factor (PAF) was performed. PAF injected directly into the renal artery (IR) in bolus doses of 0.5-10 ng/kg caused renal vasodilation that was blocked by a specific PAF receptor antagonist. This effect was not due to release of vasodilatory eicosanoids, dopamine, or nitric oxide (NO). PAF given IR as a continuous infusion at 2.5 ng/kg/min attenuated the renal vasoconstrictor effects of angiotensin II and norepinephrine but not vasopressin. This effect to attenuate vasoconstriction was blocked by the NO inhibitor N-monomethyl-L-arginine. These studies using picomolar amounts of PL suggest a physiologic role for these compounds in control of renal function. PMID:7508037

  4. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  5. Effects of renal lymphatic occlusion and venous constriction on renal function.

    PubMed Central

    Stolarczyk, J.; Carone, F. A.

    1975-01-01

    The effects of renal lymphatic occlusion or increased lymph flow due to renal vein constriction on renal function were investigated in rats. In each experiment, the renal lymphatics or vein of the left kidney were occluded or constricted and the right kidney served as a control. Occlusion of renal lymphatics caused renal enlargement, no change in glomerular filtration rate, a marked increase in urine flow and solute excretion without any change in urine osmolality, and enhanced urinary loss of urea, potassium, sodium and ammonium. Urea concentrations in medullary and papillary tissues were significantly elevated. Renal vein constriction caused renal enlargement and a marked drop in glomerular filtration rate, urine volume, urine osmolality and solute excretion. tissue concentrations of urea and potassium were decreased in the medulla and papilla and total tissue solute was significantly decreased in the papilla. The data indicate that in the rat, renal lymphatic occlusion traps urea in the medulla and induces a urea diuresis resulting in a large flow of normally concentrated urine. On the other hand, increased lymph flow secondary to renal vein constriction decreases medullary urea and potassium concentrations and papillary osmolality. These changes and the reduced glomerular filtration rate result in a small flow if dilute urine. Thus both renal lymphatic occlusion and enhanced lymph flow have a significant effect on renal function. Images Fig 1 PMID:1122006

  6. Effect of tobacco smoking on renal function.

    PubMed

    Cooper, Ross G

    2006-09-01

    Nicotine is one of many substances that may be acquired through active and passive smoking of tobacco. In man, nicotine is commonly consumed via smoking cigarettes, cigars or pipes. The addictive liability and pharmacological effects of smoking are primarily mediated by the major tobacco alkaloid nicotine. High stress jobs favour repeated smoking and further reinforce addictive behaviours. There are elevated serum cadmium and lead levels in smokers resulting in glomerular dysfunction. Nephropathies are accelerated by nicotine with an increased incidence of microalbuminuria progressing to proteinuria, followed by type-1 diabetes mellitus induced renal failure. Cigarette smoke-induced renal damage is due, at least in part, to activation of the sympathetic nervous system resulting in an elevation in blood pressure. Ethanol, nicotine, or concurrent intake significantly increases lipid peroxidation in liver, and decreased superoxide dismutase activity and increased catalase activity in the kidney. This review describes the effects of nicotine, smoking, smoke extracts and other tobacco constituents on renal and cardiovascular functions, and associated effects on the nervous system. Both active and passive smoking is toxic to renal function. PMID:17085829

  7. Numerical Investigation of Angulation Effects in Stenosed Renal Arteries

    PubMed Central

    Mortazavinia, Z; Arabi, S; Mehdizadeh, A R

    2014-01-01

    Background: Numerical study of angulation effects of renal arteries on blood flow has been of great interest for many researchers. Objective: This paper aims at numerically determining the angulation effects of stenosed renal arteries on blood flow velocity and renal mass flow. Method: An anatomically realistic model of abdominal aorta and renal arteries is reconstructed from CT-scan images and used to conduct numerical simulation of pulsatile non-Newtonian blood flow incorporating fluid-structure interaction. The renal arteries in the realistic model have left and right branch angles of 53˚ and 45˚, respectively. Atrapezium shape stenosis is considered in the entrance of right renal artery. Two other branch angles, i.e. 90 and 135˚, are also considered for right renal artery to study the angulation effects. Results: Comparison between models with right renal branch angles of 45˚, 90˚ and 135˚ reveals that high curvature of streamlines in the entrance of the renal artery with the angle of 135˚ causes the flow velocity and renal mass flow to be less than those of 45˚and 90˚. Conclusion: It is concluded that large renal branch angles cause the arteries to be unable to deliver blood in the requisite amounts to kidney. Kidney responds to counteract low blood flow by activating the renin-angiotension system which leads to severe hypertension. PMID:25505762

  8. Evolution of Renal Cysts to Anaplastic Sarcoma of Kidney in a Child With DICER1 Syndrome.

    PubMed

    Wu, Mona Kay; Goudie, Catherine; Druker, Harriet; Thorner, Paul; Traubici, Jeffrey; Grant, Ronald; Albrecht, Steffen; Weber, Evan; Charles, Adrian; Priest, Jack R; Fabian, Marc Robert; Foulkes, William D

    2016-07-01

    Anaplastic sarcoma of kidney (ASK) is a rare neoplasm recently associated with DICER1 mutations. We report a child with germline DICER1 mutation who developed ASK in preexisting septated renal cysts, which were likely cystic nephroma. From age 2.5 to 6 years, sonographic imaging illustrated changes in the size and number of renal cysts, followed at age 8.8 years by a mass, pathologically an ASK. Lung cysts resected in infancy were diagnosed retrospectively as pleuropulmonary blastoma. Both tumors had acquired somatic DICER1 mutations. Ultrasonographic evolution of renal cysts to ASK has not previously been documented. Children with both pulmonary and renal cysts are candidates for DICER1 mutation testing. PMID:26928971

  9. Effects of Renal Denervation on Renal Artery Function in Humans: Preliminary Study

    PubMed Central

    Doltra, Adelina; Hartmann, Arthur; Stawowy, Philipp; Goubergrits, Leonid; Kuehne, Titus; Wellnhofer, Ernst; Gebker, Rolf; Schneeweis, Christopher; Schnackenburg, Bernhard; Esler, Murray; Fleck, Eckart; Kelle, Sebastian

    2016-01-01

    Aim To study the effects of RD on renal artery wall function non-invasively using magnetic resonance. Methods and Results 32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble®). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders. Conclusions RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress. PMID:27003912

  10. Effect of Pneumoperitoneum on Renal Function and Physiology in Patients Undergoing Robotic Renal Surgery

    PubMed Central

    Sodha, Serena; Nazarian, Scarlet; Adshead, James M.; Vasdev, Nikhil; Mohan-S, Gowrie

    2016-01-01

    Laparoscopic and minimally-invasive robotic access has transformed the delivery of urological surgery. While associated with numerous desirable outcomes including shorter post-operative stay and faster return to preoperative function, these techniques have also been associated with increased morbidity such as reduced renal blood flow and post-operative renal dysfunction. The mechanisms leading to these renal effects complex and multifactorial, and have not been fully elucidated. However they are likely to include direct effects from raised intra-abdominal pressure, and indirect effects secondary to carbon dioxide absorption, neuroendocrine factors and tissue damage from oxidative stress. This review summarises these factors, and highlights the need for further work in this area, to direct novel therapies and guide alterations in technique with the aim of reducing renal dysfunction post-laparoscopic and robotic surgery. PMID:26989363

  11. [Surgical renal biopsies: technique, effectiveness and complications].

    PubMed

    Pinsach Elías, L; Blasco Casares, F J; Ibarz Servió, L; Valero Milián, J; Areal Calama, J; Bucar Terrades, S; Saladié Roig, J M

    1991-01-01

    Retrospective study made on 140 renal surgical biopsies (RSB) performed throughout the past 4 years in our Unit. The technique's effectiveness and morbidity are emphasized and the surgical technique and type of anaesthesia described. The sample obtained was enough to perform an essay in 100% cases, and a diagnosis was reached in 98.5%. Thirty-nine patients (27.8%) presented complications, 13 (9.2%) of which were directly related to the surgical technique. No case required blood transfusion and no deaths were reported. The type of anaesthesia used was: local plus sedation in 104 (74.2%) cases, rachianaesthesia in 10 (7.1%) and general in 26 (18.5%). The same approach was used in all patients: minimal subcostal lumbotomy, using Wilde's forceps to obtain the samples. It is believed that RSB is a highly effective, low mortality procedure, easy and quick to perform, and suitable for selected patients. PMID:1927642

  12. Renal effects of uranium in drinking water.

    PubMed Central

    Kurttio, Päivi; Auvinen, Anssi; Salonen, Laina; Saha, Heikki; Pekkanen, Juha; Mäkeläinen, Ilona; Väisänen, Sari B; Penttilä, Ilkka M; Komulainen, Hannu

    2002-01-01

    Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L. PMID:11940450

  13. FUNCTIONAL CONSEQUENCES OF PRENATAL METHYLMERCURY EXPOSURE: EFFECTS ON RENAL AND HEPATIC RESPONSES TO TROPHIC STIMULI AND ON RENAL EXCRETORY MECHANISMS

    EPA Science Inventory

    The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal activity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation ...

  14. Cognitive and emotional effects of renal transplantation

    PubMed Central

    Pawar, A.A.; Rathod, J.; Chaudhury, S.; Saxena, S.K.; Saldanha, D.; Ryali, V.S.S.R.; Srivastava, K.

    2006-01-01

    Background: Recent studies have shown a high prevalence of depression and cognitive changes in patients with end-stage renal disease (ERSD) and renal transplant recipients. There are few data available on the cognitive and emotional changes in patients undergoing renal transplantation in India. Aim: To evaluate the changes in cognitive profile and depression in renal transplant recipients. Methods: Thirty consecutive patients undergoing renal transplantation were evaluated 1 month before and 3 months after successful renal transplant with Beck Depression Inventory (BDI), Weschler Adult Performance Intelligence Scale (WAPIS), Luria Nebraska Neuropsychological battery (LNNB) and Life satisfaction scale. Results: Our study revealed an 86.7% prevalence of depression in ESRD patients as compared to 56.7% in post renal transplant patients. Analysis of neurocognitive functions on LNNB did not reveal any significant impairment. Furthermore, analysis of the Life satisfaction scale revealed most of the patients scored high satisfaction levels despite the stress of their disease. Results on WAPIS brought out significant improvement in intelligence quotient (IQ) after renal transplantation. Conclusion: Successful renal transplant is associated with improvement in depression, IQ and life satisfaction. PMID:20703410

  15. The effect of mannitol on renal function after cardiopulmonary bypass in patients with established renal dysfunction.

    PubMed

    Smith, M N A; Best, D; Sheppard, S V; Smith, D C

    2008-07-01

    The usefulness of mannitol in the priming fluid for cardiopulmonary bypass is uncertain in patients with normal renal function, and has not been studied in patients with established renal dysfunction. We studied 50 patients with serum creatinine between 130 and 250 micromol.l(-1) having cardiac surgery. Patients were randomised to receive mannitol 0.5 g.kg(-1), or an equivalent volume of Hartmann's solution, in the bypass prime. There were no differences between the groups in plasma creatinine or change in creatinine from baseline, urine output, or fluid balance over the first three postoperative days. We conclude that mannitol has no effect on routine measures of renal function during cardiac surgery in patients with established renal dysfunction. PMID:18582254

  16. Effect of increased protein intake on renal acid load and renal hemodynamic responses.

    PubMed

    Teunissen-Beekman, Karianna F M; Dopheide, Janneke; Geleijnse, Johanna M; Bakker, Stephan J L; Brink, Elizabeth J; de Leeuw, Peter W; van Baak, Marleen A

    2016-03-01

    Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high-protein diets reduce renal function. Effects of acute and 4-week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy-nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty-four-hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein- or maltodextrin-load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P ≤ 0.001). Postprandial filtration fraction decreased further after the protein-supplemented breakfast than after the maltodextrin-supplemented breakfast after 4 weeks of supplementation (P ≤ 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin-converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function. PMID:26997623

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

    PubMed

    Nakamura, Kazuyoshi; Komagiri, You; Kubokawa, Manabu

    2012-02-01

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

  18. The effects of a unilateral ultrasound-guided renal biopsy on renal function in healthy sedated cats.

    PubMed

    Drost, W T; Henry, G A; Meinkoth, J H; Woods, J P; Payton, M E; Rodebush, C

    2000-01-01

    Complications of renal biopsies are well documented except for the change in renal function after a biopsy. Eighteen healthy, adult cats were divided into two groups (n = 9 cats/group). For the measurement of global and split renal function, Group 1 used the renal uptake of 99mTc-DTPA and Group 2 used the renal uptake of 99mTc-MAG3. Scintigraphic data were collected on days (-4), (-3), 0, 1, 2, and 4 post renal biopsy. Using ultrasound guidance, biopsies were taken from the right renal cortex on dO, before acquiring scintigraphic images. P - values less than 0.10 were considered significant due to the limited number of observations. The only statistically significant change (p = 0.08) in global renal function detected was by day following a unilateral renal biopsy. Cats imaged using 99mTc-MAG3 had discernible liver activity. A unilateral, ultrasound guided renal biopsy has minimal effect on renal function in normal, healthy sedated cats. PMID:10695882

  19. Renal effects of amphotericin B lipid complex.

    PubMed

    Luke, R G; Boyle, J A

    1998-05-01

    A study was conducted to compare the renal effects of amphotericin B lipid complex (ABLC), a lipid formulation of the widely used antifungal medication, with conventional amphotericin B (AmB) in the treatment of serious fungal infections, including invasive candidiasis, cryptococcal meningitis, and aspergillosis. The clinical experience of ABLC includes two types of open-label studies: randomized comparative (ABLC 5 mg/kg/d compared with AmB 0.6 to 1 mg/kg) and emergency use. In the comparative studies, changes in serum creatinine were evaluated three ways: doubling of the baseline value, an increase from < or = 1.5 mg/dL at baseline to > or = 1.5 mg/dL, and an increase from < or = 1.5 mg/dL at baseline to > or = 2.0 mg/dL. More patients in the AmB group reached these end points than in the ABLC group (P < or = 0.007), and the time needed to reach each of these end points was significantly shorter for the AmB group (P < or = 0.02). Increased serum creatinine was reported as an adverse event more frequently by patients receiving AmB than by patients receiving ABLC. In the emergency use study, a steady and statistically significant decrease in serum creatinine was observed among patients who started ABLC treatment with serum creatinine greater than 2.5 mg/dL due to prior AmB treatment. ABLC offers the physician a valuable, less-nephrotoxic alternative to AmB for the treatment of patients with severe, invasive fungal infections. PMID:9590187

  20. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero G in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Four rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast, five of the seven remaining rats increased the fraction of the filtered sodium excreted and their urinary flow rate. Potassium excretion increased. End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause in the rat a decrease in distal tubular sodium and water reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis. The adequacy of other nonatrial volume control mechanisms in regulating renal salt and water conservation in opposition to the studied atrial-renal (Henry-Gauer) reflex of thoracic vascular distension is confirmed.

  1. Effects of renal failure on drug transport and metabolism.

    PubMed

    Sun, Hong; Frassetto, Lynda; Benet, Leslie Z

    2006-01-01

    for drugs that are not renally excreted are consistent with uremic toxin effects on either intestinal or hepatic cell transporters, metabolizing enzymes, or both. In conclusion, alterations of drug transporters, as well as metabolic enzymes, in patients with renal failure can be responsible for reduced drug clearance. PMID:16085315

  2. The effect of ketone bodies on renal ammoniogenesis

    PubMed Central

    Lemieux, Guy; Vinay, Patrick; Robitaille, Pierre; Plante, Gérard E.; Lussier, Yolande; Martin, Pierre

    1971-01-01

    Infusion of ketone bodies to ammonium chloride-loaded acidotic dogs was found to induce significant reduction in urinary excretion of ammonia. This effect could not be attributed to urinary pH variations. Total ammonia production by the left kidney was measured in 25 animals infused during 90 min with the sodium salt of D,L-β-hydroxybutyric acid adjusted to pH 6.0 or 4.2. Ketonemia averaged 4.5 mM/liter. In all experiments the ammonia content of both urine and renal venous blood fell markedly so that ammoniogenesis was depressed by 60% or more within 60 min after the onset of infusion. Administration of equimolar quantities of sodium acetoacetate adjusted to pH 6.0 resulted in a 50% decrease in renal ammonia production. Infusion of ketone bodies adjusted to pH 6.0 is usually accompanied by a small increase in extracellular bicarbonate (3.7 mM/liter). However infusion of D,L-sodium lactate or sodium bicarbonate in amounts sufficient to induce a similar rise in plasma bicarbonate resulted in only a slight decrement in ammonia production (15%). The continuous infusion of 5% mannitol alone during 90-150 min failed to influence renal ammoniogenesis. Infusion of pure sodium-free β-hydroxybutyric acid prepared by ion exchange (pH 2.2) resulted in a 50% decrease in renal ammoniogenesis in spite of the fact that both urinary pH and plasma bicarbonate fell significantly. During all experiments where ketones were infused, the renal extraction of glutamine became negligible as the renal glutamine arteriovenous difference was abolished. Renal hemodynamics did not vary significantly. Infusion of β-hydroxybutyrate into the left renal artery resulted in a rapid decrease in ammoniogenesis by the perfused kidney. The present study indicates that ketone bodies exert their inhibitory influence within the renal tubular cell. Since their effect is independent of urinary or systemic acid-base changes, it is suggested that they depress renal ammoniogenesis by preventing the

  3. The effects of tempol on renal function and hemodynamics in cyclosporine-induced renal insufficiency rats.

    PubMed

    Chia, Tan Y; Sattar, Munavvar A; Abdulla, Mohammed H; Rathore, Hassaan A; Ahmad, Fiaz ud Din; Kaur, Gurjeet; Abdullah, Nor A; Johns, Edward J

    2013-08-01

    This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p < 0.05), respectively. Tempol treatment in TCs or TLCs prevented the increase in blood pressure and improved creatinine clearance and sodium excretion compared to untreated Cs. The renal vasoconstriction in Cs or LCs to NA, PE and Ang II were lower than control by ∼35-48% (all p < 0.05). In TCs or TLCs, there was enhanced renal vasoconstriction to all agonist by ∼39-114% compared to Cs. SOD is important to counterbalance the hypertensive effect of a defective NO system and to allow the normal vasoconstrictor response of the renal vasculature to adrenergic agonists and Ang II in a model of CsA-induced renal insufficiency. PMID:23822648

  4. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.; Discala, V. A.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero g or space, in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast 5 of the 7 remaining rats increased the fraction of the filtered sodium excreted (C sub Na/GFR, p .05) and their urinary flow rate (V, p .05). Potassium excretion increased (U sub k V, p .05). End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause, in rats, a decrease in distal tubular sodium, water and potassium reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis.

  5. Effect of renal sympathetic nerve on adrenergically and angiotensin II-induced renal vasoconstriction in normal Wistar-Kyoto rats

    PubMed Central

    2011-01-01

    Background This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats. Methods Forty-eight WKY rats were treated with either losartan (10 mg/kg/day p.o.) or carvedilol (5 mg/kg/day p.o.) or a combination of them (10 mg/kg/day + 5 mg/kg/day p.o.) for 7 days. On day 8, the rats were anaesthetized, and renal vasoconstrictor experiments were carried out. A group of rats was subjected to acute unilateral renal denervation during the acute study. Changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by Ang II, noradrenaline (NA), and methoxamine (ME). Results In normal animals, losartan decreased (P < 0.05) the renal vasoconstrictor response to Ang II but not to NA or ME. Carvedilol treatment, however, blunted (P < 0.05) the renal vasoconstrictor responses to Ang II and adrenergic agonists. Combination of losartan and carvedilol blunted (P < 0.05) the renal vasoconstrictor response to Ang II but augmented the responses to NA and ME (all P < 0.05). Interestingly, when denervated rats were treated with the same combination, there was a reduction (P < 0.05) in the renal vasoconstrictor responses to Ang II and adrenergic agonists. Conclusions Data suggest that the renal sympathetic nerve contributes to adrenergic agonist-mediated renal vasoconstrictions in normal rats. The data further indicate an interactive relationship between renin-angiotensin and sympathetic nervous systems in modulating adrenergically and Ang II-induced renal vasoconstriction in WKY rats. PMID:21047287

  6. Renal dysfunction after total body irradiation: Dose-effect relationship

    SciTech Connect

    Kal, Henk B. . E-mail: H.B.Kal@UMCUtrecht.nl; Kempen-Harteveld, M. Loes van

    2006-07-15

    Purpose: Late complications related to total body irradiation (TBI) as part of the conditioning regimen for hematopoietic stem cell transplantation have been increasingly noted. We reviewed and compared the results of treatments with various TBI regimens and tried to derive a dose-effect relationship for the endpoint of late renal dysfunction. The aim was to find the tolerance dose for the kidney when TBI is performed. Methods and Materials: A literature search was performed using PubMed for articles reporting late renal dysfunction. For intercomparison, the various TBI regimens were normalized using the linear-quadratic model, and biologically effective doses (BEDs) were calculated. Results: Eleven reports were found describing the frequency of renal dysfunction after TBI. The frequency of renal dysfunction as a function of the BED was obtained. For BED >16 Gy an increase in the frequency of dysfunction was observed. Conclusions: The tolerance BED for kidney tissue undergoing TBI is about 16 Gy. This BED can be realized with highly fractionated TBI (e.g., 6 x 1.7 Gy or 9 x 1.2 Gy at dose rates >5 cGy/min). To prevent late renal dysfunction, the TBI regimens with BED values >16 Gy (almost all found in published reports) should be applied with appropriate shielding of the kidneys.

  7. Effects of water immersion on renal hemodynamics in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Levinson, R.; Loutzenhiser, R.

    1976-01-01

    The present study was undertaken to delineate the effects of water immersion to the neck (NI) on renal plasma flow and glomerular filtration rate as assessed by the clearance of p-aminohippuric acid (PAH) and inulin, respectively. Nine normal male subjects were studied on two occasions, control and NI. The conditions of seated posture and time of day were identical. Immersion did not alter either clearance at a time when sodium excretion was increasing markedly. The constancy of PAH clearance during NI suggests that renal blood flow is unaltered and that the natriuresis of NI is mediated independently of alterations in overall renal perfusion. The sluggish decline of a natriuresis during recovery is consistent with the presence of a humoral factor contributing to the encountered natriuresis.

  8. Effects of microgravity on renal stone risk assessment

    NASA Technical Reports Server (NTRS)

    Pietrzyk, R. A.; Pak, C. Y. C.; Cintron, N. M.; Whitson, P. A.

    1992-01-01

    Physiologic changes induced during human exposure to the microgravity environment of space may contribute to an increased potential for renal stone formation. Renal stone risk factors obtained 10 days before flight and immediately after return to earth indicated that calcium oxalate and uric acid stone-forming potential was increased after space flights of 4-10 days. These data describe the need for examining renal stone risk during in-flight phases of space missions. Because of limited availability of space and refrigerated storage on spacecraft, effective methods must be developed for collecting urine samples in-flight and for preserving (or storing) them at temperatures and under conditions commensurate with mission constraints.

  9. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

    PubMed Central

    Varela, Ignacio; Fisher, Rosalie; McGranahan, Nicholas; Matthews, Nicholas; Santos, Claudio R; Martinez, Pierre; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Spencer-Dene, Bradley; Gulati, Sakshi; Bates, Paul A; Stamp, Gordon; Pickering, Lisa; Gore, Martin; Nicol, David L; Hazell, Steven; Futreal, P Andrew; Stewart, Aengus; Swanton, Charles

    2015-01-01

    Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development. PMID:24487277

  10. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing.

    PubMed

    Gerlinger, Marco; Horswell, Stuart; Larkin, James; Rowan, Andrew J; Salm, Max P; Varela, Ignacio; Fisher, Rosalie; McGranahan, Nicholas; Matthews, Nicholas; Santos, Claudio R; Martinez, Pierre; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Spencer-Dene, Bradley; Gulati, Sakshi; Bates, Paul A; Stamp, Gordon; Pickering, Lisa; Gore, Martin; Nicol, David L; Hazell, Steven; Futreal, P Andrew; Stewart, Aengus; Swanton, Charles

    2014-03-01

    Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73-75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development. PMID:24487277

  11. Predicting the effects of dietary manipulation in chronic renal disease

    SciTech Connect

    El Nahas, A.M.; Brady, S.A.; Masters-Thomas, A.; Wilkinson, V.; Hilson, A.J.W.; Moorhead, J.F.

    1984-01-01

    It has been suggested that the progressive fall in renal function in some patients with CRF is due to hyperfusion of the remnant nephrons in response to the relatively high protein diet of modern life. The authors attempted to assess this and to see what was the shortest time in which any effect could be demonstrated. In the first phase, 39 patients with CRF had their renal function followed for 6 months on their normal diet and 6 months on a low-protein diet (LPD). The patients on LPD all showed an improvement in the rate of fall of renal function. This was marked in patients with mainly tubular disease, and poor in those with glomerular and vascular disease. In the second phase, 11 of these patients (and 1 other) were started on a high protein diet (HPD) for two weeks, and then switched back to a LPD for 2 weeks. There was no change in GFR during this period, but there were marked changes in ERPF, which correlated well with the changes in renal function in the first phase (r = 0.76, rho < 0.01); 4/4 patients with tubular disease showed a rise in ERPF on HPD and a fall on LPD, while only 4/8 with glomerular or vascular disease responded. In the third phase, they assessed the effect of a single high-protein meal in normal volunteers. This showed that there are major changes in hemodynamics following a meal, such that it is not possible to make any statement about renal function using the single-shot methods. The authors conclude that a 2-week period of HPD followed by LPD allows prediction of the possible beneficial response to diet in CRF; that this is best monitored by ERPF; and that a single meal may invalidate renal function measurement.

  12. Effects of opioid peptides on neural control of renal function in spontaneously hypertensive rats.

    PubMed

    Kapusta, D R; Jones, S Y; DiBona, G F

    1990-06-01

    The aims of the present study were to examine the effects of opioid receptor agonists and antagonists on the renal vascular (renal blood flow) and tubular (urinary sodium excretion) responses to renal nerve stimulation and norepinephrine in anesthetized spontaneously hypertensive rats (SHR). Graded frequency renal nerve stimulation (0.5-4.0 Hz) and doses of norepinephrine (10-80 ng/kg) produced frequency and dose-dependent decreases in renal blood flow. The renal vasoconstrictor responses were not altered by intravenous infusion of the opioid receptor agonists methionine enkephalin (mu and delta, 75 micrograms/kg/min) or U-50488H (kappa, 20 micrograms/kg/min) or administration of the opioid receptor antagonist naloxone (1 mg/kg i.v.). The antinatriuretic response to low frequency (less than 1.0 Hz) electrical renal nerve stimulation was prevented by naloxone but not affected by methionine enkephalin administration without changes in glomerular filtration rate or effective renal plasma flow. These studies suggest that endogenous opioid receptor mechanisms are involved in the increased renal tubular sodium reabsorption response to low frequency renal nerve stimulation but not in the renal vasoconstrictor response to either renal nerve stimulation or norepinephrine. This might occur by facilitation of the renal nerve terminal release, the direct renal tubular action, or both, of norepinephrine to influence renal tubular sodium reabsorption. PMID:2351429

  13. Renal Effects of Prostaglandins and Cyclooxygenase-2 Inhibitors

    PubMed Central

    2008-01-01

    Prostaglandins (PGs) with best-defined renal functions are PGE2 and prostacyclin (PGI2). These vasodilatory PGs increase renal blood flow and glomerular filtration rate under conditions associated with decreased actual or effective circulating volume, resulting in greater tubular flow and secretion of potassium. Under conditions of decreased renal perfusion, the production of renal PGs serves as an important compensatory mechanism. PGI2 (and possibly PGE2) increases potassium secretion mainly by stimulating secretion of renin and activating the renin-angiotensin system, which leads to increased secretion of aldosterone. In addition, PGE2 is involved in the regulation of sodium and water reabsorption and acts as a counterregulatory factor under conditions of increased sodium reabsorption. PGE2 decreases sodium reabsorption at the thick ascending limb of the loop of Henle probably via inhibition of the Na+-K+-2Cl- cotransporter type 2 (NKCC2). Cyclooxygenase inhibitors may enhance urinary concentrating ability in part through effects to upregulate NKCC2 in the thick ascending limb of Henle's loop and aquaporin-2 in the collecting duct. Thus, they may be useful to treat Bartter's syndrome and nephrogenic diabetes insipidus. PMID:24459520

  14. Renal protective effects of erythropoietin on ischemic reperfusion injury.

    PubMed

    Moriyama, Manabu T; Tanaka, Tatsuro; Morita, Nobuyo; Ishii, Takeo; Chikazawa, Ippei; Suga, Kodai; Miyazawa, Katsuhito; Suzuki, Koji

    2010-01-01

    While the problem of organ shortage has not yet been solved, the number of patients who need to be treated with dialysis due to end-stage renal disease (ESRD) is increasing each year. With the aim of eliminating dialytic therapy as much as possible, the opportunities for organ donation from expansive criteria donor (ECD) or marginal donors due to cardiac death have been increasing. With the purpose of extracting organs in a state in which the function is preserved as much as possible, we reexamined the conditions of tissue disorders resulting from temporary ischemia of the organs as well as changes in tissue function and the effects on the preservation of renal function over time by using rat models in order to clinically utilize erythropoietin, which has inhibitory effects on ischemia-reperfusion disorder, as has been conventionally reported. With 8- to 9-week-old Wister male rats, after the right kidney had been resected under general anesthesia, the left renal artery was clamped to inhibit the blood flow for 45 min. At 30 min before inhibiting the blood flow and after releasing the inhibited blood flow, 100 U/kg of recombinant human erythropoietin (rhEPO) was administered via the inferior vena cava and the abdominal cavity, and then the tissues and blood samples were extracted at 6 and 24 h after the release. The renal tissue specimens were evaluated using H&E staining and TUNEL staining in order to observe differences in the expression of apoptosis as well as the renal function and changes in the emergence of active oxygen were investigated by using samples that had been obtained from drawn blood. Moreover, we examined the degree of renal dysfunction by means of neutrophil gelatinase-associated lipocalin (NGAL) in the spot urine samples. The changes in renal function, which were observed according to the serum creatinine level, showed that the renal function was preserved with a significant difference in the rhEPO administration group. The liver deviation

  15. Recurrent chromosomal gains and heterogeneous driver mutations characterise papillary renal cancer evolution

    PubMed Central

    Kovac, Michal; Navas, Carolina; Horswell, Stuart; Salm, Max; Bardella, Chiara; Rowan, Andrew; Stares, Mark; Castro-Giner, Francesc; Fisher, Rosalie; de Bruin, Elza C.; Kovacova, Monika; Gorman, Maggie; Makino, Seiko; Williams, Jennet; Jaeger, Emma; Jones, Angela; Howarth, Kimberley; Larkin, James; Pickering, Lisa; Gore, Martin; Nicol, David L.; Hazell, Steven; Stamp, Gordon; O’Brien, Tim; Challacombe, Ben; Matthews, Nik; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Varela, Ignacio; Chandra, Ashish; Horsfield, Catherine; Polson, Alexander; Tran, Maxine; Bhatt, Rupesh; Terracciano, Luigi; Eppenberger-Castori, Serenella; Protheroe, Andrew; Maher, Eamonn; El Bahrawy, Mona; Fleming, Stewart; Ratcliffe, Peter; Heinimann, Karl; Swanton, Charles; Tomlinson, Ian

    2015-01-01

    Papillary renal cell carcinoma (pRCC) is an important subtype of kidney cancer with a problematic pathological classification and highly variable clinical behaviour. Here we sequence the genomes or exomes of 31 pRCCs, and in four tumours, multi-region sequencing is undertaken. We identify BAP1, SETD2, ARID2 and Nrf2 pathway genes (KEAP1, NHE2L2 and CUL3) as probable drivers, together with at least eight other possible drivers. However, only ~10% of tumours harbour detectable pathogenic changes in any one driver gene, and where present, the mutations are often predicted to be present within cancer sub-clones. We specifically detect parallel evolution of multiple SETD2 mutations within different sub-regions of the same tumour. By contrast, large copy number gains of chromosomes 7, 12, 16 and 17 are usually early, monoclonal changes in pRCC evolution. The predominance of large copy number variants as the major drivers for pRCC highlights an unusual mode of tumorigenesis that may challenge precision medicine approaches. PMID:25790038

  16. Recurrent chromosomal gains and heterogeneous driver mutations characterise papillary renal cancer evolution.

    PubMed

    Kovac, Michal; Navas, Carolina; Horswell, Stuart; Salm, Max; Bardella, Chiara; Rowan, Andrew; Stares, Mark; Castro-Giner, Francesc; Fisher, Rosalie; de Bruin, Elza C; Kovacova, Monika; Gorman, Maggie; Makino, Seiko; Williams, Jennet; Jaeger, Emma; Jones, Angela; Howarth, Kimberley; Larkin, James; Pickering, Lisa; Gore, Martin; Nicol, David L; Hazell, Steven; Stamp, Gordon; O'Brien, Tim; Challacombe, Ben; Matthews, Nik; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Varela, Ignacio; Chandra, Ashish; Horsfield, Catherine; Polson, Alexander; Tran, Maxine; Bhatt, Rupesh; Terracciano, Luigi; Eppenberger-Castori, Serenella; Protheroe, Andrew; Maher, Eamonn; El Bahrawy, Mona; Fleming, Stewart; Ratcliffe, Peter; Heinimann, Karl; Swanton, Charles; Tomlinson, Ian

    2015-01-01

    Papillary renal cell carcinoma (pRCC) is an important subtype of kidney cancer with a problematic pathological classification and highly variable clinical behaviour. Here we sequence the genomes or exomes of 31 pRCCs, and in four tumours, multi-region sequencing is undertaken. We identify BAP1, SETD2, ARID2 and Nrf2 pathway genes (KEAP1, NHE2L2 and CUL3) as probable drivers, together with at least eight other possible drivers. However, only ~10% of tumours harbour detectable pathogenic changes in any one driver gene, and where present, the mutations are often predicted to be present within cancer sub-clones. We specifically detect parallel evolution of multiple SETD2 mutations within different sub-regions of the same tumour. By contrast, large copy number gains of chromosomes 7, 12, 16 and 17 are usually early, monoclonal changes in pRCC evolution. The predominance of large copy number variants as the major drivers for pRCC highlights an unusual mode of tumorigenesis that may challenge precision medicine approaches. PMID:25790038

  17. Primary disease recurrence—effects on paediatric renal transplantation outcomes.

    PubMed

    Bacchetta, Justine; Cochat, Pierre

    2015-06-01

    Primary disease recurrence after renal transplantation is mainly diagnosed by examination of biopsy samples, but can also be associated with clinical symptoms. In some patients, recurrence can lead to graft loss (7-8% of all graft losses). Primary disease recurrence is generally associated with a high risk of graft loss in patients with focal segmental glomerulosclerosis, membranous proliferative glomerulonephritis, primary hyperoxaluria or atypical haemolytic uraemic syndrome. By contrast, disease recurrence is associated with a limited risk of graft loss in patients with IgA nephropathy, renal involvement associated with Henoch-Schönlein purpura, antineutrophil cytoplasmic antibody-associated glomerulonephritis or lupus nephritis. The presence of systemic diseases that affect the kidneys, such as sickle cell anaemia and diabetes mellitus, also increases the risk of delayed graft loss. This Review provides an overview of the epidemiology, pathophysiology and management of primary disease recurrence in paediatric renal graft recipients, and describes the overall effect on graft survival of each of the primary diseases listed above. With appropriate management, few paediatric patients should be excluded from renal transplantation programmes because of an increased risk of recurrence. PMID:25917555

  18. The Effects of Catheter-Based Radiofrequency Renal Denervation on Renal Function and Renal Artery Structure in Patients With Resistant Hypertension

    PubMed Central

    Zhang, Zhi-Hui; Yang, Kan; Jiang, Feng-Lin; Zeng, Li-Xiong; Jiang, Wei-Hong; Wang, Xiao-Yan

    2014-01-01

    There are no clinical studies on the effects of catheter-based radiofrequency renal denervation (RDN) on renal artery structure using 64-detector computed tomography (CT). A total of 39 patients with resistant hypertension received RDN and 38 patients received drug treatment. Mean systolic pressure and diastolic pressure in the RDN group decreased after 1, 3, 6, and 12 months of procedure (P<.05) and urinary protein level significantly decreased after 6 and 12 months (P<.05). The diameter, length, and sectional area of the renal artery; number of cases of atherosclerosis; and plaque burden of 64-detector CT renal arteriography did not change at 12 months of follow-up (P<.05), whereas the plaque burden increased significantly in the control group (P<.05). RDN significantly and persistently reduced blood pressure and decreased urinary protein excretion rate in patients with resistant hypertension and did not exhibit any adverse effect on renal function and renal artery structure. PMID:25039997

  19. The effects of environmental chemicals on renal function

    PubMed Central

    Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

    2015-01-01

    The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease. PMID:26100504

  20. The effects of environmental chemicals on renal function.

    PubMed

    Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

    2015-10-01

    The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease. PMID:26100504

  1. The effects of nanoparticles on the renal system.

    PubMed

    Iavicoli, Ivo; Fontana, Luca; Nordberg, Gunnar

    2016-07-01

    Through a process of translocation across biological barriers, nanoparticles can reach and deposit in secondary target organs where they may induce adverse biological reactions. Therefore, a correct assessment of nanoparticle-induced adverse effects should take into account the different aspects of toxicokinetics and tissues that may be targeted by nanoparticles. For this reason, a comprehensive evaluation of renal nanotoxicity is urgently needed as kidneys are particularly susceptible to xenobiotics and renal excretion is an expected and possible elimination route of nanoparticles in living organisms. On one hand, summarizing the findings of in vitro and in vivo studies that have investigated the adverse effects of nanoparticles on the kidney, this review intends to provide a thorough insight into the nephrotoxicity of these substances. The evaluation of the in vitro studies revealed that different types of nanoparticles (carbon, metal and/or silica nanoparticles) are able to exert significant cytotoxic effects (i.e., decreased cell viability, induction of oxidative stress, mitochondrial or cytoskeleton dysfunction and cell membrane and DNA damage). On the other hand, in vivo studies demonstrated that nanoparticles exhibited an important nephrotoxic potential both at tubular (i.e., degeneration of tubular epithelial cell, cellular fragments and proteinaceous liquid in tubule lumen, renal interstitial fibrosis) and glomerular level (i.e., swollen glomeruli, changes in Bowman's space and proliferation of mesangial cells). Although the data currently available indicate that nanoparticles may adversely impact the renal system, further studies are needed in order to clarify all the potential molecular mechanisms of nephrotoxicity induced by these xenobiotics, in particular at glomerular level. PMID:27195425

  2. Effect of amlodipine on mouse renal interstitial fibrosis.

    PubMed

    Honma, Shigeyoshi; Nakamura, Kazuki; Shinohara, Masahiro; Mitazaki, Satoru; Abe, Sumiko; Yoshida, Makoto

    2016-06-01

    Unilateral ureteral obstruction (UUO) is a well-established method to study interstitial fibrosis of the kidney. In this study, we investigated the effects of a calcium channel blocker, amlodipine, on UUO-induced renal interstitial fibrosis in mice. UUO significantly increased the fibrotic area in the obstructed kidney, but this change was inhibited by amlodipine (6.7mg/kg/day in drinking water). mRNA expression of heat shock protein (HSP) 47 and type IV collagen was increased in the kidneys of UUO mice. Amlodipine reduced the expression of both HSP47 and type IV collagen mRNAs. Phosphorylation of c-jun-N-terminal kinase (JNK) was significantly increased by UUO, but the change was inhibited by amlodipine. Collectively, these results suggest that amlodipine may inhibit the expression of HSP47 and type IV collagen by reducing phosphorylation of JNK and ameliorating the renal interstitial fibrosis induced by UUO. PMID:27029240

  3. Renal effects and vascular reactivity induced by Tityus serrulatus venom.

    PubMed

    de Sousa Alves, Renata; do Nascimento, Nilberto Robson Falcão; Barbosa, Paulo Sérgio Ferreira; Kerntopf, Marta Regina; Lessa, Lucília Maria Abreu; de Sousa, Clauber Mota; Martins, René Duarte; Sousa, Daniel Freire; de Queiroz, Maria Goretti Rodrigues; Toyama, Marcos Hikari; Fonteles, Manassés Claudino; Martins, Alice Maria Costa; Monteiro, Helena Serra Azul

    2005-09-01

    Tityus serrulatus, popularly known as yellow scorpion, is one of the most studied scorpion species in South America and its venom has supplied some highly active molecules. The effects of T. serrulatus venom upon the renal physiology in human showed increased renal parameters, urea and creatinine. However, in perfused rat kidney the effects were not tested until now. Isolated kidneys from Wistar rats, weighing 240-280 g, were perfused with Krebs-Henseleit solution containing 6% (g weight) of previously dialysed bovine serum albumin. The effects of T. serrulatus venom were studied on the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), sodium tubular transport (%TNa+), potassium tubular transport (%TK+) and chloride tubular transport (%TCl-). Tityus serrulatus venom (TsV; 10 microg/mL) was added to the system 30 min after the beginning of each experiment (n=6). This 30 min period was used as an internal control. The mesenteric bed was perfused with Krebs solution kept warm at 37 degrees C by a constant flow (4 mL/min), while the variable perfusion pressure was measured by means of a pressure transducer. The direct vascular effects of TsV (10 microg/mL/min; n=6), infused at a constant rate (0.1 mL/min), were examined and compared to the infusion of the vehicle alone at the same rate. TsV increased PP (PP30'=127.8+/-0.69 vs PP60'=154.2+/-14 mmHg*, *p<0.05) and RVR (RVR30'=6.29+/-0.25 vs RVR60'=8.03+/-0.82 mmHg/mLg(-1)min(-1)*, *p<0.05), decreased GFR (GFR30'=0.58+/-0.02 vs GFR60'=0.46+/-0.01mLg(-1)min(-1)*, *p<0.05) and UF (UF30'=0.135+/-0.001 vs UF60'=0.114+/-0.003mLg(-1)min(-1)*, *p<0.05). Tubular transport was not affected during the whole experimental period (120 min). On the other hand, the infusion of TsV (10 microg/mL/min) increased the basal perfusion pressure of isolated arteriolar mesenteric bed (basal pressure: 74.17+/-3.42 vs TsV 151.8+/-17.82 mmHg*, *p<0.05). TsV affects renal haemodynamics

  4. Neuropsychologic side-effects of tacrolimus in pediatric renal transplantation.

    PubMed

    Kemper, Markus J; Spartà, Giuseppina; Laube, Guido F; Miozzari, Marco; Neuhaus, Thomas J

    2003-04-01

    Calcineurin inhibition with tacrolimus has been used after renal transplantation (RTPL) as rescue therapy for insufficient immunological control or if cyclosporin A (CSA) toxicity occurred. Neurologic side-effects occur but are rare in children, usually presenting as tremor; however, serious complications, e.g. the posterior leukoencephalopathy syndrome are also documented. Twenty children (10 girls) were switched to tacrolimus: 11 (55%) for immunological reasons (n = 9: steroid-resistant rejection; n = 2: recurrent rejections) and nine for CSA side-effects. Tacrolimus was started at a median of 8 wk (range 10 d to 8.7 yr) after RTPL and was continued for a median of 2.5 yr (range 5 wk to 4.6 yr). Renal function significantly improved over a period of 12 months following conversion to tacrolimus (glomerular filtration rate 56 +/- 19 vs. 66 +/- 16 mL/min/1.73 m2; p < 0.03; n = 13). Fifteen of 20 (75%) patients tolerated tacrolimus well. The most frequent side-effects were neuropsychological and behavioral symptoms in three children, ranging from anorexia nervosa-like symptoms with weight loss, amenorrhea, depression and school problems to severe insomnia and to aggressive and anxious behavior in one child. Only the latter child was exposed to toxic tacrolimus blood levels. All side-effects were fully reversible after discontinuation of tacrolimus. In conclusion, tacrolimus had a beneficial effect on renal function and was well tolerated in the majority of pediatric patients. However, neuropsychologic and behavioral side-effects are important and maybe underrecognized in children. PMID:12709079

  5. Evolution of maternal effect senescence

    PubMed Central

    Moorad, Jacob A.; Nussey, Daniel H.

    2016-01-01

    Increased maternal age at reproduction is often associated with decreased offspring performance in numerous species of plants and animals (including humans). Current evolutionary theory considers such maternal effect senescence as part of a unified process of reproductive senescence, which is under identical age-specific selective pressures to fertility. We offer a novel theoretical perspective by combining William Hamilton’s evolutionary model for aging with a quantitative genetic model of indirect genetic effects. We demonstrate that fertility and maternal effect senescence are likely to experience different patterns of age-specific selection and thus can evolve to take divergent forms. Applied to neonatal survival, we find that selection for maternal effects is the product of age-specific fertility and Hamilton’s age-specific force of selection for fertility. Population genetic models show that senescence for these maternal effects can evolve in the absence of reproductive or actuarial senescence; this implies that maternal effect aging is a fundamentally distinct demographic manifestation of the evolution of aging. However, brief periods of increasingly beneficial maternal effects can evolve when fertility increases with age faster than cumulative survival declines. This is most likely to occur early in life. Our integration of theory provides a general framework with which to model, measure, and compare the evolutionary determinants of the social manifestations of aging. Extension of our maternal effects model to other ecological and social contexts could provide important insights into the drivers of the astonishing diversity of lifespans and aging patterns observed among species. PMID:26715745

  6. Evolution of maternal effect senescence.

    PubMed

    Moorad, Jacob A; Nussey, Daniel H

    2016-01-12

    Increased maternal age at reproduction is often associated with decreased offspring performance in numerous species of plants and animals (including humans). Current evolutionary theory considers such maternal effect senescence as part of a unified process of reproductive senescence, which is under identical age-specific selective pressures to fertility. We offer a novel theoretical perspective by combining William Hamilton's evolutionary model for aging with a quantitative genetic model of indirect genetic effects. We demonstrate that fertility and maternal effect senescence are likely to experience different patterns of age-specific selection and thus can evolve to take divergent forms. Applied to neonatal survival, we find that selection for maternal effects is the product of age-specific fertility and Hamilton's age-specific force of selection for fertility. Population genetic models show that senescence for these maternal effects can evolve in the absence of reproductive or actuarial senescence; this implies that maternal effect aging is a fundamentally distinct demographic manifestation of the evolution of aging. However, brief periods of increasingly beneficial maternal effects can evolve when fertility increases with age faster than cumulative survival declines. This is most likely to occur early in life. Our integration of theory provides a general framework with which to model, measure, and compare the evolutionary determinants of the social manifestations of aging. Extension of our maternal effects model to other ecological and social contexts could provide important insights into the drivers of the astonishing diversity of lifespans and aging patterns observed among species. PMID:26715745

  7. [Vascular and renal effects of anti-angiogenic therapy].

    PubMed

    Halimi, Jean-Michel; Azizi, Michel; Bobrie, Guillaume; Bouché, Olivier; Deray, Gilbert; des Guetz, Gaetan; Lecomte, Thierry; Levy, Bernard; Mourad, Jean-Jacques; Nochy, Dominique; Oudard, Stéphane; Rieu, Philippe; Sahali, Dil

    2008-12-01

    Angiogenesis inhibitor drugs (bevacizumab, sunitinib, sorafénib...) are now widely used for treatment of cancers, including colorectal, advanced renal cell and hepatocellular carcinomas, breast cancer). Vascular and renal side-effects of these drugs are not well known. Hypertension is one of the most common side effects. Incidence of hypertension may be different among angiogenis inhibitors and seems dose-depend. Arterial pressure can usually be controlled with anti-hypertensive medications, and treatment with angiogenesis inhibitors can be continued in most cases; however, serious hypertension-induced side effects were reported included malignant hypertension, stroke and reversible posterior leucoencephalopathy. Renal damage is infrequently reported: usually reversible mild or moderate proteinuria and in some rare cases nephritic syndrome, acute renal dysfunction, proliferative or collapsing glomerulonephritis, interstitial nephritis and thrombotic microangiopathy. Prolongation of the QT interval, congestive heart failure and left ventricular dysfunction have been reported in patients using tinibs. In the present guidelines, we recommend: (1) before the first administration of angiogenesis inhibitors: acute IV or oral antihypertensive medications should not be administered in a patient regardless of arterial pressure levels with postponing the administration because of hypertension is not recommended; (2) initial work-up should include ambulatory measurement of arterial pressure (by the general practitioner or by the patient using home blood pressure (three times in the morning and in the evening during three consecutive days) with a validated (cf: http://afssaps.sante.fr/) upper arm device: ideally, this device should be financed and provided by the pharmaceutical companies marketing the angiogenesis inhibitor drugs. Using 24-hour ambulatory blood pressure measurement is optional; (3) urine dipstick (and quantification if positive) and estimated glomerular

  8. Effect of Shock Wave Lithotripsy on Renal Hemodynamics

    NASA Astrophysics Data System (ADS)

    Handa, Rajash K.; Willis, Lynn R.; Evan, Andrew P.; Connors, Bret A.

    2008-09-01

    Extracorporeal shock wave lithotripsy (SWL) can injure tissue and decrease blood flow in the SWL-treated kidney, both tissue and functional effects being largely localized to the region targeted with shock waves (SWs). A novel method of limiting SWL-induced tissue injury is to employ the "protection" protocol, where the kidney is pretreated with low-energy SWs prior to the application of a standard clinical dose of high-energy SWs. Resistive index measurements of renal vascular resistance/impedance to blood flow during SWL treatment protocols revealed that a standard clinical dose of high-energy SWs did not alter RI during SW application. However, there was an interaction between low- and high-energy SWL treatment phases of the "protection" protocol such that an increase in RI (vasoconstriction) was observed during the later half of SW application, a time when tissue damage is occurring during the standard high-energy SWL protocol. We suggest that renal vasoconstriction may be responsible for reducing the degree of tissue damage that normally results from a standard clinical dose of high-energy SWs.

  9. Renal effects of Anchomanes difformis crude extract in wistar rats

    PubMed Central

    Ataman E, Jacob; Idu, MacDonald

    2015-01-01

    Objective: Anchomanes difformis is a member of the plant family Araceae which is used as a diuretic but also has other medicinal applications. This study investigates the dietary effects of A. difformis on the kidneys of adult wistar rats. Materials and Methods: Sixteen rats were used and were weighed, before and after the experiment. All rats were randomly divided into four groups. All groups were treated with the following regimen for two weeks. The control group (A) was fed on feed mash and water ad libitum throughout the period. The treatment groups B, C, and D received feed mash mixed with crude extract of A. difformis in the following proportions: 25:75(g), 50:50(g), and 75:25(g), respectively. The kidneys of the experimental animals were histologically examined for morphologic changes. Results: Results showed a significant difference (p<0.05) in the kidney weight of the treatment groups compared with the control. Histological examination of the renal tissues also showed considerable lesions such as inflammation, focal cortical and interstitial hemorrhage, and fibrosis in the treated rats compared with the control. Conclusion: The current study results suggest renal toxicity with excessive consumption of A.difformis. PMID:25767753

  10. Renal effect of YM435, a new dopamine D1 receptor agonist, in anesthetized dogs.

    PubMed

    Yatsu, T; Arai, Y; Takizawa, K; Kasai-Nakagawa, C; Takanashi, M; Uchida, W; Inagaki, O; Tanaka, A; Asano, M; Honda, K; Takenaka, T

    1997-03-12

    The renal effects of YM435 ((-)-(S)-4-(3,4-dihydroxyphenyl)-7,8-dihydroxy -1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate), a dopamine D1 receptor agonist, were investigated in anesthetized dogs. Intravenous infusion of YM435 (0.1-3 micrograms/kg per min) increased renal blood flow and decreased mean blood pressure in a dose-dependent manner with little effect on heart rate. Glomerular filtration rate, urine flow and urinary sodium excretion were concomitantly increased. The renal effect of YM435 by intravenous infusion at 0.3 microgram/kg per min was completely blocked by treatment with the selective dopamine D1 receptor antagonist SCH 23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazep ine hydrochloride). Furthermore, intravenous infusion of YM435 (0.3 microgram/kg per min) reversed the angiotensin II-induced decreases in renal blood flow, glomerular filtration rate, urine flow and urinary sodium excretion, and prevented the decrease in renal blood flow, glomerular filtration rate and urine flow induced by renal nerve stimulation and platelet-activating factor (PAF). These results suggest that intravenous administration of YM435 produces renal vasodilating and diuretic/natriuretic effects by stimulation of dopamine D1 receptors, and demonstrate that YM435 can inhibit angiotensin II-, renal nerve stimulation- and PAF-induced renal dysfunction. PMID:9088869

  11. Effect of renal insufficiency on stone recurrence in patients with urolithiasis.

    PubMed

    Kang, Ho Won; Seo, Sung Phil; Kim, Won Tae; Kim, Yong-June; Yun, Seok-Joong; Lee, Sang-Cheol; Kim, Wun-Jae

    2014-08-01

    The study was designed to assess the relationship between glomerular filtration rate (GFR) and urinary stone-forming constituents, and to assess the effect of renal insufficiency on stone recurrence risk in first stone formers (SF). Baseline serum creatinine levels were obtained, and renal insufficiency was defined as creatinine clearance ≤60 mL/min (Cockroft-Gault). This retrospective case-control study consists of 342 first SF; 171 SF with normal renal function were selected with 1:1 propensity scores matched to 171 SF with renal insufficiency. Urinary metabolic evaluation was compared to renal function. GFR was positively correlated with urinary calcium, uric acid, and citrate excretion. Subjects with renal insufficiency had significantly lower urinary calcium, uric acid, and citrate excretion than those with normal renal function, but not urine volume. With regard to urinary metabolic abnormalities, similar results were obtained. SF with renal insufficiency had lower calcium oxalate supersaturation indexes and stone recurrence rates than SF with normal renal function. Kaplan-Meier curves showed similar results. In conclusion, GFR correlates positively with urinary excretion of stone-forming constituents in SF. This finding implies that renal insufficiency is not a risk factor for stone recurrence. PMID:25120325

  12. Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model.

    PubMed

    Wang, Jian; Zhou, DA-Qing; He, Meng; Li, Wen-Gang; Pang, Xiang; Yu, Xiao-Xiang; Jiang, Bo

    2013-05-01

    The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as controls). Subsequently, a puncture biopsy was conducted on the kidneys at five pressure levels: 10, 20, 30, 40 and 50 mmHg. Once the renal pelvic pressure had increased, the healthy and injured kidneys presented pathological changes, including dilation of the renal tubule and capsule and compression of the renal glomerulus. When the renal pelvic pressure exceeded 20 mmHg, the injured kidney presented more damage. Electron microscopy revealed that the increase in pressure resulted in the following: the podocyte gap widened, the epithelial cells of the renal capsule separated from the basement membrane, the basement membrane thickness became uneven, the continuity of the basement membrane was interrupted at multiple positions and the renal tubule microvillus arrangement became disorganised. The manifestations in the pyonephrosis model were more distinct compared with those in the healthy kidney. As the renal pelvic pressure exceeds 20 mmHg under a renal purulent infection status, the nephrons become damaged. The extent of the damage is aggravated as the pressure is increased. PMID:23737886

  13. Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model

    PubMed Central

    WANG, JIAN; ZHOU, DA-QING; HE, MENG; LI, WEN-GANG; PANG, XIANG; YU, XIAO-XIANG; JIANG, BO

    2013-01-01

    The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as controls). Subsequently, a puncture biopsy was conducted on the kidneys at five pressure levels: 10, 20, 30, 40 and 50 mmHg. Once the renal pelvic pressure had increased, the healthy and injured kidneys presented pathological changes, including dilation of the renal tubule and capsule and compression of the renal glomerulus. When the renal pelvic pressure exceeded 20 mmHg, the injured kidney presented more damage. Electron microscopy revealed that the increase in pressure resulted in the following: the podocyte gap widened, the epithelial cells of the renal capsule separated from the basement membrane, the basement membrane thickness became uneven, the continuity of the basement membrane was interrupted at multiple positions and the renal tubule microvillus arrangement became disorganised. The manifestations in the pyonephrosis model were more distinct compared with those in the healthy kidney. As the renal pelvic pressure exceeds 20 mmHg under a renal purulent infection status, the nephrons become damaged. The extent of the damage is aggravated as the pressure is increased. PMID:23737886

  14. Effects of dopamine in the renal vascular bed of fetal, newborn, and adult sheep

    SciTech Connect

    Nakamura, K.T.; Felder, R.A.; Jose, P.A.; Robillard, J.E.

    1987-03-01

    The renal hemodynamic response to renal arterial dopamine infusions was compared in unanesthetized fetal, newborn, and adult sheep. Mean arterial blood pressure and heart rate remained unchanged during intrarenal dopamine infusions. Dopamine produced dose-related decreases in mean renal blood flow velocity in all three groups. When compared with adult sheep fetal sheep were slightly more sensitive to the vasoconstrictive effects of dopamine ED/sub 50/. Increases in mean renal blood flow velocity were not seen at any dose given until dopamine was infused during ..cap alpha..- and ..beta..-adrenoceptor blockade. The largest mean increase in renal flow velocity was 13 +/- 3, 16 +/- 3, and 17 +/- 4% in fetal, newborn, and adult sheep, respectively. cis-Flupentixol inhibited the vasodilation. Renal blood flow was measured using the radioactive microspheres techniques. This study demonstrates the presence of renal vasodilation following renal arterial dopamine infusions in fetal, newborn, and adult sheep when renal ..cap alpha..- and ..beta..-adrenoceptors are blocked. Vasodilator responses are similar in all three groups, and increases in renal blood flow velocity are small compared with that of other experimental models.

  15. Functional consequences of prenatal methylmercury exposure: effects on renal and hepatic responses to trophic stimuli and on renal excretory mechanisms

    SciTech Connect

    Slotkin, T.A.; Kavlock, R.J.; Cowdery, T.; Orband, L.; Bartolome, M.

    1986-01-01

    The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal activity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation of cellular maturation) and an eventual relative hypertrophy; liver ODC was reduced and hypertrophy was not evident. In contrast, the reactivity of liver ODC to trophic stimulants (vasopressin, isoproterenol) was markedly enhanced by prenatal methylmercury exposure, whereas renal ODC responses were much less affected (vasopressin) or actually reduced (isoproterenol). Targeted actions of methylmercury on renal excretory function were also prominent, with increased fractional excretions urea and electrolytes and an eventual reduction in glomerular filtration as assessed by creatinine clearance. These studies show that doses of methylmercury ordinarily associated with selective actions on development of neurobehavioral patterns also influence the functional ontogeny of other organ systems; furthermore, the fact that the target tissues are different for prenatal vs postnatal methylmercury exposure, indicates that the functional teratology of methylmercury exhibits critical periods of sensitivity.

  16. Antioxidant Effect of Erythropoietin during Experimental Chronic Renal Failure.

    PubMed

    Osikov, M V; Telesheva, L F; Ageev, Yu I

    2015-12-01

    The effects of erythropoietin (Epokrin, 900 U/kg) on the parameters of free radical oxidation in the plasma and lymphocytes of peripheral blood were studied in rats with chronic renal failure. We observed accumulation of primary (diene conjugates) and secondary (ketodienes, and conjugated trienes) LPO products in the heptane and isopropanol fractions of blood plasma and a decrease in superoxide dismutase and catalase activities in blood plasma. In lymphocytes, the concentration of primary, secondary and end-products (Schiff bases) of LPO increased in the isopropanol fraction of lipid extract. Treatment with erythropoietin was followed by a decrease in the level of primary and end-products of LPO in the isopropanol fraction of lipid extract of the plasma and lymphocytes and an increase in of superoxide dismutase and catalase activities in the plasma. The content of primary LPO products in the isopropanol fraction of the plasma progressively decreased with increasing superoxide dismutase and catalase activities in the plasma. PMID:26639466

  17. Evaluation of effect of impaired renal function on lamivudine pharmacokinetics

    PubMed Central

    Bouazza, Naïm; Tréluyer, Jean-Marc; Ghosn, Jade; Hirt, Déborah; Benaboud, Sihem; Foissac, Frantz; Viard, Jean-Paul; Urien, Saik

    2014-01-01

    Aims This study aimed to describe lamivudine pharmacokinetics in patients with impaired renal function and to evaluate the consistency of current dosing recommendations. Methods A total of 244 patients, ranging in age from 18 to 79 years (median 40 years) and in bodyweight from 38 to 117 kg (median 71 kg), with 344 lamivudine plasma concentrations, were analysed using a population pharmacokinetic analysis. Serum creatinine clearance (CLCR) was calculated using the Cockcroft–Gault formula; 177 patients had normal renal function (CLCR > 90 ml min−1), 50 patients had mild renal impairment (CLCR = 60–90 ml min−1), 20 patients had moderate renal impairment (CLCR = 30–60 ml min−1), and five patients had severe renal impairment (CLCR < 30 ml min−1). Results A two-compartment model adequately described the data. Typical population estimates (percentage interindividual variability) of the apparent clearance (CL/F), central (Vc/F) and peripheral volumes of distribution (Vp/F), intercompartmental clearance (Q/F) and absorption rate constant (Ka) were 29.7 l h−1 (32%), 68.2 l, 114 l, 10.1 l h−1 (85%) and 1 h−1, respectively. Clearance increased significantly and gradually with CLCR. Our simulations showed that a dose of 300 mg day−1 in patients with mild renal impairment could overexpose them. A dose of 200 mg day−1 maintained an exposure close to that of adults with normal renal function. However, the current US Food and Drug Administration recommendations for lamivudine in other categories of patients (from severe to moderate renal impairment) provided optimal exposures. Conclusions Lamivudine elimination clearance is related to renal function. To provide optimal exposure, patients with mild renal impairment should receive 200 mg day−1 instead of 300 mg day−1. PMID:24750102

  18. Renal and blood pressure effects from environmental cadmium exposure in Thai children

    SciTech Connect

    Swaddiwudhipong, Witaya; Mahasakpan, Pranee; Jeekeeree, Wanpen; Funkhiew, Thippawan; Sanjum, Rungaroon; Apiwatpaiboon, Thitikarn; Phopueng, Ittipol

    2015-01-15

    Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of β{sub 2}-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥1 μg/g creatinine. The prevalence of urinary cadmium ≥1 μg/g creatinine was significantly higher in girls and in those consuming rice grown in cadmium-contaminated areas. The geometric mean levels of urinary β{sub 2}-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary β{sub 2}-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children. - Highlights: • Few studies show renal effects from environmental cadmium exposure in children. • We report renal and blood pressure effects from cadmium exposure in Thai children. • Urinary β{sub 2}-microglobulin and calcium increased with increasing urinary cadmium. • The study found no association between urinary cadmium levels and blood pressure. • Environmental cadmium exposure can affect renal functions in children.

  19. Effect of chronic alcohol feeding on physiological and molecular parameters of renal thiamin transport

    PubMed Central

    Subramanian, Veedamali S.; Subramanya, Sandeep B.; Tsukamoto, Hidekazu

    2010-01-01

    The renal thiamin reabsorption process plays an important role in regulating thiamin body homeostasis and involves both thiamin transporters-1 and -2 (THTR1 and THTR2). Chronic alcohol use is associated with thiamin deficiency. Although a variety of factors contribute to the development of this deficiency, effects of chronic alcohol use on renal thiamin transport have not been thoroughly examined. We addressed this issue by examining the effect of chronic alcohol feeding of rats with liquid diet on physiological and molecular parameters of renal thiamin transport. Chronic alcohol feeding caused a significant inhibition in carrier-mediated thiamin transport across the renal brush-border membrane and was evident as early as 2 wk after initiation of alcohol feeding. Similarly, thiamin transport across the renal basolateral membrane was significantly inhibited by chronic alcohol feeding. The inhibition in renal thiamin transport was associated with a marked decrease in the level of expression of THTR1 and -2 proteins, mRNAs, and heterogeneous nuclear RNAs. Chronic alcohol feeding also caused a significant reduction in the level of expression of thiamin pyrophosphokinase but not that of the mitochondrial thiamin pyrophosphate transporter. These studies show that chronic alcohol feeding inhibits the entry and exit of thiamin in the polarized renal epithelial cells and that the effect is, at least in part, mediated at the transcriptional level. These findings also suggest that chronic alcohol feeding interferes with the normal homeostasis of thiamin in renal epithelial cells. PMID:20427470

  20. Acute effects of ferumoxytol on regulation of renal hemodynamics and oxygenation

    PubMed Central

    Cantow, Kathleen; Pohlmann, Andreas; Flemming, Bert; Ferrara, Fabienne; Waiczies, Sonia; Grosenick, Dirk; Niendorf, Thoralf; Seeliger, Erdmann

    2016-01-01

    The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). This study details the impact of ferumoxytol on regulation of renal hemodynamics and oxygenation. In 10 anesthetized rats, a single intravenous injection of isotonic saline (used as volume control) was followed by three consecutive injections of ferumoxytol to achieve cumulative doses of 6, 10, and 41 mg Fe/kg body mass. Arterial blood pressure, renal blood flow, renal cortical and medullary perfusion and oxygen tension were continuously measured. Regulation of renal hemodynamics and oxygenation was characterized by dedicated interventions: brief periods of suprarenal aortic occlusion, hypoxia, and hyperoxia. None of the three doses of ferumoxytol resulted in significant changes in any of the measured parameters as compared to saline. Ferumoxytol did not significantly alter regulation of renal hemodynamics and oxygenation as studied by aortic occlusion and hypoxia. The only significant effect of ferumoxytol at the highest dose was a blunting of the hyperoxia-induced increase in arterial pressure. Taken together, ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation. This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction. PMID:27436132

  1. Acute effects of ferumoxytol on regulation of renal hemodynamics and oxygenation.

    PubMed

    Cantow, Kathleen; Pohlmann, Andreas; Flemming, Bert; Ferrara, Fabienne; Waiczies, Sonia; Grosenick, Dirk; Niendorf, Thoralf; Seeliger, Erdmann

    2016-01-01

    The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). This study details the impact of ferumoxytol on regulation of renal hemodynamics and oxygenation. In 10 anesthetized rats, a single intravenous injection of isotonic saline (used as volume control) was followed by three consecutive injections of ferumoxytol to achieve cumulative doses of 6, 10, and 41 mg Fe/kg body mass. Arterial blood pressure, renal blood flow, renal cortical and medullary perfusion and oxygen tension were continuously measured. Regulation of renal hemodynamics and oxygenation was characterized by dedicated interventions: brief periods of suprarenal aortic occlusion, hypoxia, and hyperoxia. None of the three doses of ferumoxytol resulted in significant changes in any of the measured parameters as compared to saline. Ferumoxytol did not significantly alter regulation of renal hemodynamics and oxygenation as studied by aortic occlusion and hypoxia. The only significant effect of ferumoxytol at the highest dose was a blunting of the hyperoxia-induced increase in arterial pressure. Taken together, ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation. This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction. PMID:27436132

  2. Left renal vein transposition is effective for posterior nutcracker syndrome.

    PubMed

    Chen, Yuedong; Xing, Jinchun; Liu, Fei

    2014-01-01

    An 8-year-old girl was enrolled in hospital with intermittent gross hematuria in a period of 3 years. Bloody efflux from the left ureteral orifice was diagnosed in this patient with urethrocystoscopy. A retroaortic left renal vein appeared to be compressed by the aorta as detected by computerized tomography. The left renal vein was compressed between the aorta and the spine. A groove in the anterior surface of the left renal vein was detected. A transposition surgery of the left renal vein to a site in front of the aorta was performed for the patient. The patient was discharged after recovery and the hematuria symptom was not found during the 15-month follow-up investigation. PMID:25664135

  3. Effect of blood transfusions on canine renal allograft survival

    SciTech Connect

    van der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-04-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  4. Effect of blood transfusions on canine renal allograft survival

    SciTech Connect

    Van Der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-04-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Futhermore, no improvement in graft survival has been found after a peroperative transfuson of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion of irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  5. Ameliorative Effect of Recombinant Human Erythropoietin and Ischemic Preconditioning on Renal Ischemia Reperfusion Injury in Rats

    PubMed Central

    Elshiekh, Mohammed; Kadkhodaee, Mehri; Seifi, Behjat; Ranjbaran, Mina; Ahghari, Parisa

    2015-01-01

    Background: Ischemia-reperfusion (IR) injury is one of the most common causes of renal dysfunction. There is increasing evidence about the role of the reactive oxygen species (ROS) in these injuries and endogenous antioxidants seem to have an important role in decreasing the renal tissue injury. Objectives: The aim of this study was to compare the effect of recombinant human erythropoietin (EPO) and ischemic preconditioning (IPC) on renal IR injury. Materials and Methods: Twenty four male Wistar rats were allocated into four experimental groups: sham-operated, IR, EPO + IR, and IPC + IR. Rats were underwent 50 minutes bilateral ischemia followed by 24 hours reperfusion. Erythropoietin (5000 IU/kg, i.p) was administered 30 minutes before onset of ischemia. Ischemic preconditioning was performed by three cycles of 3 minutes ischemia followed by 3 minutes reperfusion. Plasma concentrations of urea and creatinine were measured. Kidney samples were taken for reactive oxidative species (ROS) measurement including superoxide dismutase (SOD) activity, glutathione (GSH) contents, and malondialdehyde (MDA) levels. Results: Compared to the sham group, IR led to renal dysfunction as evidenced by significantly higher plasma urea and creatinine. Treatment with EPO or IPC decreased urea, creatinine, and renal MDA levels and increased SOD activity and GSH contents in the kidney. Conclusions: Pretreatment with EPO and application of IPC significantly ameliorated the renal injury induced by bilateral renal IR. However, both treatments attenuated renal dysfunction and oxidative stress in kidney tissues. There were no significant differences between pretreatment with EPO or application of IPC. PMID:26866008

  6. Acceptance and effects of a therapeutic renal food in pet cats with chronic kidney disease

    PubMed Central

    Fritsch, Dale A; Jewell, Dennis E

    2015-01-01

    Introduction Renal foods are used to manage chronic kidney disease (CKD) in dogs and cats, but their effectiveness may be limited by the ability to transition animals to them. Material and Methods In a prospective study, pet cats with previously undiagnosed kidney disease (20 International Renal Interest Society (IRIS) 1, 61 IRIS 2, 14 IRIS 3/4, 33 at risk for CKD) were transitioned to a renal food. Markers of renal function were measured and owners answered questionnaires about their pet over one year. Results All but eight cats (120/128; 94 per cent) successfully transitioned to the renal food. Most of the time, cats moderately or extremely liked the food (89 per cent), ate at least half (73 per cent) and were moderately or extremely enthusiastic while eating (68 per cent). Cats rarely disliked the food (2 per cent) or refused to eat it (1 per cent). Markers of renal function were unchanged in IRIS 1 and 2 cats and changed little in IRIS 3/4 cats. In all groups, owner-assessed quality of life improved initially and then remained stable. Mean bodyweight did not change in cats with CKD. Conclusions Most cats with CKD successfully transitioned to the renal food. The results also support previous studies that the renal food can help stabilise cats with CKD. PMID:26587240

  7. Effects of aging and uninephrectomy on renal changes in Tsukuba hypertensive mice

    PubMed Central

    INUI, YOSUKE; MOCHIDA, HIDEKI; YAMAIRI, FUMIKO; OKADA, MIYOKO; ISHIDA, JUNJI; FUKAMIZU, AKIYOSHI; ARAKAWA, KENJI

    2013-01-01

    Renal dysfunction is accelerated by various factors such as hypertension, aging and diabetes. Glomerular hyper-filtration, considered one of the major risk factors leading to diabetic nephropathy, is often encountered in diabetic patients. However, the interrelationship of these risk factors during the course and development of renal dysfunction has not been fully elucidated. In this study, the effects of aging and uninephrectomy (UNx)-induced hyperfiltration on renal changes were investigated in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. In THM, the urinary albumin/creatinine (Alb/Cr) ratio was elevated with age without a concomitant increase in the plasma Cr concentration. Moreover, the urinary neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr) ratio, the renal monocyte chemoattractant protein-1 (MCP-1) mRNA expression and the renal collagen type I α 2 (COL1A2) mRNA expression were also increased with age. Age-related albuminuria in THM is likely caused by renal tubular damage, enhanced inflammatory response and tubulointerstitial fibrosis. Furthermore, following UNx, the urinary Alb/Cr ratio and the plasma Cr concentration were increased in THM. The urinary NGAL/Cr ratio and the renal MCP-1 and COL1A2 mRNA expression were not affected by UNx. These results suggested that UNx-induced albuminuria in THM was caused by glomerular dysfunction, rather than renal tubular injury. In conclusion, this study demonstrated for the first time the effects of aging and UNx on renal changes in THM. These findings strongly reinforce the significance of applying a diversity of therapeutic approaches to the management of renal dysfunction. PMID:24648949

  8. Effects of Renal Denervation Documented in the Austrian National Multicentre Renal Denervation Registry

    PubMed Central

    Lambert, Thomas; Steinwender, Clemens; Weber, Thomas; Suppan, Markus; Brussee, Helmut; Koppelstätter, Christian; Kerschbaum, Julia; Watschinger, Bruno; Hohenstein-Scheibenecker, Katharina; Reindl-Schwaighofer, Roman; Sturmberger, Thomas; Kindslehner, Claudia; Weiss, Thomas Werner; Rohla, Miklos; Gruener, Peter; Maister, Petra; Auer, Johann; Dechant, Cornelia; Sykora, Josef; Krismer, Christoph; Glaser, Stefan; Zweiker, Robert

    2016-01-01

    Renal denervation (RDN) is a new procedure for treatment-resistant hypertensive patients. In order to monitor all procedures undergone in Austria, the Austrian Society of Hypertension established the investigator-initiated Austrian Transcatheter Renal Denervation (TREND) Registry. From April 2011 to September 2014, 407 procedures in 14 Austrian centres were recorded. At baseline, office and mean 24-h ambulatory blood pressure (ABP) were 171/94 and 151/89 mmHg, respectively, and patients were taking a median of 4 antihypertensive medications. Mean 24-h ABP changes after 2–6 weeks, 3, 6 and 12 months were -11/-6, -8/-4, -8/-5 and -10/-6 mmHg (p<0.05 at all measurements), respectively. The periprocedural complication rate was 2.5%. Incidence of long-term complications during follow-up (median 1 year) was 0.5%. Office BP and ABP responses showed only a weak correlation (Pearson coefficient 0.303). Based on the data from the TREND registry, ambulatory blood pressure monitoring in addition to office BP should be used for patient selection as well as for monitoring response to RDN. Furthermore, criteria for optimal patient selection are suggested. PMID:27529426

  9. Effects of Renal Denervation Documented in the Austrian National Multicentre Renal Denervation Registry.

    PubMed

    Zweiker, David; Lambert, Thomas; Steinwender, Clemens; Weber, Thomas; Suppan, Markus; Brussee, Helmut; Koppelstätter, Christian; Kerschbaum, Julia; Watschinger, Bruno; Hohenstein-Scheibenecker, Katharina; Reindl-Schwaighofer, Roman; Sturmberger, Thomas; Kindslehner, Claudia; Weiss, Thomas Werner; Rohla, Miklos; Gruener, Peter; Maister, Petra; Auer, Johann; Dechant, Cornelia; Sykora, Josef; Krismer, Christoph; Glaser, Stefan; Zweiker, Robert

    2016-01-01

    Renal denervation (RDN) is a new procedure for treatment-resistant hypertensive patients. In order to monitor all procedures undergone in Austria, the Austrian Society of Hypertension established the investigator-initiated Austrian Transcatheter Renal Denervation (TREND) Registry. From April 2011 to September 2014, 407 procedures in 14 Austrian centres were recorded. At baseline, office and mean 24-h ambulatory blood pressure (ABP) were 171/94 and 151/89 mmHg, respectively, and patients were taking a median of 4 antihypertensive medications. Mean 24-h ABP changes after 2-6 weeks, 3, 6 and 12 months were -11/-6, -8/-4, -8/-5 and -10/-6 mmHg (p<0.05 at all measurements), respectively. The periprocedural complication rate was 2.5%. Incidence of long-term complications during follow-up (median 1 year) was 0.5%. Office BP and ABP responses showed only a weak correlation (Pearson coefficient 0.303). Based on the data from the TREND registry, ambulatory blood pressure monitoring in addition to office BP should be used for patient selection as well as for monitoring response to RDN. Furthermore, criteria for optimal patient selection are suggested. PMID:27529426

  10. Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo.

    PubMed

    Reichman, J; Cohen, S; Goldfarb, M; Shina, A; Rosen, S; Brezis, M; Karmeli, F; Heyman, S N

    2001-01-01

    The constitutive cyclooxygenase (COX)-1 enzyme has been considered the physiologically important isoform for prostaglandin synthesis in the normal kidney. It has, therefore, been suggested that selective inhibitors of the 'inducible' isoform (COX-2) may be free from renal adverse effects. We studied the renal effects of the predominantly COX-2 antagonist nabumetone in isolated perfused kidneys. As compared with controls, kidneys removed after in vivo administration of oral nabumetone (15 mg/kg) disclosed altered renal function with reduced glomerular filtration rate, filtration fraction, and urine volume and enhanced hypoxic outer medullary tubular damage. By contrast, renal function and morphology were not affected in vivo by nabumetone or its active metabolite 6-methoxy-2-naphthylacetic acid. The latter agent (10-20 mg/kg i.v.) did not significantly alter renal microcirculation, as opposed to a selective substantial reduction in medullary blood flow noted with the nonselective COX inhibitor indomethacin (5 mg/kg i.v.). In a rat model of acute renal failure, induced by concomitant administration of radiocontrast, nitric oxide synthase, and COX inhibitors, the decline in kidney function and the extent of hypoxic medullary damage with oral nabumetone (80 mg/kg) were comparable to a control group, and significantly less than those induced by indomethacin. In rats subjected to daily oral nabumetone for 3 consecutive weeks, renal function and morphology were preserved as well. Both nabumetone and 6-methoxy-2-naphthylacetic acid reduced renal parenchymal prostaglandin E2 to the same extent as indomethacin. It is concluded that while nabumetone adversely affects renal function and may intensify hypoxic medullary damage ex vivo, rat kidneys are not affected by this agent in vivo, both in acute and chronic studies. COX selectivity may not explain the renal safety of nabumetone. PMID:11701998

  11. Effect of Renal Function on Prognosis in Chronic Heart Failure

    PubMed Central

    Löffler, Adrián I.; Cappola, Thomas P.; Fang, James; Hetzel, Scott J.; Kadlec, Andrew; Astor, Brad; Sweitzer, Nancy K.

    2014-01-01

    Renal dysfunction (RD) is associated with increased mortality in heart failure (HF). The aim of this study was to identify whether worsened or improved renal function during mid-term follow-up is associated with worsened outcomes in chronic HF patients. 892 participants from a multicenter cohort study of chronic HF were followed over 3.1±1.9 years of enrollment. Worsened and improved renal function were tested with multivariable models as independent predictors of HF hospitalization and mortality. While 12% of subjects experienced a ≥25% decrease in estimated glomerular filtration rate (eGFR), 17% experienced a ≥25% increase in eGFR, and there was stability of kidney function observed in the cohort as a whole. The quartile with the worst RD at any point in time had increased risk of HF hospitalization and mortality. Worsened eGFR was associated with HF outcomes in the unadjusted (HR=1.71 (95%CI 1.04-2.81), p=0.035), but not the adjusted analysis. Improvement in eGFR was not associated with outcome (p=0.453). In chronic HF, the severity of RD predicts risk of poor outcome better than changes in renal function during mid-term follow-up. This suggests that in patients with appropriately treated chronic HF, worsening renal function in itself does not yield useful prognostic information and may not reflect poor outcome. PMID:25465925

  12. Renal handling of cadmium in perfused rat kidney and effects on renal function and tissue composition.

    PubMed

    Diamond, G L; Cohen, J J; Weinstein, S L

    1986-11-01

    Isolated rat kidneys perfused with a Krebs-Ringer bicarbonate (KRB) solution containing 1 microM CdCl2 plus 6% substrate-free albumin (SFA) and a mixture of substrates accumulated substantially less cadmium in tissue than kidneys perfused with 1 microM CdCl2 in a protein-free KRB solution containing the same substrates: 11 vs. 205 nmol Cd/g dry wt. Decreasing the glomerular filtration rate (GFR) by occluding the ureters of kidneys perfused in the absence of albumin did not change the rate of net tissue uptake of cadmium (Cd), suggesting that the kidney can extract Cd from the peritubular capillary fluid and that net uptake of Cd is not dependent on the reabsorption of filtered Cd. The tissue accumulation of large quantities of Cd (1.8 mumol Cd/g dry wt), which established levels of non-metallothionein-bound Cd exceeding 1 mumol Cd/g dry wt, caused no changes in either GFR, perfusion flow rate, fractional reabsorption of Na+, fractional reabsorption of K+, fractional reabsorption of glucose, or free-water clearance. However, discrete changes in renal tissue K+ content were observed. Exposure to 1 microM CdCl2 resulted in a net loss of renal tissue K+ in rat kidneys perfused with substrate-enriched KRB containing 6% albumin. Exposure to 0.8 microM or 7 microM CdCl2 completely prevented K+ loss from kidneys perfused with a substrate-enriched, protein-free KRB solution. PMID:3777178

  13. Effects of Sugammadex and Neostigmine on Renal Biomarkers

    PubMed Central

    Isik, Yasemin; Palabiyik, Onur; Cegin, Bilal Muhammed; Goktas, Ugur; Kati, Ismail

    2016-01-01

    Background Neostigmine, the currently commonly used agent for reversal of neuromuscular blockade. Sugammadex is a novel and unique compound designed as an antagonist of steroidal neuromuscular blockers. In this study, we evaluated the effects of sugammadex or neostigmine on kidney functions in patients scheduled for elective surgery. Material/Methods Patients scheduled for a surgical procedure under desflurane/opioid anesthesia received an intubating dose rocuronium. Patients were divided into 2 groups receiving either sugammadex or neostigmine atropine to reverse neuromuscular blockade. Cystatin C, creatinine, urea, blood urea nitrogen, sodium, potassium, and calcium levels in the blood and α1microglobulin, β2microglobulin, and microalbumin levels in the urine were measured. Results There was no significant difference between the groups with regard to the demographic data. In the Neostigmine Group, although β2microglobulin and microalbumin were similar, a significant increase was found in the postoperative α1microglobulin and cystatin C values. In the Sugammadex Group, although β2-microglobulin and cystatin C were similar, a significant increase was found in the postoperative α1-microglobulin and microalbumin values. The only significant difference was cystatin C value variation in the Neostigmine Group compared to the Sugammadex Group. Conclusions We believe that the use of more specific and sensitive new-generation markers like cystatin C to evaluate kidney function will provide a better understanding and interpretation of our results. Sugammadex has more tolerable effects on kidney function in patients than does neostigmine. However, when compared to preoperative values, there is a negative alteration of postoperative values. Neostigmine and sugammadex do not cause renal failure but they may affect kidney function. PMID:26963316

  14. [Effect of environmental and individual factors in renal lithiasis].

    PubMed

    Vasilescu, L; Ciochină, Al D; Corciovă, C

    2011-01-01

    The large number of cases with renal lithiasis occurring in the population of the south-east region of Iasi county has determined us to make a study in this region for the identification of environmental and individual factors involved in the etiopathogenesis of this disease. This study is performed to assert the corelation between the clinical and paraclinical patients data with those obtained through water and soil chemical analisys for identification of determinant environmental and individual factors involved in etiopathogenesis of this disease. This study indicates that the environment factors (water, soil) correlated with personal factors, especially the diet and standard of living are the favouring factors of renal lithiasis. PMID:21688574

  15. Renal sympathetic baroreflex effects of angiotensin II infusions into the rostral ventrolateral medulla of the rabbit.

    PubMed

    Saigusa, T; Head, G A

    1993-05-01

    1. The effects of local infusion of angiotensin II (AII) into the rostral ventrolateral medulla (RVLM) pressor area on the renal sympathetic baroreflex were compared with the excitatory amino acid glutamate in urethane anaesthetized rabbits with chronically implanted renal nerve electrodes. Baroreflex blood pressure-renal nerve activity curves were obtained by intravenous infusion of phenylephrine and nitroprusside before and after treatments. 2. Infusion of 4 pmol/min of AII into the RVLM increased blood pressure by 12 +/- 2 mmHg and transiently increased resting sympathetic nerve activity. The renal sympathetic baroreflex curves were shifted to the right. The upper plateau of the sympathetic reflex increased by 29 +/- 8% (n = 6, P < 0.025). 3. Infusions of glutamate into the RVLM, at a dose which was equipressor to that of AII, also increased resting renal sympathetic nerve activity. In contrast to AII, this increase was maintained throughout the infusion. Glutamate shifted the reflex curve to the right and increased the upper plateau of the sympathetic reflex by 44 +/- 5% without affecting the lower plateau. 4. These results support the suggestion that AII can act at the level of the RVLM pressor area to facilitate baroreflex control of renal sympathetic activity in a similar fashion to that produced by fourth ventricular administration. 5. Thus the RVLM is a likely candidate site for modulation of the renal sympathetic baroreflex. The similarity of the actions of AII to those of glutamate suggest that it may directly excite sympathetic vasomotor cells in this region. PMID:8100748

  16. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

    SciTech Connect

    Spino, M.; Chai, R.P.; Isles, A.F.; Balfe, J.W.; Brown, R.G.; Thiessen, J.J.; MacLeod, S.M.

    1985-07-01

    A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and /sup 125/I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion.

  17. Effects of central administration of morphine on renal function in conscious rats.

    PubMed

    Danesh, S; Walker, L A

    1988-02-01

    Systemic administration of morphine in rats produces an anti-natriuretic effect that is at least partially dependent on renal nerves. The present studies were carried out in order to assess the renal response to central administration of morphine. Male Sprague-Dawley rats were surgically prepared with arterial, venous and bladder cannulas. In addition, a guide cannula was placed into the lateral ventrical and secured to the surface of the skull. Experiments were carried out at least 3 days after surgery. Renal clearance measurements were 30 min each. After a basal period, morphine sulfate (4 micrograms/4 microliters) or vehicle was injected into the lateral cerebral ventricle. Two clearance measurements were obtained, followed by central administration of naloxone HCl (4 micrograms/4 microliters) or vehicle and two more clearance periods. Morphine administration had no effect on blood pressure or heart rate but caused a sharp reduction in sodium excretion (3200 +/- 958 vs 970 +/- 158 nEq/100 g/min in period 5; P less than .05). This response was reversed by the addition of naloxone (3280 +/- 583 nEq/100 g/min in period 5; P less than .05). Furthermore, morphine had no effect on renal plasma flow and glomerular filtration rate. Naloxone increased the renal plasma flow and glomerular filtration rate in morphine-treated rats, whereas it had no effect in controls. It is concluded that central administration of morphine in conscious rats enhances renal tubular sodium reabsorption by an opiate receptor-dependent mechanism. PMID:3346840

  18. The effect of 5-aminosalicylic acid on renal ischemia-reperfusion injury in rats

    PubMed Central

    Banaei, Shokofeh

    2016-01-01

    Objectives: Ischemia-reperfusion (IR) contributes to the development acute renal failure. Oxygen free radicals are involved in the pathophysiology of IR injury (IRI). This study was designed to investigate the effects of 5-aminosalicylic acid (5-ASA), which is known antioxidant agent, in IR-induced renal injury in rats. Materials and Methods: Male Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h of reperfusion. 5-ASA (300 mg/kg, i.p) was administered prior to ischemia. After 24 h reperfusion, urine and blood samples were collected for the determination of creatinine (Cr) and nitric oxide (NO) levels, and renal samples were taken for the histological evaluation. Results: Treatment with 5-ASA significantly decreased serum Cr and NO levels, also significantly increased urinary Cr level and decreased histopathological changes induced by IR. Conclusion: Treatment with 5-ASA had a beneficial effect on renal IRI. These results may indicate that 5-ASA exerts nephroprotective effects in renal IRI. PMID:27127324

  19. The Protective Effect of Melittin on Renal Fibrosis in an Animal Model of Unilateral Ureteral Obstruction.

    PubMed

    An, Hyun-Jin; Kim, Jung-Yeon; Kim, Woon-Hae; Han, Sang-Mi; Park, Kwan-Kyu

    2016-01-01

    Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease. Melittin is a major component of bee venom, and it has anti-bacterial, anti-viral, and anti-inflammatory properties in various cell types. Thus, this study examined the therapeutic effects of melittin on the progression of renal fibrosis using the unilateral ureteral obstruction (UUO) model. In addition, the effects of melittin on inflammation and fibrosis in renal fibroblast cells were explored using transforming growth factor-β1 (TGF-β1). Histological observation revealed that UUO induced a considerable increase in the number of infiltrated inflammatory cells. However, melittin treatment markedly reduced these reactions compared with untreated UUO mice. The expression levels of inflammatory cytokines and pro-fibrotic genes were significantly reduced in melittin-treated mice compared with UUO mice. Melittin also effectively inhibited fibrosis-related gene expression in renal fibroblasts NRK-49F cells. These findings suggest that melittin attenuates renal fibrosis and reduces inflammatory responses by the suppression of multiple growth factor-mediated pro-fibrotic genes. In conclusion, melittin may be a useful therapeutic agent for the prevention of fibrosis that characterizes the progression of chronic kidney disease. PMID:27618890

  20. Naloxone inhibits renal hemodynamic effect of head-out water immersion in humans.

    PubMed

    Van Tilborg, K A; Rabelink, T J; Koomans, H A

    1995-09-01

    Head-out water immersion (HOI) is followed by renal vasodilation and natriuresis, in association with a fall in blood pressure. The latter suggests an exaggerated sympathetic suppression. We studied the role of endogenous opioids on the renal response to HOI. Six healthy subjects underwent four- hour clearance studies during: (1) time control; (2) naloxone 0.1 mg/kg i.v. bolus, followed by 0.1 mg/kg/hr; (3) HOI; and (4) concomitant HOI and naloxone administration. Compared to the time control study, naloxone had no effects on mean arterial pressure (MAP), plasma renin activity (PRA), aldosterone, catecholamines, atrial natriuretic peptide (ANP), glomerular filtration rate (GFR), estimated renal plasma flow (ERPF), and sodium excretion. HOI caused significant decrements of MAP, PRA, aldosterone, and catecholamines, and increased ANP, GFR, from 94 +/- 5 to 102 +/- 5 ml/min (P < 0.01), ERPF, from 529 +/- 30 to 616 +/- 35 ml/min (P < 0.01), and sodium excretion. Renal blood flow increased as well, and calculated renal vascular resistance decreased from 99 +/- 6 to 77 +/- 5 mm Hg.min.liter-1 (P < 0.01). HOI during concomitant naloxone administration had similar effects on MAP and humoral factors, however, caused no change in GFR, ERPF and renal blood flow, and the fall in renal vascular resistance, from 98 +/- 6 to 83 +/- 5 mm Hg.min.liter-1 (P < 0.05) was significantly less than found in the absence of naloxone (P < 0.05). The natriuretic effect was undisturbed. These data suggest that endogenous opioids play a role in the response to HOI, in particular, potentiate the renal vasodilatory response. PMID:7474676

  1. Calcium oxalate nephrolithiasis: effect of renal crystal deposition on the cellular composition of the renal interstitium.

    PubMed

    de Water, R; Noordermeer, C; van der Kwast, T H; Nizze, H; Boevé, E R; Kok, D J; Schröder, F H

    1999-04-01

    Urinary calcium oxalate (CaOx) crystals and crystal agglomerates are normally harmlessly excreted, but in nephrolithiasis they are retained by tubular epithelial cells and shifted into the renal interstitium. This crystalline material induces an inflammatory response consisting of an increase in the number of interstitial cells and an expansion of the extracellular matrix. The newly arrived cells either derive from the blood or the connective tissue or they are formed by local proliferation. Identification of the cells that surround the interstitial crystals is a first step in investigating the question of whether the interstitial cells could remove the crystalline material. Therefore, we performed an immunohistochemical study on the kidneys of rats made hyperoxaluric by ethylene glycol (EG) and ammonium chloride (AC). Attention was paid to expression of the leukocyte common antigen (LCA), which identifies all types of leukocytes, the ED1 antigen, which is specific for monocytes and macrophages, and the major histocompatibility class II antigen (MHC II), which is present on dendritic cells, B lymphocytes, and activated macrophages. The results obtained were compared with those seen in two human kidney specimens with acute and chronic oxalosis. In both rat and humans, macrophages and multinucleated giant cells are the major cells that encapsulate the interstitial crystals. This similarity in response underlines the relevance of the rat nephrolithiasis model. The rat experiments showed, furthermore, that the number of interstitial crystals and the amount of biochemically measured kidney-associated oxalate both decrease with time, if the nephrolithiatic agents EG and AC are omitted from the drinking water. Further studies must clarify whether macrophages and multinucleated giant cells are able to remove the interstitial crystals and how these cells are recruited at the inflammatory site. PMID:10196021

  2. Renal effects of environmental and occupational lead exposure.

    PubMed Central

    Loghman-Adham, M

    1997-01-01

    Environmental and industrial lead exposures continue to pose major public health problems in children and in adults. Acute exposure to high concentrations of lead can result in proximal tubular damage with characteristic histologic features and manifested by glycosuria and aminoaciduria. Chronic occupational exposure to lead, or consumption of illicit alcohol adulterated with lead, has also been linked to a high incidence of renal dysfunction, which is characterized by glomerular and tubulointerstitial changes resulting in chronic renal failure, hypertension, hyperuricemia, and gout. A high incidence of nephropathy was reported during the early part of this century from Queensland, Australia, in persons with a history of childhood lead poisoning. No such sequela has been found in studies of three cohorts of lead-poisoned children from the United States. Studies in individuals with low-level lead exposure have shown a correlation between blood lead levels and serum creatinine or creatinine clearance. Chronic low-level exposure to lead is also associated with increased urinary excretion of low molecular weight proteins and lysosomal enzymes. The relationship between renal dysfunction detected by these sensitive tests and the future development of chronic renal disease remains uncertain. Epidemiologic studies have shown an association between blood lead levels and blood pressure, and hypertension is a cardinal feature of lead nephropathy. Evidence for increased body lead burden is a prerequisite for the diagnosis of lead nephropathy. Blood lead levels are a poor indicator of body lead burden and reflect recent exposure. The EDTA lead mobilization test has been used extensively in the past to assess body lead burden. It is now replaced by the less invasive in vivo X-ray fluorescence for determination of bone lead content. Images p928-a Figure 1. Figure 2. Figure 2. Figure 3. PMID:9300927

  3. Short-Term Effects of Ankaferd Hemostat for Renal Artery Embolization: An Experimental Study

    SciTech Connect

    Ozbek, Orhan; Acar, Kadir; Koc, Osman; Saritas, Kadir; Toy, Hatice; Solak, Yalcin; Ozbek, Seda; Kucukapan, Ahmet; Guler, Ibrahim; Gaipov, Abduzhappar; Turk, Suleyman; Haznedaroglu, Ibrahim Celaleddin

    2013-04-15

    Renal artery embolization (RAE) is a minimally invasive therapeutic technique that is utilized in a number of disorders. Ankaferd is a novel hemostatic agent with a new mechanism of action independent of clotting factors. We used Ankaferd for RAE in a sheep model. Seven adult female sheep were included in the study. Selective renal arteriogram using 5-F diagnostic catheter was performed to make sure that each kidney was fed by a single renal artery and the animal had normal renal vasculature. Coaxial 2.7-F microcatheter was advanced to the distal main renal artery. Under fluoroscopic guidance, 2 mL of Ankaferd mixed with 2 mL of nonionic iodinated contrast agent was slowly injected. Fluoroscopy was used to observe the deceleration of flow and stagnation. Control renal angiograms were performed just after embolization. After the procedure, the animals were observed for 1 day and then sacrificed with intravenous sodium thiopental. The technical success was observed in seven of the seven animals.. After embolization procedure, none of the animals died or experienced a major systemic adverse event. On macroscopic examination of the embolized kidneys, thrombus at the level of main renal artery formed after Ankaferd embolization was more compact compared with the thrombi that was not Ankaferd-associated, which was observed elsewhere. Microscopically, majority of the renal tubular cells (80-90 %) were necrotic, and there was epithelial cell damage in a small portion of the cells (10-20 %). RAE was safe and effective in the short-term with Ankaferd in studied animals. Further studies should be conducted to better delineate the embolizing potential of this novel hemostatic agent.

  4. Clinical evolution of chronic renal patients with HIV infection in replacement therapy.

    PubMed

    Saracho, Ramón; Martín Escobar, Eduardo; Comas Farnés, Jordi; Arcos, Emma; Mazuecos Blanca, Auxiliadora; Gentil Govantes, Miguel Ángel; Castro de la Nuez, Pablo; Zurriaga, Óscar; Ferrer Alamar, Manuel; Bouzas Caamaño, Encarnación; García Falcón, Teresa; Portolés Pérez, José; Herrero Calvo, José A; Chamorro Jambrina, Carlos; Moina Eguren, Íñigo; Rodrigo de Tomás, María Teresa; Abad Díez, José María; Sánchez Miret, José I; Alvarez Lipe, Rafael; Díaz Tejeiro, Rafael; Moreno Alía, Inmaculada; Torres Guinea, Marta; Huarte Loza, Enma; Artamendi Larrañaga, Marta; Fernández Renedo, Carlos; González Fernández, Raquel; Sánchez Álvarez, Emilio; Alonso de la Torre, Ramón

    2015-01-01

    Patients on renal replacement therapy (RRT) infected with the human immunodeficiency virus (HIV) are a special group with growing interest. In order to study the epidemiological data of HIV+ patients on RRT in Spain, we collected individual information from 2004-2011 (period of use of highly active antiretroviral therapy [HAART] in the Autonomous Communities of Andalusia, Aragon, Asturias, Catalonia, Valencia, Castilla la Mancha, Castilla León, Galicia, Madrid, La Rioja and the Basque Country, comprising 85% of the Spanish population. A total of 271 incident and 209 prevalent patients were analysed. They were compared with the remaining patients on RRT during the same period. The annual incidence was 0.8 patients per one million inhabitants, with a significant increase during the follow-up period. The proportion of prevalent HIV+ patients was 5.1 per 1,000 patients on RRT (95% confidence interval [CI] 4.4-5.8. Although glomerular diseases constituted the majority of cases (42%), diabetic nephropathy was the cause in 14% of patients. The nation-wide totals for these percentages were 13 and 25%, respectively. Compared to the total of patients in treatment, the risk of death was significantly higher in the HIV+ group: hazard ratio (HR) adjusted for age, sex and diabetes was 2.26 (95% CI 1.74 - 2.91). Hepatitis C coinfection increased the risk of death in the HIV+ group (HR 1.77; 95% CI 1.10 - 2.85). The probability of kidney transplantation in HIV+ was only 17% after 7 years, comparing with total RTT patients (HR 0.15; 95% CI: 0.10-0.24). Despite the use of HAART, the incidence of HIV+ patients on dialysis has increased; their mortality still exceeds non-HIV patients, and they have a very low rate of transplantation. It is necessary to further our knowledge of this disease in order to improve results. PMID:26409500

  5. Item Feature Effects in Evolution Assessment

    ERIC Educational Resources Information Center

    Nehm, Ross H.; Ha, Minsu

    2011-01-01

    Despite concerted efforts by science educators to understand patterns of evolutionary reasoning in science students and teachers, the vast majority of evolution education studies have failed to carefully consider or control for item feature effects in knowledge measurement. Our study explores whether robust contextualization patterns emerge within…

  6. Acute toxic effects of sustained-release verapamil in chronic renal failure.

    PubMed

    Pritza, D R; Bierman, M H; Hammeke, M D

    1991-10-01

    Four hypertensive patients with chronic renal insufficiency or end-stage renal disease who were treated with sustained-release verapamil hydrochloride subsequently developed acute toxic effects. All four patients developed varying degrees of atrioventricular heart block, hypotension, hyperkalemia, metabolic acidosis, and hepatic dysfunction. Supportive treatment consisted of intravenous catecholamines, sodium polystyrene sulfonate, and dialysis, and all patients recovered completely without any residual hepatic or cardiac disease. Patients with renal impairment who are treated with sustained-release verapamil may accumulate verapamil or its metabolites and develop toxic side effects. We conclude that sustained-release verapamil should be used with caution in this patient population and that patients should be closely monitored for adverse cardiovascular, metabolic, and hepatic side effects. PMID:1843183

  7. Renovascular effects of nonprescription ibuprofen in elderly hypertensive patients with mild renal impairment.

    PubMed

    Furey, S A; Vargas, R; McMahon, F G

    1993-01-01

    To determine the renovascular effects of nonprescription ibuprofen in the maximum labeled over-the-counter (OTC) dosage for 7 days, and to compare these effects with those of two other available OTC analgesics, aspirin and acetaminophen, we evaluated 25 elderly patients with mild thiazide-treated hypertension and mild renal insufficiency. Under double-blind conditions, patients were randomly allocated to one of three treatment groups: ibuprofen 400 mg 3 times/day, aspirin 650 mg 3 times/day, or acetaminophen 650 mg 3 times/day. Blood pressure and indexes of renal function (blood urea nitrogen, creatinine clearance, serum electrolytes) were measured over 7 days in a clinical research center. None of the treatments had a clinically significant effect on blood pressure. Renal function indexes also remained unchanged during all three treatments. We conclude that elderly patients with mild thiazide-treated hypertension and mild renal insufficiency seem not to be at risk of developing additional renal compromise or of having their hypertension control diminished by treatment with these OTC analgesics for 7 days. PMID:8469621

  8. Endovascular management of renal transplant dysfunction secondary to hemodynamic effects related to ipsilateral femoral arteriovenous graft.

    PubMed

    Salsamendi, Jason; Pereira, Keith; Quintana, David; Bleicher, Drew; Tabbara, Marwan; Goldstein, Michael; Narayanan, Govindarajan

    2016-01-01

    Hemodialysis access options become complex in long-term treatment for patients with renal disease, while awaiting renal transplantation (RT). Once upper extremity sites are exhausted, lower extremities are used. RT is preferably in the contralateral iliac fossa, rarely ipsilateral. In current literature, RT dysfunction secondary to the hemodynamic effects of an ipsilateral femoral arteriovenous graft (AVG) has been rarely described. To our knowledge, AVG ligation is the only published technique for hemodynamic correction of an ipsilateral AVG. We present a simple, potentially reversible endovascular approach to manage the hemodynamic effects of an AVG, without potentially permanently losing future AVG access. PMID:26899147

  9. The Effects of Angiotensin II on Renal Water and Electrolyte Excretion in Normal and Caval Dogs*

    PubMed Central

    Porush, Jerome G.; Kaloyanides, George J.; Cacciaguida, Roy J.; Rosen, Stanley M.

    1967-01-01

    The effects of intravenous administration of angiotensin II on renal water and electrolyte excretion were examined during hydropenia, water diuresis, and hypotonic saline diuresis in anesthetized normal dogs and dogs with thoracic inferior vena cava constriction and ascites (caval dogs). The effects of unilateral renal artery infusion of a subpressor dose were also examined. During hydropenia angiotensin produced a decrease in tubular sodium reabsorption, with a considerably greater natriuresis in caval dogs, and associated with a decrease in free water reabsorption (TcH2O). Water and hypotonic saline diuresis resulted in an augmented angiotensin natriuresis, with a greater effect still observed in caval dogs. In these experiments free water excretion (CH2O) was limited to 8-10% of the glomerular filtration rate (GFR), although distal sodium load increased in every instance. In the renal artery infusion experiments a significant ipsilateral decrease in tubular sodium reabsorption was induced, particularly in caval dogs. These findings indicate that angiotensin has a direct effect on renal sodium reabsorption unrelated to a systemic circulatory alteration. The attenuation or prevention of the falls in GFR and effective renal plasma flow (ERPF) usually induced by angiotensin may partially account for the greater natriuretic response in caval dogs and the augmentation during water or hypotonic saline diuresis. However, a correlation between renal hemodynamics and the degree of natriuresis induced was not always present and, furthermore, GFR and ERPF decreased significantly during the intrarenal artery infusion experiments. Therefore, the present experiments indicate that another mechanism is operative in the control of the angiotensin natriuresis and suggest that alterations in intrarenal hemodynamics may play a role. The decrease in TcH2O and the apparent limitation of CH2O associated with an increase in distal sodium load localize the site of action of angiotensin

  10. Mechanism of Effect of Prostaglandin E1 on Renal Water Excretion

    PubMed Central

    Berl, T.; Schrier, R. W.

    1973-01-01

    The present study examined the effect of prostaglandin E1 (PGE1) on renal water excretion in the anesthetized dog. Renal perfusion pressure was kept constant by adjustment of a suprarenal aortic clamp. In seven experiments the intravenous administration of PGE1 (7 μg/min) significantly increased urinary osmolality from 76 to 381 mosmol (P < 0.001) and decreased free water clearance from 2.2 to - 0.02 ml/min (P < 0.001). These effects promptly were reversed with cessation of the infusion. This antidiuretic effect occurred both in innervated and denervated kidneys and was not associated with changes in glomerular filtration rate, renal vascular resistance, or solute excretion rate. In 10 experiments in hypophysectomized dogs no effect of intravenous PGE1 on free water clearance and urinary osmolality was observed. The intrarenal administration of PGE1 (1 μg/min) to six water-loaded and two hypophysectomized dogs caused no systemic vascular changes and increased rather than decreased free water clearance (2.83 to 4.08 ml/min, P < 0.001). No significant change in urinary osmolality occurred. Glomerular filtration rate was not altered by the intrarenal infusion, but reversible changes in solute excretion rate and renal vascular resistance occurred. These results thus indicate that the antidiuresis associated with intravenous PGE1 is mediated primarily by the release of vasopressin rather than alterations in renal hemodynamics or solute excretion. The diuretic effect of intrarenal PGE1 occurs in the absence of vasopressin and is most likely mediated primarily by increased distal delivery of tubular fluid to the diluting segment of the nephron rather than changes in water permeability of the renal tubular epithelium. PMID:4683884

  11. The effect of the American Heart Association step one diet on hyperlipidemia following renal transplantation.

    PubMed

    Moore, R A; Callahan, M F; Cody, M; Adams, P L; Litchford, M; Buckner, K; Galloway, J

    1990-01-01

    Cardiovascular disease is a frequent cause of morbidity and mortality following renal transplantation. The percentage of deaths due to ischemic cardiovascular disease and cerebrovascular accidents nearly equals that caused by infection among patients receiving their first transplant, according to data from the European Dialysis and Transplant Association Registry. Hypercholesterolemia is a risk factor for cardiovascular disease frequently identified following renal transplantation, and diets low in fat and cholesterol have been suggested as treatment. Previous studies have not reported the response of LDL cholesterol to dietary treatment, and it is this form of cholesterol that is most closely related to cardiovascular disease. The American Heart Association has provided nutritionists with guidelines for the treatment of hyperlipidemic patients which include the Step One Diet. Previous dietary studies of renal transplant recipients have allowed a slightly higher intake of fat than that currently recommended by the AHA. We wondered if an easily reproducible diet well known to nutritionists such as the AHA Step One Diet would be effective in lowering cholesterol levels in hyperlipidemic renal transplant recipients. The purpose of our study was not to define the mechanisms of posttransplant hyperlipidemia, but rather to assess the effectiveness of dietary intervention on hyperlipidemia following renal transplantation. PMID:2301029

  12. Chemical Profiles and Protective Effect of Hedyotis diffusa Willd in Lipopolysaccharide-Induced Renal Inflammation Mice

    PubMed Central

    Ye, Jian-Hong; Liu, Meng-Hua; Zhang, Xu-Lin; He, Jing-Yu

    2015-01-01

    Protective effect of Hedyotis diffusa (H. diffusa) Willd against lipopolysaccharide (LPS)-induced renal inflammation was evaluated by the productions of cytokines and chemokine, and the bioactive constituents of H. diffusa were detected by the ultra-fast liquid chromatography -diode array detector-quadrupole-time of flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) method. As the results showed, water extract of H. diffusa (equal to 5.0 g/kg body weight) obviously protected renal tissues, significantly suppressed the productions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1, as well as significantly promoted the production of IL-10 in serum and renal tissues. According the chemical profiles of H. diffusa, flavonoids, iridoid glycosides and anthraquinones were greatly detected in serum from H. diffusa extract treatment mice. Two main chemotypes, including eight flavonoids and four iridoid glycosides were found in renal tissues from H. diffusa extract treatment mice. The results demonstrated that water extract of H. diffusa had protective effect on renal inflammation, which possibly resulted from the bioactive constituents consisting of flavonoids, iridoids and anthraquinones. PMID:26580602

  13. Chemical Profiles and Protective Effect of Hedyotis diffusa Willd in Lipopolysaccharide-Induced Renal Inflammation Mice.

    PubMed

    Ye, Jian-Hong; Liu, Meng-Hua; Zhang, Xu-Lin; He, Jing-Yu

    2015-01-01

    Protective effect of Hedyotis diffusa (H. diffusa) Willd against lipopolysaccharide (LPS)-induced renal inflammation was evaluated by the productions of cytokines and chemokine, and the bioactive constituents of H. diffusa were detected by the ultra-fast liquid chromatography-diode array detector-quadrupole-time of flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) method. As the results showed, water extract of H. diffusa (equal to 5.0 g/kg body weight) obviously protected renal tissues, significantly suppressed the productions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1, as well as significantly promoted the production of IL-10 in serum and renal tissues. According the chemical profiles of H. diffusa, flavonoids, iridoid glycosides and anthraquinones were greatly detected in serum from H. diffusa extract treatment mice. Two main chemotypes, including eight flavonoids and four iridoid glycosides were found in renal tissues from H. diffusa extract treatment mice. The results demonstrated that water extract of H. diffusa had protective effect on renal inflammation, which possibly resulted from the bioactive constituents consisting of flavonoids, iridoids and anthraquinones. PMID:26580602

  14. The Effect of Pioglitazone on Antioxidant Levels and Renal Histopathology in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Kuru Karabas, Munire; Ayhan, Mediha; Guney, Engin; Serter, Mukadder; Meteoglu, Ibrahim

    2013-01-01

    Objective. Diabetic nephropathy is the most commonly seen cause of chronic renal failure, and oxidative stress is important in etiology. In the present study, favorable effects (if any) of the treatment with a thiazolidinedione group drug, pioglitazone, on antioxidant enzyme levels in the renal tissue, renal histopathology, and inflammatory cytokine levels have been investigated. Method. Forty male Wistar rats were divided into 4 groups as the control, diabetic control, and 10 and 30 mg pioglitazone-administered diabetic groups. After 4 weeks, antioxidant enzyme levels in renal tissues and inflammatory markers were investigated. Results. Blood glucose levels did not differ between the diabetic control and drug-administered groups. In pioglitazone-administered rats, histopathological findings such as tubular dilation, necrotic tubular epithelium, glomerular focal necrosis, and vascular consolidation were observed at a lesser extent than the diabetic control group. Any difference was not detected between the diabetic groups with respect to the levels of malondialdehyde, superoxide dismutase, catalase, glutathione, nitric oxide, interleukin-6, and tumor necrosis factor-alpha. Conclusion. Pioglitazone regressed development of histopathological lesions such as glomerular focal necrosis, tubular epithelial necrosis, tubular dilation, and vascular wall consolidation. However, any favorable effect on antioxidant enzyme levels in renal tissues and inflammation markers was not detected. PMID:23762597

  15. Effect of urinary stone disease and its treatment on renal function

    PubMed Central

    Mehmet, Necmettin Mercimek; Ender, Ozden

    2015-01-01

    Urolithiasis is a common disease that affects urinary tract in all age groups. Both in adults and in children, stone size, location, renal anatomy, and other factors, can influence the success of treatment modalities. Recently, there has been a great advancement in technology for minimally invasive management of urinary stones. The epoch of open treatment modalities has passed and currently there are much less invasive treatment approaches, such as percutaneous nephrolithotomy, ureteroscopy, shockwave lithotripsy, and retrograde internal Surgery. Furthermore, advancement in imaging technics ensures substantial knowledge that permit physician to decide the most convenient treatment method for the patient. Thus, effective and rapid treatment of urinary tract stones is substantial for the preservation of the renal function. In this review, the effects of the treatment options for urinary stones on renal function have been reviewed. PMID:25949941

  16. Prenatal programming-effects on blood pressure and renal function.

    PubMed

    Ritz, Eberhard; Amann, Kerstin; Koleganova, Nadezda; Benz, Kerstin

    2011-03-01

    Impaired intrauterine nephrogenesis-most clearly illustrated by low nephron number-is frequently associated with low birthweight and has been recognized as a powerful risk factor for renal disease; it increases the risks of low glomerular filtration rate, of more rapid progression of primary kidney disease, and of increased incidence of chronic kidney disease or end-stage renal disease. Another important consequence of impaired nephrogenesis is hypertension, which further amplifies the risk of onset and progression of kidney disease. Hypertension is associated with low nephron numbers in white individuals, but the association is not universal and is not seen in individuals of African origin. The derangement of intrauterine kidney development is an example of a more general principle that illustrates the paradigm of plasticity during development-that is, that transcription of the genetic code is modified by epigenetic factors (as has increasingly been documented). This Review outlines the concept of prenatal programming and, in particular, describes its role in kidney disease and hypertension. PMID:21283139

  17. Chronic Treatment with Atrial Natriuretic Peptide in Spontaneously Hypertensive Rats: Beneficial Renal Effects and Sex Differences

    PubMed Central

    Romero, Mariana; Caniffi, Carolina; Bouchet, Gonzalo; Costa, María A.; Elesgaray, Rosana; Arranz, Cristina; Tomat, Analía L.

    2015-01-01

    Objective The aim of this study was to investigate the effects of chronic treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide (NO) system, oxidative stress, collagen content and apoptosis in kidneys of spontaneously hypertensive rats (SHR), as well as sex-related differences in the response to the treatment. Methods 10 week-old male and female SHR were infused with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis were determined. After treatment, renal NO synthase (NOS) activity and eNOS expression were evaluated. Thiobarbituric acid-reactive substances (TBARS), glutathione concentration and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in the kidney. Collagen was identified in renal slices by Sirius red staining and apoptosis by Tunel assay. Results Female SHR showed lower SBP, oxidative stress, collagen content and apoptosis in kidney, and higher renal NOS activity and eNOS protein content, than males. ANP lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS expression in both sexes. Renal response to ANP was more marked in females than in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and increased glutathione concentration and activity of GPx and SOD enzymes in both sexes. Conclusions Female SHR exhibited less organ damage than males. Chronic ANP treatment would ameliorate hypertension and end-organ damage in the kidney by reducing oxidative stress, increasing NO-system activity, and diminishing collagen content and apoptosis, in both sexes. PMID:25774801

  18. Pulmonary function in chronic renal failure: effects of dialysis and transplantation.

    PubMed Central

    Bush, A; Gabriel, R

    1991-01-01

    Many possible pulmonary complications of renal disease have been described, but little is known of their physiological importance or the effects on them of different forms of renal replacement therapy. Four groups were recruited, each containing 20 patients. The groups consisted of patients with chronic renal failure before dialysis (group 1); patients receiving continuous ambulatory peritoneal dialysis, never having received a transplant (group 2); patients receiving haemodialysis, never having received a transplant (group 3); and patients after their first successful cadaveric renal transplant (group 4). All were attending the same regional dialysis and transplant unit. None was known to have clinically important lung or chest wall disease. Flow-volume loops were recorded before and after 400 micrograms of salbutamol, and plethysmographic lung volumes and airway conductance and single breath carbon monoxide transfer factor were measured. Only nine of 80 patients had normal lung function. The reductions in spirometric values were minor. Whole lung carbon monoxide transfer factor was reduced in all groups (mean % predicted with 95% confidence intervals: group 1 81.7% (74-89%); group 2 69.7% (62-77%); group 3 87.5% (80-96%); group 4 82.5% (78-87%]. The values were significantly lower in those having continuous ambulatory peritoneal dialysis (group 2). Residual volume was reduced significantly in the group who had undergone renal transplantation (85.7%, 77-94%). There was no correlation between these changes and smoking habit, age, duration or severity of renal failure, duration of treatment, or biochemical derangement. It is concluded that abnormal lung function is common in renal disease. The main change is a reduction in carbon monoxide transfer that persists after transplantation. The likeliest explanation is that subclinical pulmonary oedema progresses to fibrosis before transplantation. The fibrosis may worsen further to cause the reduced residual volume in the

  19. Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury.

    PubMed

    Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Hibi, Chihiro; Nakamura, Takashi; Murase, Takayo; Oikawa, Tsuyoshi; Hoshino, Seiko; Hisamichi, Mikako; Hirata, Kazuaki; Kimura, Kenjiro; Shibagaki, Yugo

    2016-06-01

    The aim of the present study was to reveal the effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model. PMID:27029427

  20. Crack patterning effects in evolution of damage

    SciTech Connect

    Lacy, T.E.; McDowell, D.L.; Taireja, R.

    1995-12-31

    Recent micromechanically inspired phenomenological theories using internal state variable representations of damage have been used to predict the thermomechanical behavior of microcracking solids. These models do not, in an explicit manner, account for distributions of microcracks in a Representative Volume Element (RVE) and have been successfully used only to determine the effective moduli of damaged solids. It has been demonstrated that while the distribution. and interaction of damage entities within a RVE have a minor effect on the effective moduli, they have a significant effect on the evolution of damage and failure at the macroscale. Damage evolution rates cannot, in general, be adequately described by such theories because of their inability to account for interactions between damage entities in an arbitrary distribution. In the present work, finite element solutions to two-dimensional problems with growing microcracks are obtained for both uniform and non-uniform crack arrays. Effective moduli and RVE-averaged driving forces for non-uniformly distributed interacting crack systems are calculated across a range of microcrack distribution parameters. Results are compared to existing solutions. Damage evolution is studied by allowing incremental advance under specified growth criteria of different crack systems within a RVE. Concepts for the inclusion of discrete sub-RVE length scales in the specific Helmholtz free energy and dissipation potentials are outlined. Use of multivariate distribution functions to characterize damage is discussed.

  1. Hemorrhagic Renal Angiomyolipoma in Pregnancy Effectively Managed by Immediate Cesarean Section and Elective Transcatheter Arterial Embolization: A Case Report

    PubMed Central

    Sawada, Norifumi; Miyamoto, Tatsuya; Mitsui, Takahiko; Zakoji, Hidenori; Takeda, Masayuki

    2016-01-01

    Abstract Renal angiomyolipoma (AML) is a benign renal tumor with a risk of rupture in intratumoral aneurysms. Although renal AML in pregnancy is rare, risk of rupture is greater. Management for AML and childbirth is important during pregnancy; however, it is undefined yet. We present a case of hemorrhagic angiomyolipoma in pregnancy that is effectively managed by immediate cesarean section and elective transcatheter arterial embolization.

  2. Hemorrhagic Renal Angiomyolipoma in Pregnancy Effectively Managed by Immediate Cesarean Section and Elective Transcatheter Arterial Embolization: A Case Report.

    PubMed

    Kira, Satoru; Sawada, Norifumi; Miyamoto, Tatsuya; Mitsui, Takahiko; Zakoji, Hidenori; Takeda, Masayuki

    2016-01-01

    Renal angiomyolipoma (AML) is a benign renal tumor with a risk of rupture in intratumoral aneurysms. Although renal AML in pregnancy is rare, risk of rupture is greater. Management for AML and childbirth is important during pregnancy; however, it is undefined yet. We present a case of hemorrhagic angiomyolipoma in pregnancy that is effectively managed by immediate cesarean section and elective transcatheter arterial embolization. PMID:27579420

  3. The Evolution of Multivariate Maternal Effects

    PubMed Central

    Kuijper, Bram; Johnstone, Rufus A.; Townley, Stuart

    2014-01-01

    There is a growing interest in predicting the social and ecological contexts that favor the evolution of maternal effects. Most predictions focus, however, on maternal effects that affect only a single character, whereas the evolution of maternal effects is poorly understood in the presence of suites of interacting traits. To overcome this, we simulate the evolution of multivariate maternal effects (captured by the matrix M) in a fluctuating environment. We find that the rate of environmental fluctuations has a substantial effect on the properties of M: in slowly changing environments, offspring are selected to have a multivariate phenotype roughly similar to the maternal phenotype, so that M is characterized by positive dominant eigenvalues; by contrast, rapidly changing environments favor Ms with dominant eigenvalues that are negative, as offspring favor a phenotype which substantially differs from the maternal phenotype. Moreover, when fluctuating selection on one maternal character is temporally delayed relative to selection on other traits, we find a striking pattern of cross-trait maternal effects in which maternal characters influence not only the same character in offspring, but also other offspring characters. Additionally, when selection on one character contains more stochastic noise relative to selection on other traits, large cross-trait maternal effects evolve from those maternal traits that experience the smallest amounts of noise. The presence of these cross-trait maternal effects shows that individual maternal effects cannot be studied in isolation, and that their study in a multivariate context may provide important insights about the nature of past selection. Our results call for more studies that measure multivariate maternal effects in wild populations. PMID:24722346

  4. The Beneficial Effects of Renal Transplantation on Altered Oxidative Status of ESRD Patients.

    PubMed

    Cerrillos-Gutiérrez, José Ignacio; Miranda-Díaz, Alejandra Guillermina; Preciado-Rojas, Priscila; Gómez-Navarro, Benjamín; Sifuentes-Franco, Sonia; Carrillo-Ibarra, Sandra; Andrade-Sierra, Jorge; Rojas-Campos, Enrique; Cueto-Manzano, Alfonso Martín

    2016-01-01

    Renal transplantation (RT), has been considered the best therapeutic option for end stage renal disease (ESRD). Objective. To determine the effect of RT on the evolution of oxidative DNA status. Methods. Prospective cohort (N = 50 receptors of RT); genotoxic damage, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and DNA repair enzyme, human 8-oxoguanine-DNA-N- glycosylase-1 (hOGG1); and antioxidants, superoxide dismutase (SOD) and glutathione peroxidase (GPx), were evaluated. Results. Before RT, 8-OHdG were significantly elevated (11.04 ± 0.90 versus 4.73 ± 0.34 ng/mL) compared to healthy controls (p = 0.001), with normalization after 6 months of 4.78 ± 0.34 ng/mL (p < 0.001). The same phenomenon was observed with hOGG1 enzyme before RT with 2.14 ± 0.36 ng/mL (p = 0.01) and decreased significantly at the end of the study to 1.20 ng/mL (p < 0.001) but was higher than controls, 0.51 ± 0.07 ng/mL (p < 0.03). Antioxidant SOD was elevated at 24.09 ± 1.6 IU/mL versus healthy controls (p = 0.001) before RT; however, 6 months after RT it decreased significantly to 16.9 ± 1.6 IU/mL (p = 0.002), without achieving the levels of healthy controls (p = 0.01). The GPx, before RT, was significantly diminished with 24.09 ± 1.6 IU/mL versus healthy controls (39.0 ± 1.58) (p = 0.01), while, in the final results, levels increased significantly to 30.38 ± 3.16 IU/mL (p = 0.001). Discussion. Patients with ESRD have important oxidative damage before RT. The RT significantly reduces oxidative damage and partially regulates the antioxidant enzymes (SOD and GPx). PMID:27547292

  5. The Beneficial Effects of Renal Transplantation on Altered Oxidative Status of ESRD Patients

    PubMed Central

    Cerrillos-Gutiérrez, José Ignacio; Preciado-Rojas, Priscila; Gómez-Navarro, Benjamín; Sifuentes-Franco, Sonia; Carrillo-Ibarra, Sandra; Andrade-Sierra, Jorge; Rojas-Campos, Enrique; Cueto-Manzano, Alfonso Martín

    2016-01-01

    Renal transplantation (RT), has been considered the best therapeutic option for end stage renal disease (ESRD). Objective. To determine the effect of RT on the evolution of oxidative DNA status. Methods. Prospective cohort (N = 50 receptors of RT); genotoxic damage, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and DNA repair enzyme, human 8-oxoguanine-DNA-N- glycosylase-1 (hOGG1); and antioxidants, superoxide dismutase (SOD) and glutathione peroxidase (GPx), were evaluated. Results. Before RT, 8-OHdG were significantly elevated (11.04 ± 0.90 versus 4.73 ± 0.34 ng/mL) compared to healthy controls (p = 0.001), with normalization after 6 months of 4.78 ± 0.34 ng/mL (p < 0.001). The same phenomenon was observed with hOGG1 enzyme before RT with 2.14 ± 0.36 ng/mL (p = 0.01) and decreased significantly at the end of the study to 1.20 ng/mL (p < 0.001) but was higher than controls, 0.51 ± 0.07 ng/mL (p < 0.03). Antioxidant SOD was elevated at 24.09 ± 1.6 IU/mL versus healthy controls (p = 0.001) before RT; however, 6 months after RT it decreased significantly to 16.9 ± 1.6 IU/mL (p = 0.002), without achieving the levels of healthy controls (p = 0.01). The GPx, before RT, was significantly diminished with 24.09 ± 1.6 IU/mL versus healthy controls (39.0 ± 1.58) (p = 0.01), while, in the final results, levels increased significantly to 30.38 ± 3.16 IU/mL (p = 0.001). Discussion. Patients with ESRD have important oxidative damage before RT. The RT significantly reduces oxidative damage and partially regulates the antioxidant enzymes (SOD and GPx). PMID:27547292

  6. Protective effects of genetic inhibition of Discoidin Domain Receptor 1 in experimental renal disease

    PubMed Central

    Kerroch, Monique; Alfieri, Carlo; Dorison, Aude; Boffa, Jean-Jacques; Chatziantoniou, Christos; Dussaule, Jean-Claude

    2016-01-01

    Chronic kidney disease is a progressive incurable pathology affecting millions of people. Intensive investigations aim to identify targets for therapy. We have previously demonstrated that abnormal expression of the Discoidin Domain Receptor 1 (DDR1) is a key factor of renal disease by promoting inflammation and fibrosis. The present study investigates whether blocking the expression of DDR1 after the initiation of renal disease can delay or arrest the progression of this pathology. Severe renal disease was induced by either injecting nephrotoxic serum (NTS) or performing unilateral ureteral obstruction in mice, and the expression of DDR1 was inhibited by administering antisense oligodeoxynucleotides either at 4 or 8 days after NTS (corresponding to early or more established phases of disease, respectively), or at day 2 after ligation. DDR1 antisense administration at day 4 stopped the increase of proteinuria and protected animals against the progression of glomeruloneprhitis, as evidenced by functional, structural and cellular indexes. Antisense administration at day 8 delayed progression –but to a smaller degree- of renal disease. Similar beneficial effects on renal structure and inflammation were observed with the antisense administration of DDR1 after ureteral ligation. Thus, targeting DDR1 can be a promising strategy in the treatment of chronic kidney disease. PMID:26880216

  7. Protective effects of genetic inhibition of Discoidin Domain Receptor 1 in experimental renal disease.

    PubMed

    Kerroch, Monique; Alfieri, Carlo; Dorison, Aude; Boffa, Jean-Jacques; Chatziantoniou, Christos; Dussaule, Jean-Claude

    2016-01-01

    Chronic kidney disease is a progressive incurable pathology affecting millions of people. Intensive investigations aim to identify targets for therapy. We have previously demonstrated that abnormal expression of the Discoidin Domain Receptor 1 (DDR1) is a key factor of renal disease by promoting inflammation and fibrosis. The present study investigates whether blocking the expression of DDR1 after the initiation of renal disease can delay or arrest the progression of this pathology. Severe renal disease was induced by either injecting nephrotoxic serum (NTS) or performing unilateral ureteral obstruction in mice, and the expression of DDR1 was inhibited by administering antisense oligodeoxynucleotides either at 4 or 8 days after NTS (corresponding to early or more established phases of disease, respectively), or at day 2 after ligation. DDR1 antisense administration at day 4 stopped the increase of proteinuria and protected animals against the progression of glomeruloneprhitis, as evidenced by functional, structural and cellular indexes. Antisense administration at day 8 delayed progression -but to a smaller degree- of renal disease. Similar beneficial effects on renal structure and inflammation were observed with the antisense administration of DDR1 after ureteral ligation. Thus, targeting DDR1 can be a promising strategy in the treatment of chronic kidney disease. PMID:26880216

  8. Effects of long-term training on the progression of chronic renal failure in rats.

    PubMed

    Bergamaschi, C T; Boim, M A; Moura, L A; Piçarro, I C; Schor, N

    1997-02-01

    To evaluate the effects of long-term exercise on the progression of chronic renal failure (CRF), adult Munich-Wistar rats with 5/6 renal mass ablation were submitted to treadmill exercise for 30 min 5 times/wk for 60 d. Whole kidney function and glomerular hemodynamics, proteinuria, and glomerular sclerosis were evaluated in 4 groups: Control, Sham trained (Sham + Ex), rats submitted to 5/6 nephrectomy (CRF) and maintained sedentary, and rats with 5/6 nephrectomy and trained (CRF + Ex). The groups with chronic renal failure (sedentary and trained) presented a reduction in total glomerular filtration rate (GFR) and in renal plasma flow (RPF), accompanied by an increase in single nephron GFR (SNGFR) and glomerular plasma flow (QA). However, the CRF + EX group did not show the glomerular hypertension observed in the CRF group. Despite the normalization of glomerular hypertension, proteinuria and sclerosis index were not different from the CRF sedentary group. Physical training provoked a vasodilatation of efferent arterioles, which induced the normalization of glomerular hypertension. These results suggest that the reduction alone of glomerular hypertension induced by exercise does not prevent the progression of renal disease, indicating the participation of other associated factors in this experimental model. PMID:9044218

  9. Renal Protective Effect of Probucol in Rats with Contrast-Induced Nephropathy and its Underlying Mechanism

    PubMed Central

    Wang, Na; Wei, Ri-bao; Li, Qing-ping; Yang, Xi; Li, Ping; Huang, Meng-jie; Wang, Rui; Cai, Guang-yan; Chen, Xiang-mei

    2015-01-01

    Background Contrast-induced nephropathy (CIN) refers to acute renal damage that occurs after the use of contrast agents. This study investigated the renal protective effect of probucol in a rat model of contrast-induced nephropathy and the mechanism of its effect. Material/Methods Twenty-eight Wistar rats were randomly divided into the control group, model group, N-acetylcysteine(NAC) group, and probucol group. We used a rat model of iopromide-induced CIN. One day prior to modeling, the rats received gavage. At 24 h after the modeling, blood biochemistry and urine protein were assessed. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in renal tissue. Kidney sections were created for histopathological examination. Results The model group of rats showed significantly elevated levels of blood creatinine, urea nitrogen, 24-h urine protein, histopathological scores, and parameters of oxidative stress (P<0.05). Both the NAC and probucol groups demonstrated significantly lower Scr, BUN, and urine protein levels compared to the model group (P<0.05), with no significant difference between these 2 groups. The NAC group and the probucol group had significantly lower MDA and higher SOD than the model group at 24 h after modeling (P<0.05). The 8-OHdG-positive tubule of the probucol group and NAC group were significantly lower than those of the model group (p=0.046, P=0.0008), with significant difference between these 2 groups (P=0.024). Conclusions Probucol can effectively reduce kidney damage caused by contrast agent. The underlying mechanism may be that probucol accelerates the recovery of renal function and renal pathology by reducing local renal oxidative stress. PMID:26408630

  10. Pharmacokinetics, pharmacology of atenolol and effect of renal disease.

    PubMed Central

    Wan, S H; Koda, R T; Maronde, R F

    1979-01-01

    1. The pharmacokinetics of intravenous and oral atenolol (50 mg) in six healthy volunteers was studied. Plasma, saliva and urine were collected up to 24 h after each dose. 2. There was no significant difference in atenolol half-life when administered by the two routes. Bioavailability of the orally administered atenolol was 50%. 3. Atenolol levels in saliva required about 2 h to reach equilibrium with plasma drug levels. 4. A comparison between the pharmacokinetics and pharmacology of atenolol was made in twelve healthy subjects. 5. Dose-independent pharmacokinetics were observed. Reductions in resting heart rate and arterial blood pressure were proportional to either the logarithm of dose or area under the plasma concentration time curve or cumulative urinary atenolol excretion. 6. Plasma elimination half-life in five subjects with renal failure was prolonged. PMID:465278

  11. SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair

    PubMed Central

    Kanu, N; Grönroos, E; Martinez, P; Burrell, R A; Yi Goh, X; Bartkova, J; Maya-Mendoza, A; Mistrík, M; Rowan, A J; Patel, H; Rabinowitz, A; East, P; Wilson, G; Santos, C R; McGranahan, N; Gulati, S; Gerlinger, M; Birkbak, N J; Joshi, T; Alexandrov, L B; Stratton, M R; Powles, T; Matthews, N; Bates, P A; Stewart, A; Szallasi, Z; Larkin, J; Bartek, J; Swanton, C

    2015-01-01

    Defining mechanisms that generate intratumour heterogeneity and branched evolution may inspire novel therapeutic approaches to limit tumour diversity and adaptation. SETD2 (Su(var), Enhancer of zeste, Trithorax-domain containing 2) trimethylates histone-3 lysine-36 (H3K36me3) at sites of active transcription and is mutated in diverse tumour types, including clear cell renal carcinomas (ccRCCs). Distinct SETD2 mutations have been identified in spatially separated regions in ccRCC, indicative of intratumour heterogeneity. In this study, we have addressed the consequences of SETD2 loss-of-function through an integrated bioinformatics and functional genomics approach. We find that bi-allelic SETD2 aberrations are not associated with microsatellite instability in ccRCC. SETD2 depletion in ccRCC cells revealed aberrant and reduced nucleosome compaction and chromatin association of the key replication proteins minichromosome maintenance complex component (MCM7) and DNA polymerase δ hindering replication fork progression, and failure to load lens epithelium-derived growth factor and the Rad51 homologous recombination repair factor at DNA breaks. Consistent with these data, we observe chromosomal breakpoint locations are biased away from H3K36me3 sites in SETD2 wild-type ccRCCs relative to tumours with bi-allelic SETD2 aberrations and that H3K36me3-negative ccRCCs display elevated DNA damage in vivo. These data suggest a role for SETD2 in maintaining genome integrity through nucleosome stabilization, suppression of replication stress and the coordination of DNA repair. PMID:25728682

  12. SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair.

    PubMed

    Kanu, N; Grönroos, E; Martinez, P; Burrell, R A; Yi Goh, X; Bartkova, J; Maya-Mendoza, A; Mistrík, M; Rowan, A J; Patel, H; Rabinowitz, A; East, P; Wilson, G; Santos, C R; McGranahan, N; Gulati, S; Gerlinger, M; Birkbak, N J; Joshi, T; Alexandrov, L B; Stratton, M R; Powles, T; Matthews, N; Bates, P A; Stewart, A; Szallasi, Z; Larkin, J; Bartek, J; Swanton, C

    2015-11-12

    Defining mechanisms that generate intratumour heterogeneity and branched evolution may inspire novel therapeutic approaches to limit tumour diversity and adaptation. SETD2 (Su(var), Enhancer of zeste, Trithorax-domain containing 2) trimethylates histone-3 lysine-36 (H3K36me3) at sites of active transcription and is mutated in diverse tumour types, including clear cell renal carcinomas (ccRCCs). Distinct SETD2 mutations have been identified in spatially separated regions in ccRCC, indicative of intratumour heterogeneity. In this study, we have addressed the consequences of SETD2 loss-of-function through an integrated bioinformatics and functional genomics approach. We find that bi-allelic SETD2 aberrations are not associated with microsatellite instability in ccRCC. SETD2 depletion in ccRCC cells revealed aberrant and reduced nucleosome compaction and chromatin association of the key replication proteins minichromosome maintenance complex component (MCM7) and DNA polymerase δ hindering replication fork progression, and failure to load lens epithelium-derived growth factor and the Rad51 homologous recombination repair factor at DNA breaks. Consistent with these data, we observe chromosomal breakpoint locations are biased away from H3K36me3 sites in SETD2 wild-type ccRCCs relative to tumours with bi-allelic SETD2 aberrations and that H3K36me3-negative ccRCCs display elevated DNA damage in vivo. These data suggest a role for SETD2 in maintaining genome integrity through nucleosome stabilization, suppression of replication stress and the coordination of DNA repair. PMID:25728682

  13. Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ)-Induced Diabetic Mice

    PubMed Central

    Zhang, Xiuli; He, Hui; Liang, Dan; Jiang, Yan; Liang, Wei; Chi, Zhi-Hong; Ma, Jianfei

    2016-01-01

    Diabetic nephropathy (DN) is a serious diabetic complication with renal hypertrophy and expansion of extracellular matrices in renal fibrosis. Epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells may be involved in the main mechanism. Berberine (BBR) has been shown to have antifibrotic effects in liver, kidney and lung. However, the mechanism of cytoprotective effects of BBR in DN is still unclear. In this study, we investigated the curative effects of BBR on tubulointerstitial fibrosis in streptozotocin (STZ)-induced diabetic mice and the high glucose (HG)-induced EMT in NRK 52E cells. We found that BBR treatment attenuated renal fibrosis by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Further revealed that BBR abrogated HG-induced EMT and oxidative stress in relation not only with the activation of Nrf2 and two Nrf2-targeted antioxidative genes (NQO-1 and HO-1), but also with the suppressing the activation of TGF-β/Smad signaling pathway. Importantly, knockdown Nrf2 with siRNA not only abolished the BBR-induced expression of HO-1 and NQO-1 but also removed the inhibitory effect of BBR on HG-induced activation of TGF-β/Smad signaling as well as the anti-fibrosis effects. The data from present study suggest that BBR can ameliorate tubulointerstitial fibrosis in DN by activating Nrf2 pathway and inhibiting TGF-β/Smad/EMT signaling activity. PMID:27529235

  14. Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ)-Induced Diabetic Mice.

    PubMed

    Zhang, Xiuli; He, Hui; Liang, Dan; Jiang, Yan; Liang, Wei; Chi, Zhi-Hong; Ma, Jianfei

    2016-01-01

    Diabetic nephropathy (DN) is a serious diabetic complication with renal hypertrophy and expansion of extracellular matrices in renal fibrosis. Epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells may be involved in the main mechanism. Berberine (BBR) has been shown to have antifibrotic effects in liver, kidney and lung. However, the mechanism of cytoprotective effects of BBR in DN is still unclear. In this study, we investigated the curative effects of BBR on tubulointerstitial fibrosis in streptozotocin (STZ)-induced diabetic mice and the high glucose (HG)-induced EMT in NRK 52E cells. We found that BBR treatment attenuated renal fibrosis by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Further revealed that BBR abrogated HG-induced EMT and oxidative stress in relation not only with the activation of Nrf2 and two Nrf2-targeted antioxidative genes (NQO-1 and HO-1), but also with the suppressing the activation of TGF-β/Smad signaling pathway. Importantly, knockdown Nrf2 with siRNA not only abolished the BBR-induced expression of HO-1 and NQO-1 but also removed the inhibitory effect of BBR on HG-induced activation of TGF-β/Smad signaling as well as the anti-fibrosis effects. The data from present study suggest that BBR can ameliorate tubulointerstitial fibrosis in DN by activating Nrf2 pathway and inhibiting TGF-β/Smad/EMT signaling activity. PMID:27529235

  15. Effects of positive acceleration /+Gz/ on renal function and plasma renin in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Shubrooks, S. J., Jr.; Fishman, L. M.; Duncan, D. C.

    1974-01-01

    The effects of positive radial centrifugation (+Gz) on plasma resin activity (PRA) and renal function were assessed in 15 normal male subjects under carefully controlled conditions of Na, K, and water intake. Twenty minutes of +2.0 Gz resulted in significant decreases in the mean rate of sodium excretion and creatine clearance and in a doubling of PRA in seven sodium-depleted subjects (10 meq Na intake). In eight sodium-replete subjects (200 mq Na intake), 30 min of +2.0 Gz was also associated with a decrease in the mean rate of sodium excretion. As a consequence of a concurrent decrease in creatine clearance, the fractional excretion of sodium during centrifugation did not differ from control, suggesting that the changes in Na excretion were mediated primarily by renal hemodynamic factors, although enhanced renal tubular sodium reabsorption may also have played a role.

  16. Effects of PAF antagonists on renal vascular escape and tachyphylaxis in perfused rabbit kidney.

    PubMed

    Ferreira, M G; Braquet, P; Fonteles, M C

    1991-12-01

    Renal vascular escape is a physiological phenomenon of adaptation that occurs in vascular smooth muscle. It has been described in many preparations subjected to electrical stimulation or treated with vasoactive agents, such as noreprinephrine, angiotensin and vasopressin. We have recently demonstrated that a naturally occurring ginkgolide (BN 52021), which is a PAF antagonist, was able to block norepinephrine-induced escape in perfused rabbit kidney. In the present work other PAF antagonists, such as the ginkgolides BN 52022 and BN 52024, and the synthetic compounds 48740 RP and WEB 2086, were tested. Their effects on renal vascular escape, perfusion pressure and tachyphylaxis were evaluated. They all were shown to block the escape. Among the ginkgolides, BN 52024 is generally recognized as one of the weaker PAF antagonists. However, in spite of this, BN 52024 was able to significantly and simultaneously block renal vascular escape and tachyphylaxis in perfused rabbit kidney infused with norepinephrine. PMID:1819726

  17. Effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol.

    PubMed Central

    Yamamoto, T; Moriwaki, Y; Takahashi, S; Suda, M; Higashino, K

    1991-01-01

    The effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol were investigated. Pyrazinamide decreased the mean (SEM) fractional clearance of oxypurinol from 19.2 (2.1) to 8.8 (1.5). Probenecid increased the fractional clearance of oxypurinol from 14.1 (3.5) to 24.8 (4.1). Benzbromarone increased the fractional clearance of oxypurinol from 15.6 (2.3) to 33.8 (2.8). These results suggest that oxypurinol may be secreted by 'an organic acid system' and that oxypurinol is reabsorbed at a putative postsecretory site of the renal tubules. PMID:1929586

  18. Renal colic in adults: NSAIDs and morphine are effective for pain relief.

    PubMed

    2009-10-01

    (1) Renal colic is an acute syndrome involving unilateral flank pain, linked to an obstruction in the upper urinary tract. The pain is often intense. After having considered other diagnoses and checked for signs of complication (fever, oligoanuria), the first step is to control the pain; (2) Which non-invasive treatments have a positive risk-benefit balance in relieving this type of pain? To answer this question, we reviewed the available evidence, based on the standard Prescrire methodology; (3) According to a meta-analysis of 20 trials, nonsteroidal antiinflammatory drugs (NSAIDs) and strong opioid analgesics have comparable efficacy. The most widely studied NSAID is diclofenac, given intramuscularly at a dose of 50 mg or 75 mg. Pethidine is the best-assessed strong opioid, given intramuscularly at a dose of 50 mg to 100 mg, which corresponds to about 5 mg to 10 mg of morphine. Morphine is given intravenously; subcutaneous administration is an alternative although it has not been evaluated in renal colic; (4) In clinical trials, NSAIDs were associated with fewer adverse effects than opioids, which cause vomiting in about 20% of patients (versus about 6% with an NSAID); (5) NSAIDs expose patients to a risk of functional renal impairment, especially in patients with heart failure, renal artery stenosis, dehydration, renal impairment or ongoing treatment with a nephrotoxic drug, and the very elderly. NSAIDs should never be used during pregnancy; (6) According to one trial in 130 patients, the analgesic effect of the morphine and NSAID combination was greater than either agent used alone, in about 10% of patients; (7) Paracetamol has not been evaluated in comparative trials of renal colic, even for moderate pain; (8) Scopolamine is the only antispasmodic to have been evaluated in a comparative trial. Adding scopolamine to morphine did not seem to provide additional efficacy; (9) Other drugs, which have not been adequately tested as of early 2009, have no documented

  19. Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells

    PubMed Central

    Rombo, Roman; Weiher, Hans; Schmidt-Wolf, Ingo G.H.

    2016-01-01

    We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK) assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer. PMID:27141211

  20. Systemic and renal effects of an ETA receptor subtype-specific antagonist in healthy subjects

    PubMed Central

    Schmetterer, Leopold; Dallinger, Susanne; Bobr, Barbara; Selenko, Nicole; Eichler, Hans-Georg; Wolzt, Michael

    1998-01-01

    Endothelins (ETs) might play a pathophysiological role in a variety of vascular diseases. The aim of the present study was to characterize the effects of BQ-123, a specific ETA receptor antagonist on systemic and renal haemodynamics in healthy subjects. This was done at baseline and during infusion of exogenous ET-1.The study was performed in a balanced, randomized, placebo-controlled, double blind 4 way cross-over design in 10 healthy male subjects. Subjects received co-infusions of ET-1 (2.5 ng kg−1 min−1 for 120 min) or placebo and BQ-123 (15 μg min−1 for 60 min and subsequently 60 μg min−1 for 60 min) or placebo. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by the para-aminohippurate (PAH) and the inulin plasma clearance method, respectively.BQ-123 alone had no renal or systemic haemodynamic effect. ET-1 significantly reduced RPF (−24%, P<0.001) and GFR (−12%, P=0.034). These effects were abolished by co-infusion of either dose of BQ-123 (RPF: P=0.0012; GFR: P=0.020).BQ-123 reversed the renal haemodynamic effects induced by exogenous ET-1 in vivo. This indicates that vasoconstriction in the kidney provoked by ET-1 is predominantly mediated by the ETA receptor subtype. PMID:9692778

  1. Analgesic effect and tolerance of Voltaren and Ketogan in acute renal or ureteric colic.

    PubMed

    Sommer, P; Kromann-Andersen, B; Lendorf, A; Lyngdorf, P; Møller, P

    1989-01-01

    Fifty-six patients with renal or ureteric colic were entered into a randomised, prospective, double-blind investigation of the analgesic efficacy and tolerance of Voltaren versus Ketogan, both administered intramuscularly. There were no significant differences regarding pain-relief but side effects were fewer in patients treated with Voltaren. PMID:2645969

  2. Renal angiotensin-converting enzyme localization in diabetic rats and the effect of low protein diet.

    PubMed

    Mizuiri, S; Kobayashi, M; Nakanishi, T; Yoshikawa, H; Miyagi, M; Tanegashima, M; Sakai, K; Hayashi, I; Fushimi, T; Hasegawa, A

    1997-01-01

    Recent evidence suggests a role of angiotensin-converting enzyme (ACE) in diabetic nephropathy. The effect of diabetes and low protein diet on renal immunohistochemical ACE localization was studied in streptozotocin-induced DM rats. Immunohistochemical ACE localization was reduced in DM rats, and a low protein diet partially resolved this abnormality while inhibiting the progression of diabetic nephropathy. PMID:9200410

  3. Effect of gender differences on the regulation of renal ischemia-reperfusion-induced inflammation in mice.

    PubMed

    Kang, Kyung Pyo; Lee, Jung Eun; Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Lee, Sik; Hwang, Hong Pil; Kim, Won; Park, Sung Kwang

    2014-06-01

    Inflammation is a key mediator of renal ischemia-reperfusion (IR) injury. Gender disparities have been reported in acute and chronic kidney disease. In particular, males are considered to be more susceptible to renal ischemic injury compared with females according to animal studies. The purpose of the present study was to investigate the effect of gender on the renal inflammatory response following acute renal IR injury in mice. Experiments were performed in male and female C57BL/6 mice. Two weeks prior to the study, castration or ovariectomy were performed and testosterone propionate (100 µg/kg) or 17β-estradiol (100 µg/kg) was injected. Acute kidney injury (AKI) was induced by bilateral clamping of the renal pedicle for 23 min. Histological examination, western blot analysis and quantitative polymerase chain reaction were performed. In the acute renal IR injury model, the female mice were more resistant to kidney injury compared with the male mice. However, castration of the male mice reduced the levels of IR-induced tubular injury and macrophage infiltration compared with those in the injured male mice. Supplementation of testosterone reversed this protective effect in the male AKI model. Depletion of estrogen in the female mice increased the levels of IR-induced tubular injury and macrophage infiltration compared with those in the injured female mice. However, supplementation of estrogen in the ovariectomized female mice attenuated the IR-induced tubular injury and reduced the levels of macrophage infiltration. The expression levels of inflammatory cytokines, including tumor necrosis factor-α, monocyte chemotactic protein-1, interferon-γ and chemokine (C-C motif) ligand 17, were elevated in the male AKI mice compared with those in the control male mice, and were attenuated by castration. Estrogen depletion in the female mice significantly increased the expression levels of the renal inflammatory cytokines compared with those in the injured female mice, and

  4. Effect of renal denervation on the antinatriuretic response to morphine administration in conscious rats.

    PubMed

    Walker, L A; Murphy, J C

    1986-06-01

    The effect of surgical denervation on the antinatriuretic response to morphine was assessed in conscious rats prepared with arterial and venous catheters and bladder cannulas. In sham-operated animals, morphine sulfate (4 mg/kg i.v. plus 2 mg/kg X hr) caused a marked reduction in sodium excretion (650 +/- 218 vs. 2394 +/- 265 nEq/100 g X min in vehicle-treated animals; P less than .05). Although glomerular filtration rate was reduced, fractional excretion of sodium, expressed as a percentage of the filtered load, was also markedly decreased by morphine (0.62 +/- 0.18 vs. 1.51 +/- 0.15% in the vehicle group; P less than .05). The changes in sodium excretion were readily reversed by naloxone. In rats subjected to the renal denervation procedure, morphine had no effect on sodium excretion (1614 +/- 261 vs. 1926 +/- 520 nEq/100 g X min) or on fractional sodium excretion (1.92 +/- 0.50 vs. 1.41 +/- 0.37%). However, glomerular filtration rate was reduced by morphine as in the sham-denervated rats. Blood pressure and heart rate were not significantly affected by morphine in either group. The results suggest that morphine enhances renal tubular sodium reabsorption, at least in part, by a mechanism dependent on intact renal nerves. Because there was no evidence of generalized sympathetic activation (as judged by blood pressure and heart rate changes), the effect may be selective for the renal innervation. PMID:3712279

  5. Tuberous Sclerosis Complex Renal Disease

    PubMed Central

    Dixon, Bradley P.; Hulbert, John C.; Bissler, John J.

    2010-01-01

    Although not as common as other genetic renal diseases such as autosomal dominant polycystic kidney disease, patients with tuberous sclerosis complex frequently have significant renal involvement. Recent revelations in the cell biology of these renal disease manifestations as well as effective therapies for tuberous sclerosis complex-related renal issues have heralded hope of improved renal survival and improved quality of life for the TSC patient. This review specifically addresses some of the major renal manifestations of this disease. PMID:21071977

  6. Effect of chronic accumulation of aluminum on renal function, cortical renal oxidative stress and cortical renal organic anion transport in rats.

    PubMed

    Mahieu, Stella T; Gionotti, Marisa; Millen, Néstor; Elías, María Mónica

    2003-11-01

    The aim of the present work was to study the nephrotoxicity of aluminum lactate administered for 3 months (0.57 mg/100 g bodyweight aluminum, i.p., three times per week) to male Wistar rats. Renal function was studied after 6 weeks of treatment (urine was obtained from rats in metabolic cages) and at the end of the treatment using clearance techniques. Another group of rats was used as kidneys donors at the end of treatment. The renal cortex was separated and homogenized to determine glutathione (GSH) level, glutathione S-transferase (GST) activity and lipid peroxidation (LPO) level. Renal cortex slices were also used to study the p-aminohippuric acid (PAH) accumulation during steady-state conditions and the kinetics of uptake process. Clearance results, at the end of the treatment, indicated that renal functions in treated-rats were not different from those measured in control rats, although the renal concentration parameters differ when they were measured in treated rats after 24 h of food and water deprivation. Balances of water and sodium were also modified at both 1.5 and 3 months of treatment. The activity of alkaline phosphatase (AP) relative to inulin excreted in urine was significantly impaired: controls 2.2+/-0.6 IUI/mg, Al-treated 5.1+/-0.5 IU/mg, P<0.05. These data indicated that proximal tubular cells were loosing apical brush border membranes. Data obtained in cortex homogenates indicated that both GSH and GST activity were significantly decreased, and a significant increase of LPO was noted simultaneously in Al-treated rats. Renal accumulation of PAH, estimated as slice-to-medium ratio, decreased significantly in the Al-treated rats: control rats 3.06+/-0.02 ( n=12), Al-treated rats 2.26+/-0.04 ( n=12), P<0.0001. The maximal rate of uptake was also diminished in treated rats, while the apparent affinity remained unchanged. All these results indicate that aluminum accumulation in renal tissue affects cellular metabolism, promotes oxidative stress and

  7. Clinical effect of Kudiezi injection on renal function based on propensity score.

    PubMed

    Zhang, Zhao-kang; Yang, Wei; Liu, Huan; Zeng, Xian-bin; Zhuang, Yan; Xie, Yan-ming

    2015-07-01

    To explore the effect of Kudiezi injection on renal function in the real world, in order to provide the basis for the clinical medication safety. Patient aged between 18-80 were selected from 18 large hospitals information system (HIS) databases established by clinical research institute for basic traditional Chinese medicine of China academy of Chinese medical sciences. The patients who were treated with Kudiezi injection (24 225 cases) were defined as the exposed group, whereas those who were not treated with Kudiezi injection (14,191 cases) were defined as the non-exposed group. The propensity score method was used to balance the confounding factors. Classic logistic regression, GBM weighted propensity score logistic regression, GBM propensity score weighted logistic regression with covariate and sensitivity analysis were adopted to study the effect of Kudiezi injection on renal function. The results showed no significant difference in the possibility in abnormality in serum creatinine (Scr) (P = 0.940, 0.679, 0.834) and urea nitrogen (BUN) (P = 0, 0.045, 0.164) between both groups. Therefore, the existing data indicated no damage of Kudiezi injection on renal function. Because this study is a retrospective study based on the real world, there may be unknown confounding factors and potential bias. Therefore, further studies shall be conducted to monitor whether Kudiezi injection causes damage on renal function, in order to ensure the clinical medication safety. PMID:26697696

  8. Beneficial effects of nilotinib, tyrosine kinase inhibitor on cyclosporine-A induced renal damage in rats.

    PubMed

    Nader, Manar A; Attia, Ghalia M

    2016-04-01

    Nilotinib is a known tyrosine kinase inhibitor that has been approved for treatment of leukemia. The possible protective effect of nilotinib on cyclosporine A-induced nephropathy was investigated in this study and the possible underlying mechanism was explored. Nilotinib (25mg/kg, orally) and cyclosporine A (15 mg/kg/day, subcutaneous) were given to male SD rats for 28 days. Cyclosporine A alone was found to significantly increase serum creatinine, blood urea nitrogen, lactate dehydrogenase, urinary micrototal protein, renal thiobarbituric acid reactive substance, Bax, cytosol cytochrome c release and nuclear factor kappa B activation. Moreover, cyclosporine A significantly reduced serum albumin, creatinine clearance, urinary total antioxidant, superoxide dismutase, glutathione and Bcl2 protein levels. Pathological results showed that in the model group; there was an obvious shrinkage and congestion of the glomeruli and widening of urinary spaces of renal corpuscles, in addition to marked renal tubular injury and fibrosis, while in the group pretreated with nilotinib all measured serum, renal and pathological changes were significantly reduced. This protective effect of nilotinib is linked to the enhanced antioxidant status and reduced inflammation and apoptosis induced by cyclosporine A. PMID:26844915

  9. Improved effectiveness and safety of flexible ureteroscopy for renal calculi (<2 cm): A retrospective study

    PubMed Central

    Chen, Shuqiu; Xu, Bin; Liu, Ning; Jiang, Hua; Zhang, Xiaowen; Yang, Yu; Liu, Jing; Sha, Guozhu; Zhu, Weidong; Chen, Ming

    2015-01-01

    Introduction: We discuss the efficacy and safety of flexible ureteroscopy for renal calculi with a burden of <2 cm, as well as the prevention and treatment of complications. Methods: A total of 108 renal calculi with flexible ureteroscopy and holmium laser treatment were retrospectively analyzed. The stone-free rate was evaluated. The effectiveness, safety, surgical technique, incidence of complications, and relevant treatments were analyzed. Results: All patients underwent only one lithotripsy procedure. The success rate of flexible ureteroscopy was 97.2% (105/108). Among the 105 cases, the total lithotripsy success rate was 97.1% (101/105). The total stone-free rate after 8 weeks post-operation was 94.3% (99/105), the stone-free rate of the lower calyx was 85.7% (30/35); it was 98.6% (69/70) in the middle–upper calyceal and renal pelvis. The incidence of complications was 12.9% (14/108). None of the patients had serious adverse outcomes. Conclusion: Flexible ureteroscopy represents an optimal treatment option for selected renal calculi with burden of <2 cm. The effectiveness and safety of flexible ureteroscopy can be further improved through reasonable preoperative evaluation and advances in surgical techniques, as well as a better understanding of the inducement and treatment of complications. PMID:26029294

  10. Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats

    PubMed Central

    de Resende, Marco A. C.; Pantoja, Alberto V.; Barcellos, Bruno M.; Reis, Eduardo P.; Consolo, Thays D.; Módolo, Renata P.; Domingues, Maria A. C.; Assad, Alexandra R.; Cavalcanti, Ismar L.; Castiglia, Yara M. M.; Módolo, Norma S. P.

    2015-01-01

    Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model. PMID:26413552

  11. Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

    SciTech Connect

    Mellas, J.; Hammerman, M.R.

    1986-03-01

    We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na/sup +/-H/sup +/ exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using (/sup 14/C)-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 ..gamma.. phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular (Na/sup +/) > intracellular (Na/sup +/), was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na/sup +/-H/sup +/ exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells.

  12. Protective effect of Triphala Rasayana against paracetamol-induced hepato–renal toxicity in mice

    PubMed Central

    Singh, Dewasya Pratap; Mani, Dayanandan

    2015-01-01

    Background: Paracetamol, a widely used analgesic and antipyretic, is known to cause liver and renal injury in humans when administered in higher and repeated doses that cause acute liver injury. Triphala is a well-known Ayurvedic Rasayana formulation that is prescribed for balancing of Vata, Pitta and Kapha. Traditionally, it is used for the treatment of liver and kidney diseases. Objective: The present study was undertaken to examine the protective effect of Triphala extract against paracetamol-induced hepato–renal injury in Swiss albino mice. Materials and Methods: Swiss albino mice (weight 20–25 g) were used in this study. The mice were divided into five groups of six animals each. The aqueous extract of Triphala was given orally at two different doses (100 and 300 mg/kg body weight) for seven consecutive days, followed by a single intraperitoneal injection of paracetamol (500 mg/kg body weight) to induce hepato–renal toxicity. Serum levels of liver enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, creatinine, urea and uric acid were measured as indices of liver and renal injury. All the statistical analyses were performed with the help of one-way analysis of variance (ANOVA) followed by Student–Newman–Keuls test as post hoc test. Results were considered statistically significant when P < 0.05. Results: Pre-treatment with Triphala extract at 100 mg/kg and 300 mg/kg body weight exhibited a significant (P < 0.01) hepatoprotective activity. The protective effect of Triphala extract at 300 mg/kg body weight appears more effective than 100 mg/kg body weight. Conclusion: The present study gives an evidence of the protective role of Triphala extract against paracetamol-induced hepato–renal toxicity and validates its traditional claim in the Ayurveda system. PMID:26604553

  13. The rebirth of interest in renal tubular function.

    PubMed

    Lowenstein, Jerome; Grantham, Jared J

    2016-06-01

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

  14. Protective Effects of Antioxidant Fortified Diet on Renal Function and Metabolic Profile in Obese Zucker Rat

    PubMed Central

    Slyvka, Yuriy; Inman, Sharon R.; Malgor, Ramiro; Jackson, Edwin J.; Yee, Jennifer; Oshogwemoh, Olusayo; Adame, John; Nowak, Felicia V.

    2008-01-01

    Oxidative stress contributes to the pathophysiology of type 2 diabetes mellitus and its complications, including nephropathy. The current study was designed to test the hypothesis that a diet fortified with antioxidants would be beneficial to delay or prevent the progression of this disease. Male and female Zucker fa/fa rats were fed a control or an antioxidant (AO) fortified diet starting at four weeks of age. Metabolic parameters, renal function and renal histopathology were analyzed at 6, 13 and 20 weeks of age. Females on the AO diet had significantly lower blood glucose at 6 and 13 weeks, less severe renal pathology at 20 weeks, and higher glomerular filtration rates (GFR) at 20 weeks than age matched females on the regular diet (p < 0.05). Metabolic parameters including blood glucose, insulin resistance and serum cholesterol, and mean arterial pressure (MAP), worsened with age in both males and females, as expected. GFR decreased and renal pathology also became more severe with age. Finally, females on the AO diet had higher GFRs and lower MAP at 20 weeks than males on the same diet. This may denote a protective effect of the AO diet in females, but not in males. These findings may have implications for the role of antioxidants as therapy in humans with T2DM. PMID:19051067

  15. Effect of paricalcitol and enalapril on renal inflammation/oxidative stress in atherosclerosis

    PubMed Central

    Husain, Kazim; Suarez, Edu; Isidro, Angel; Hernandez, Wilfredo; Ferder, Leon

    2015-01-01

    AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in ApoE-knock out mice. METHODS: Animals treated for 4 mo as group (1) ApoE-knock out plus vehicle, group (2) ApoE-knock out plus paricalcitol (200 ng thrice a week), (3) ApoE-knock out plus enalapril (30 mg/L), (4) ApoE-knock out plus paricalcitol plus enalapril and (5) normal. Blood pressure (BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses. RESULTS: ApoE-deficient mice developed high BP (127 ± 3 mmHg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22phox, manganese-superoxide dismutase, inducible nitric oxide synthase (NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, CuZn-SOD and eNOS levels significantly depleted in ApoE-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in ApoE-knock out animals. CONCLUSION: Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals. PMID:26322179

  16. Inhibitory effects of tetradecanoylphorbol acetate and diacylglycerol on erythropoietin production in human renal carcinoma cell cultures

    SciTech Connect

    Hagiwara, Masamichi; Nagakura, Kazuhiko; Ueno, Munehisa; Fisher, J.W. )

    1987-11-01

    A human renal carcinoma from a patient with an erythrocytosis, serially transplanted into athymic nude mice, was grown in primary monolayer cell cultures. After reaching confluency the cultured cells formed multicellular hemicysts (domes) which became more abundant as the cultures approached saturation density. Erythropoietin (Ep) production by this renal carcinoma in culture was only slightly increased at the time of semiconfluency but showed a marked increase in Ep levels in the culture medium after the cultures reached confluency, in parallel with an increase in dome formation. The phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a significant dose-related inhibitory effect on Ep production and dome formation in the renal carcinoma cell cultures, suggesting an important role of protein kinase C, the only known receptor for TPA, in inhibiting the expression of differentiated phenotypes in the renal carcinoma cells. These studies suggest a role of the inositol-lipid second messenger path and protein kinase C in the regulation of Ep production.

  17. The effects of Ramadan fasting on the number of renal colic visits to the emergency department

    PubMed Central

    Cevik, Yunsur; Corbacioglu, Seref Kerem; Cikrikci, Gulsah; Oncul, Veysel; Emektar, Emine

    2016-01-01

    Objective: The effects of fluid and diet restriction strictly during the long hours in Ramadan on the number of colic visits and biochemical factors of stone formation are controversial in the literature. The aim of this study was to assess the effects of Ramadan fasting on the number of renal colic visits and laboratory results of patients with renal colic. Methods: This was a prospective observational study, which was conducted with patients who were admitted to our emergency department with renal colic. The study period was divided into two parts: Before Ramadan and Ramadan. All laboratory results of patients and daily air temperature values were recorded. p<0.05 was considered statistically significant for all tests. Results: Total 176 patients (n:89 in before Ramadan, n:87 in Ramadan) with renal colic were enrolled into the study. During Ramadan, 49 (73.1%) of 67 patients were admitted in the first half of the month and 20 patients (26.9%) were admitted in the second half of the month. Only urine density and white blood cell values in Ramadan and non-Ramadan period were significantly different (p=0.004 and p=0.001). Hemoglobin, general crystal, and triple phosphate crystal values in the first and the second half of Ramadan were significantly different (p=0.04, p=0.03, and p=0.03). Conclusion: This study has shown that fasting in Ramadan does not change the number of renal colic visits. In addition, although fasting causes some changes in urinary metabolites, there is not enough evidence that these changes increase urinary calculus formation. PMID:27022337

  18. Early effects of renal denervation in the anaesthetised rat: natriuresis and increased cortical blood flow.

    PubMed

    Kompanowska-Jezierska, E; Walkowska, A; Johns, E J; Sadowski, J

    2001-03-01

    A novel method of renal denervation was developed based on electro-coagulation of tissue containing most of the sympathetic fibres travelling towards the kidney. Kidney tissue noradrenaline was decreased to 4.7 % of the content measured in the contralateral innervated kidney when studied 3 days postdenervation. The method was utilised in anaesthetised rats to examine the effects of denervation within the heretofore unexplored first 75 min period postdenervation. Sodium excretion (UNaV) increased significantly (+82 %, P < 0.03) over the 25-50 min after denervation. In a parallel group, with a lower baseline UNaV, there was also a significant increase in UNaV (+54 %, P < 0.03) within the first 25 min. The renal perfusion pressure was maintained at a constant value and the glomerular filtration rate did not change after denervation. Renal cortical and medullary blood flows (CBF, MBF) were estimated as laser Doppler flux and medullary tissue ion concentration was estimated as electrical admittance (Y). Following denervation, in both groups CBF increased significantly within the first 25 min (+12 %, P < 0.01 and +8 %, P < 0.05, respectively) while MBF did not change or decreased slightly; Y did not change. The data document the development of natriuresis within the first 25-50 min after denervation. The increase in CBF indicated that, prior to denervation, the cortical, but not medullary, circulation was under a tonic vasoconstrictor influence of the renal nerves. Such a dissociation of neural effects on the renal cortical vs. medullary vasculature has not been previously described. PMID:11230524

  19. Effects of Long-Term Fenofibrate Treatment on Markers of Renal Function in Type 2 Diabetes

    PubMed Central

    Forsblom, Carol; Hiukka, Anne; Leinonen, Eeva S.; Sundvall, Jouko; Groop, Per-Henrik; Taskinen, Marja-Riitta

    2010-01-01

    OBJECTIVE Although fenofibrate was associated with less progression of albuminuria in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, it is unknown if it has any effect on renal function. We explored if there were changes in commonly available markers of renal function during fenofibrate treatment in the FIELD Helsinki cohort excluding statin users. RESEARCH DESIGN AND METHODS One hundred and seventy subjects with type 2 diabetes were randomly assigned to micronized fenofibrate (200 mg/day) or placebo for 5 years. In this substudy, we measured several markers of albumin excretion and renal function. RESULTS After intensified treatment, blood pressure and fasting glucose decreased in both groups while A1C remained at 7.2%. Plasma creatinine increased with fenofibrate while urine creatinine remained comparable between the groups, resulting in significant decreases in both creatinine clearance and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD)-4 and Cockroft-Gault equations in the fenofibrate group. Cystatin C increased during fenofibrate treatment. Urinary albumin-to-creatinine ratio and diurnal urine protein remained unchanged, whereas overnight urinary albumin excretion rate showed minor decreases in both groups. CONCLUSIONS We report concomitant decreases in creatinine clearance and eGFR by fenofibrate. These changes complicate the clinical surveillance during fenofibrate treatment. We could not demonstrate the beneficial effects of fenofibrate on albumin excretion. A novel finding is the increase of cystatin C in type 2 diabetic patients during fenofibrate treatment. The clinical relevance of the changes needs to be assessed in a long-term outcome study of renal function. PMID:19846798

  20. Early effects of renal denervation in the anaesthetised rat: natriuresis and increased cortical blood flow

    PubMed Central

    Kompanowska-Jezierska, Elzbieta; Walkowska, Agnieszka; Johns, Edward J; Sadowski, Janusz

    2001-01-01

    A novel method of renal denervation was developed based on electro-coagulation of tissue containing most of the sympathetic fibres travelling towards the kidney. Kidney tissue noradrenaline was decreased to 4.7 % of the content measured in the contralateral innervated kidney when studied 3 days postdenervation. The method was utilised in anaesthetised rats to examine the effects of denervation within the heretofore unexplored first 75 min period postdenervation. Sodium excretion (UNaV) increased significantly (+82 %, P < 0.03) over the 25-50 min after denervation. In a parallel group, with a lower baseline UNaV, there was also a significant increase in UNaV (+54 %, P < 0.03) within the first 25 min. The renal perfusion pressure was maintained at a constant value and the glomerular filtration rate did not change after denervation. Renal cortical and medullary blood flows (CBF, MBF) were estimated as laser Doppler flux and medullary tissue ion concentration was estimated as electrical admittance (Y). Following denervation, in both groups CBF increased significantly within the first 25 min (+12 %, P < 0.01 and +8 %, P < 0.05, respectively) while MBF did not change or decreased slightly; Y did not change. The data document the development of natriuresis within the first 25-50 min after denervation. The increase in CBF indicated that, prior to denervation, the cortical, but not medullary, circulation was under a tonic vasoconstrictor influence of the renal nerves. Such a dissociation of neural effects on the renal cortical vs. medullary vasculature has not been previously described. PMID:11230524

  1. Lack of renal tubular and hemodynamic effects of non-selective and delta-opioid receptor antagonism.

    PubMed

    Barrett, R J; Turpin, J A; McGuirk, B A; Kau, S T

    1985-01-01

    The renal pharmacological actions of the non-selective opioid receptor antagonist naloxone and the selective delta (delta)-opioid receptor antagonist ICI 154,129 were examined in conscious dogs. Neither naloxone nor ICI 154,129 altered glomerular filtration rate, renal blood flow, blood pressure, heart rate, or renal excretion of water, Na+, K+, or Cl-. In addition, urine and plasma osmolality and electrolyte concentrations and hematocrit were unchanged, suggesting that neither agent produced physiologically significant alteration in plasma vasopressin levels. These data suggest that (a) naloxone and ICI 154,129 exert no renal pharmacological effects in dogs and (b) under resting physiological conditions, delta-opioid receptors, as well as other opioid receptor subtypes, probably are not involved in the tonic regulation of renal hemodynamics or tubular function. PMID:3983226

  2. Direct renal effects of a fructose-enriched diet: interaction with high salt intake.

    PubMed

    Ares, Gustavo R; Ortiz, Pablo A

    2015-11-01

    Consumption of fructose has increased during the last 50 years. Excessive fructose consumption has a detrimental effect on mammalian health but the mechanisms remain unclear. In humans, a direct relationship exists between dietary intake of added sugars and increased risk for cardiovascular disease mortality (52). While the causes for this are unclear, we recently showed that fructose provided in the drinking water induces a salt-dependent increase in blood pressure in Sprague-Dawley rats in a matter of days (6). However, little is known about the effects of fructose in renal salt handling and whether combined intake of high fructose and salt can lead to salt-sensitive hypertension before the development of metabolic abnormalities. The long-term (more than 4 wk) adverse effects of fructose intake on renal function are not just due to fructose but are also secondary to alterations in metabolism which may have an impact on renal function. This minireview focuses on the acute effect of fructose intake and its effect on salt regulation, as they affect blood pressure. PMID:26447210

  3. Renal-related adverse effects of intravenous contrast media in computed tomography

    PubMed Central

    Leow, Kheng Song; Wu, Yi Wei; Tan, Cher Heng

    2015-01-01

    Renal-related adverse effects of intravascular contrast media (CM) include contrast-induced nephropathy in computed tomography and angiography. While large retrospective studies have been published, the exact pathogenesis of this condition is still unknown. We review the main international guidelines, including the American College of Radiology white paper and the guidelines of European Society of Urogenital Radiology, Royal College of Radiologists and Canadian Association of Radiologists, as well as their references, regarding this subject. We present a simplified, concise approach to renal-related adverse effects of CM, taking into consideration the basis for each recommendation in these published guidelines. This will allow the reader to better understand the rationale behind appropriate patient preparation for cross-sectional imaging. PMID:25917468

  4. Effect of nutritional substrate on sulfolipids metabolic turnover in isolated renal tubules from rat

    PubMed Central

    NAGAI, Ken-ichi; TADANO-ARITOMI, Keiko; NIIMURA, Yukio; ISHIZUKA, Ineo

    2008-01-01

    Effects of a glycolytic (glucose) and a gluconeogenic renal nutritional substrate (glutamine) on metabolic turnover of sulfolipids, determined as [35S]sulfate incorporation, were compared in renal tubules prepared from well-fed rats. The results showed that the effects of glucose and glutamine, at nearly physiological serum concentration, are quite contrary to each other. Glucose increased the turnover rates of relatively long chain ganglio-series sulfoglycolipids (Gg3Cer II3-sulfate and Gg4Cer II3,IV3-bis-sulfate) (1.7 to 2.4-fold), but not of cholesterol 3-sulfate (0.9-fold). In contrast, glutamine accelerated the turnover rates of relatively short chain sulfoglycolipids (glucosyl sulfatide, galactosyl sulfatide and lactosyl sulfatide) (1.3 to 2.7-fold), as well as cholesterol 3-sulfate (2.4-fold). The possible mechanism which causes these marked differences is also discussed. PMID:18941285

  5. The effect of aliskiren on the renal dysfunction following unilateral ureteral obstruction in the rat

    PubMed Central

    Hammad, Fayez T; Lubbad, Loay

    2016-01-01

    Purpose: To investigate the effect of blocking renin-angiotensin system by direct renin inhibition using aliskiren on the renal dysfunction following reversible unilateral ureteral obstruction (UO). Methods: Wistar rats underwent reversible left UO for 72 hours. Group-Alsk (n=12) received aliskiren (30 mg/kg/day) dissolved in water starting one day before creating UO and continued until the terminal experiment five days post reversal when renal functions were measured using clearance techniques. Group-Vx (n=12) underwent similar protocol but had water only. Gene expression analysis of some markers of kidney injury was measured using PCR technique. Results: In Group-Vx, renal blood flow (RBF) and glomerular filtration rate (GFR) in the left kidney were significantly lower than the right kidney (1.82±0.12 vs. 3.19±0.40, P=0.001 and 0.81±0.08 vs. 1.44±0.09, P=0.004, respectively). However, left fractional excretion of sodium (FENa) was higher than the right FENa (0.80±0.15 vs. 0.55±0.04, P=0.05). Comparing the left obstructed kidney in Group-Alsk vs. Group-Vx, RBF and GFR were higher in Group-Alsk (2.44±0.30 vs. 1.82±0.12, P=0.049 and 1.02±0.11 vs. 0.81±0.08, P=0.07, respectively). The left renal FENa was lower in Group-Alsk but did not reach statistical significance (0.54±0.07 vs. 0.80±0.15, P=0.07). Aliskiren also decreased the gene expressions of NGAL, KIM-1 and p53. Conclusion: Direct renin inhibition by aliskiren appears to have protective effect on the renal dysfunction and on the markers of renal injury following UO indicating a potential clinical benefit of this agent. Further, this data and the previous studies indicate that blocking renin-angiotensin system at any level has a protective effect in obstructive nephropathy. PMID:27570581

  6. Purification and renal effects of phospholipase A(2) isolated from Bothrops insularis venom.

    PubMed

    Machado Braga, Marcus Davis; Costa Martins, Alice Maria; Alves, Claudênio Diógenes; de Menezes, Dalgimar Beserra; Martins, René Duarte; Ferreira Barbosa, Paulo Sérgio; de Sousa Oliveira, Isadora Maria; Toyama, Marcos Hikari; Toyama, Daniela Oliveira; Dos Santos Diz Filho, Eduardo Brito; Ramos Fagundes, Fabio Henrique; Fonteles, Manassés Claudino; Azul Monteiro, Helena Serra

    2008-02-01

    Bothrops insularis venom contains a variety of substances presumably responsible for several pharmacological effects. We investigated the biochemical and biological effects of phospholipase A(2) protein isolated from B. insularis venom and the chromatographic profile showed 7 main fractions and the main phospholipase A(2) (PLA(2)) enzymatic activity was detected in fractions IV and V. Fraction IV was submitted to a new chromatographic procedure on ion exchange chromatography, which allowed the elution of 5 main fractions designated as IV-1 to IV-5, from which IV-4 constituted the main fraction. The molecular homogeneity of this fraction was characterized by high-performance liquid chromatography (HPLC) and demonstrated by mass spectrometry (MS), which showed a molecular mass of 13984.20 Da; its N-terminal sequence presented a high amino acid identity (up to 95%) with the PLA(2) of Bothrops jararaca and Bothrops asper. Phospholipase A(2) isolated from B. insularis (Bi PLA(2) ) venom (10 microg/mL) was also studied as to its effect on the renal function of isolated perfused kidneys of Wistar rats (n=6). Bi PLA(2) increased perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF) and glomerular filtration rate (GFR). Sodium (%TNa(+)) and chloride tubular reabsorption (%TCl(-)) decreased at 120 min, without alteration in potassium transport. In conclusion, PLA(2) isolated from B. insularis venom promoted renal alterations in the isolated perfused rat kidney. PMID:17953979

  7. Protective effects of astaxanthin against ischemia/reperfusion induced renal injury in mice.

    PubMed

    Qiu, Xuefeng; Fu, Kai; Zhao, Xiaozhi; Zhang, Yanting; Yuan, Yimin; Zhang, Shiwei; Gu, Xiaoping; Guo, Hongqian

    2015-01-01

    Astaxanthin (ATX) is a powerful antioxidant that occurs naturally in a wide variety of living organisms. Previous studies have shown that ATX has effects of eliminating oxygen free radicals and can protect organs from ischemia/reperfusion (IR) induced injury. The present study was designed to further investigate the protective effects of ATX on oxidative stress induced toxicity in tubular epithelial cells and on IR induced renal injury in mice. ATX, at a concentration of 250 nM, attenuated 100 μM H2O2-inudced viability decrease of tubular epithelial cells. In vivo, ATX preserved renal function 12 h or 24 h post IR. Pretreatment of ATX via oral gavage for 14 consecutive days prior to IR dramatically prevented IR induced histological damage 24 h post IR. Histological results showed that the pathohistological score, number of apoptotic cells, and the expression of α-smooth muscle actin were significantly decreased by pretreatment of ATX. In addition, oxidative stress and inflammation in kidney samples were significantly reduced by ATX 24 h post IR. Taken together, the current study suggests that pretreatment of ATX is effective in preserving renal function and histology via antioxidant activity. PMID:25623758

  8. The effects of blood transfusion on renal functions in orthopaedic surgery

    PubMed Central

    Satoglu, Ismail Safa; Akcay, Serkan; Horoz, Levent; Kaya, Erol; Karakasli, Ahmet; Skiak, Eyad; Basci, Onur

    2015-01-01

    Objective: The effects of perioperative blood transfusion on renal functions have been studied in various studies. In this study, we investigated the effects of blood transfusion on postoperative kidney functions in patients who underwent orthopaedic surgeries. Method: Total 136 patients who were operated for several orthopedic pathologies between June 2013 and December 2014 were evaluated. The patients were divided into two groups according to the amounts of blood transfusion. Ninety five patients (69.8%) who were transfused less than 3 units were included in Group 1 and 41 patients (30.2%) who received 3 and more units of blood were included in Group 2. Results: There were no statistical difference between the two groups in terms of preoperative gender, hypertension, diabetes mellitus, chronical renal failure and smoking habbits (P > 0.05). No statistical differences between the groups were seen in terms of postoperative hospital stay, pulmonary and other complications as well as mortality (P > 0.05). When the two groups were compared for blood parameters showing postoperative renal and other system functions, no statistical differences were detected (P > 0.05). Conclusion: Blood transfusion does not have negative effects on postoperative BUN and creatinine levels in patients operated for orthopaedic pathologies. PMID:26430403

  9. Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles.

    PubMed Central

    Lanese, D M; Conger, J D

    1993-01-01

    Recent evidence suggests that the potent constrictor peptide, endothelin (ET) has a mediating role in cyclosporine A (CsA)-related renal vasoconstriction. However, the nature of the CsA-ET interaction and effect on the renal vasculature is uncertain. The purpose of the present study was twofold: (a) to determine if CsA exposure caused direct local release of ET from the endothelium of the renal microvasculature and (b) to determine if locally generated ET has paracrine effects on the underlying vascular smooth muscle to induce vasoconstriction. Experiments were performed in isolated rat renal arterioles. First it was determined that both afferent arteriole (AA) and efferent arteriole (EA) exhibited concentration-dependent decreases in lumen diameter to increasing molar concentrations of CsA. The AA was more sensitive to the vasoconstrictive effects of CsA than the EA. Next, the blocking effect of a recently synthesized putative ETA receptor antagonist was verified in both the AA and EA, where it was found that the cyclic peptide cyclo D-Asp-L-Pro-D-Val-L-Leu-D-Trp totally inhibited the vasoconstriction observed with ET addition. Finally, the role of locally stimulated ET in CsA-induced vasoconstriction was tested by determining the effect of the ETA receptor antagonist on CsA-induced AA and EA constriction. In the AA the vasoconstrictor effect of 10(-11) M CsA was completely blocked by the ETA receptor antagonist. However, in contrast to AA, 10(-11) M CsA in EA in the presence of the ETA receptor antagonist decreased EA lumen diameter by a mean of 41% from baseline (4.80 +/- 0.75 microns vs 7.80 +/- 0.84 microns, P < 0.05). This change in lumen diameter was similar to that induced by CsA alone. These data suggest that CsA directly constricts renal microvessels. This effect is mediated by ET in the AA but not the EA. PMID:8486781

  10. Effects of Thermodynamic Properties on Slab Evolution

    NASA Astrophysics Data System (ADS)

    Wada, I.; King, S. D.; Caddick, M. J.; Ross, N.

    2012-12-01

    We perform a series of numerical experiments to investigate the effects of thermodynamic properties on the geometrical evolution of subducting slabs. We calculate density (ρ), thermal expansivity (α), and heat capacity (cp) of mantle mineral assemblages of a harzburgite composition over a range of pressure and temperature conditions applicable to the Earth's mantle, using the thermodynamic database of Stixrude and Lithgow-Bertelloni [2011] and the thermodynamic calculation code Perple_X [Connolly, 2009]. Following Nakagawa et al. [2009], we assume that thermal diffusivity (κ) follows a power-law relationship with density (κ=κ0(ρ/ρ0)3, where κ0 and ρ0 are reference diffusivity and density, respectively). The calculations show that ρ, α, and κ change significantly along mantle geotherms; the ranges of their values are 3300-5100 km/m3, 1.5-3.5 10-5/K, and 3-17 W/m K, respectively. The change in cp is small (< 5%). We incorporate the pressure and temperature (PT) dependence of these thermodynamic properties into a 2-D finite element code with compressible convection formulations under the truncated anelastic liquid approximation [Lee and King, 2009] and develop a dynamic subduction model with kinematic boundary conditions. In the model, we use a composite mantle rheology that accounts for both diffusion and dislocation creep with flow law parameterization of wet olivine [Hirth and Kohlstedt, 2003]. Following Billen and Hirth [2007] and Lee and King [2011], we adjust the flow law parameter values for the lower mantle to test the effects of viscosity contrast between the upper and lower mantle on slab evolution. We use a reference model with a constant ρ, κ α, and cp, which is equivalent to using the incompressible extended Bousisnesq approximation. Preliminary results show that incorporating PT-dependent ρ enhances the vigor of the buoyancy driven flow compared to the reference model. Further, lithostatic pressure at a given depth is higher than in the

  11. Effect of trimethoprim on serum creatinine in healthy and chronic renal failure volunteers.

    PubMed

    Myre, S A; McCann, J; First, M R; Cluxton, R J

    1987-06-01

    The effect of trimethoprim (TMP) on serum creatinine concentration (SCr) was studied in 10 healthy (H) subjects and nine subjects with chronic renal failure (CRF). Each volunteer was given TMP 100 mg perorally every 12 h for 10 days followed by a 7-day washout period. SCr was measured colorimetrically immediately before the study (baseline), on day 10 of TMP, and 7 days after TMP had been discontinued. SCr increased an average of 14.8% from baseline during TMP administration in the H volunteers, but this increase was not statistically significant. During TMP administration to the CRF volunteers, a pronounced elevation (34.6%) of mean SCr from baseline was observed (p less than 0.05). SCr returned to baseline values in both groups following the 7-day washout period. These results are consistent with the hypothesis that TMP competitively inhibits the renal tubular secretion of creatinine. PMID:3617154

  12. Effect of enalapril on renal profile and right ventricular dimensions in chronic cor pulmonale.

    PubMed

    Mahajan, S K; Sharma, V K; Thakral, S

    1996-05-01

    The effect of enalapril in combination with bronchodilators, diuretics, antibiotics and/or steroids, was compared with that of conventional treatment with diuretics, steroids and antibiotics alone in 30 patients of chronic cor-pulmonale. The effect was studied on right ventricular dimensions and renal profile after a period of 6 weeks treatment. The control patients showed a significant decrease of RVIDED and increase in GFR, but the decrease of RVAWT and increase of 'a' wave amplitude was insignificant. However when the ACE-inhibitor enalapril was added to the treatment, there was a significant decrease of RVIDED, RVAWT and an increase of 'a' wave amplitude with a significant improvement in the GFR. A comparison between both the groups showed that the increase of GFR and decrease of RVIDED was higher in enalapril group than controls. The increase of 'a' wave amplitude was also greater in enalapril group. Thus enalapril appears to be of value in chronic cor-pulmonale, where it decreases pulmonary hypertension and thus right ventricular after load. It also decreases renal vascular resistance increasing the renal blood flow, thus improving the GFR. PMID:9282581

  13. Effectiveness of low-dose erythropoietin in predialysis chronic renal failure patients.

    PubMed

    Mitwalli, A; Abuaisha, H; al Wakeel, J; al Mohaya, S; Alam, A A; el Gamal, H; Fayed, H

    1993-01-01

    Recombinant human erythropoietin (rHuEpo) has been shown to be both effective and usually safe in patients with chronic renal failure who have not yet reached the stage requiring dialysis. There are, however, disturbing reports on the possibility of deterioration of the reserve renal function in association with rHuEpo therapy. Most of the published studies have used rHuEpo in doses of 50-150 U/kg three times weekly subcutaneously. An open-label trial of rHuEpo therapy was conducted on 21 patients with chronic renal failure treated sequentially at a referral hospital, rHuEpo was used in doses of 50 U/kg twice weekly for 4 weeks followed by 25 U/kg twice weekly for 8 weeks subcutaneously, a regimen substantially lower than current recommendations. This was associated with a gentle but significant increase in haematocrit (P < 0.05) and haemoglobin (P < 0.05), while the serum creatinine and the reciprocal of the creatinine remained stable, with a tendency to improve rather than worsen (P = 0.06). We conclude that there is no need to aim at a rapid increase in haematocrit and haemoglobin by rHuEpo therapy; rather a gentle increase using modest doses is both effective and safe. PMID:8272220

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

    PubMed Central

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

    2015-01-01

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

  15. Nephroprotective Effect of Ursolic Acid in a Murine Model of Gentamicin-Induced Renal Damage

    PubMed Central

    Pai, Preethi G.; Chamari Nawarathna, Savindika; Kulkarni, Avdhooth; Habeeba, Umma; Reddy C., Sudarshan; Teerthanath, Srinivas; Shenoy, Jnaneshwara P.

    2012-01-01

    The present study evaluates the nephroprotective effects of ursolic acid in a murine model of gentamicin induced renal damage. Wistar albino rats of either sex, weighing 150–200 g were divided into 5 groups; normal saline, gentamicin 80 mg/kg, intraperitoneally for 8 days, ursolic acid at 2, 5, and 10 mg/kg, per oral for 8 days, ursolic acid administered 3 days prior and concurrently with gentamicin for 5 days. Blood urea, serum creatinine, uric acid and blood urea nitrogen analyses and microscopic examination of kidney were performed. Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in serum urea, serum uric acid, serum creatinine and blood urea nitrogen (162.33 ± 9.92 mg/dL, 3.13 ± 0.12 mg/dL, 6.85 ± 0.35 mg/dL and 75.86 ± 4.64 mg/dL; resp.) when compared to the saline treated groups. Co-administration of ursolic acid with gentamicin decreased the rise in these parameters in a dose dependent manner. Histopathological analysis revealed epithelial loss with intense granular degeneration in gentamicin treated rats, whereas ursolic acid mitigated the severity of gentamicin-induced renal damage. To conclude, our data suggest that ursolic acid exhibits renoprotective effect in gentamicin induced renal damage and further studies on its mechanis of action are warranted. PMID:22811930

  16. Cost-effectiveness of kidney transplantation compared with chronic dialysis in end-stage renal disease.

    PubMed

    Rosselli, Diego; Rueda, Juan-David; Diaz, Carlos Eduardo

    2015-01-01

    To estimate the costs and effectiveness measured in quality-adjusted life years (QALY) of kidney transplantation compared with dialysis in adults suffering from end-stage renal disease from the perspective of the Colombian healthcare system, we designed a Markov model with monthly cycles over a five-year time horizon and eight transitional states, including death as an absorbing state. Transition probabilities were obtained from international registries, costs from different local sources [case studies, official tariffs (ISS 2001 + 35%) for procedures and SISMED for medications]. Data were validated by an expert panel and we performed univariate, multivariate and probabilistic sensitivity analyses. Effectiveness indicators were months of life gained, months of dialysis averted and deaths prevented. The annual discount rate was 3% and the cost-utility threshold (willingness to pay) was three times gross domestic product (GDP) = USD 20,000 per QALY. The costs were adopted in US dollars (USD) using the 2012 average exchange rate (1 USD = COP$ 1798). The discounted average total cost for five years was USD 76,718 for transplantation and USD 76,891 for dialysis, with utilities 2.98 and 2.10 QALY, respectively. Additionally, renal transplantation represented 6.9 months gained, 35 months in dialysis averted per patient and one death averted for each of the five patients transplanted in five years. We conclude that renal transplantation improves the overall survival rates and quality of life and is a cost-saving alternative compared with dialysis. PMID:26178546

  17. Effect of renal impairment and haemodialysis on the pharmacokinetics of gemigliptin (LC15-0444).

    PubMed

    Shon, J H; Kim, N; Park, S J; Oh, M K; Kim, E Y; Lee, S H; Kim, Y H; Shin, J G

    2014-10-01

    This study evaluated the effects of renal impairment (RI) and haemodialysis (HD) on the pharmacokinetics of gemigliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor. After a 100 mg administration to subjects with normal renal function (n = 23) or RI (n = 24), plasma, urine or dialysate samples were analysed. Control subjects were matched to patients based on age, gender and body mass index. Patients with mild, moderate, severe RI and end-stage renal disease (ESRD) showed 1.20, 2.04, 1.50 and 1.66-fold (1.10, 1.49, 1.22 and 1.21-fold) increase of mean area under the time-plasma concentration curve from 0 to infinity (AUCinf) [maximum plasma concentration (Cmax)] of gemigliptin, respectively. Pharmacokinetics of gemigliptin was comparable between HD and non-HD periods in ESRD patients. Less than 4% of the dose was removed by 4 h HD. RI appeared to have modest effect on the gemigliptin disposition. No dose adjustment in patients with RI is proposed on the basis of exposure-response relationship. Impact of HD on the removal of gemigliptin was negligible. PMID:24641348

  18. Effect of stevioside on PAH transport by isolated perfused rabbit renal proximal tubule.

    PubMed

    Jutabha, P; Toskulkao, C; Chatsudthipong, V

    2000-09-01

    Stevioside, a non-caloric sweetening agent, is used as a sugar substitute. An influence of stevioside on renal function has been suggested, but little is known about its effect on tubular function. Therefore, the present study was designed to explore the direct effect of stevioside on transepithelial transport of p-aminohippurate (PAH) in isolated S2 segments of rabbit proximal renal tubules using in vitro microperfusion. Addition of stevioside at a concentration of 0.45 mM to either the tubular lumen, bathing medium, or both at the same time had no effect on transepithelial transport of PAH. Similarly, a concentration of 0.70 mM (maximum solubility in the buffer) when present in the lumen, had no effect on PAH transport. However, this concentration in the bathing medium inhibited PAH transport significantly by about 25-35%. The inhibitory effect of stevioside was gradually abolished after it was removed from the bath. Addition of 0.70 mM stevioside to both lumen and bathing medium at the same time produced no added inhibitory effect. Stevioside at this concentration has no effect on Na+/K+-ATPase activity as well as cell ATP content. These findings suggest that stevioside, at a pharmacological concentration of 0.70 mM, inhibits transepithelial transport of PAH by interfering with the basolateral entry step, the rate-limiting step for transepithelial transport. The lack of effect of stevioside on transepithelial transport of PAH on the luminal side and its reversible inhibitory effect on the basolateral side indicate that stevioside does not permanently change PAH transport and should not harm renal tubular function at normal human intake levels. PMID:11007537

  19. Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents.

    PubMed

    Fortuny, Clàudia; Deyà-Martínez, Ángela; Chiappini, Elena; Galli, Luisa; de Martino, Maurizio; Noguera-Julian, Antoni

    2015-05-01

    Worldwide, the benefits of combined antiretroviral (ARV) therapy in morbidity and mortality due to perinatally acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to ARV treatment. The other metabolic comorbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit nonsymptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the third and fourth decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts' consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of ARV options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more ARV drugs have proved useful. Specific therapies are also available for some of these comorbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically HIV-infected children and adolescents. PMID:25629891

  20. Effect of chronic poisoning with aluminum on the renal handling of phosphate in the rat.

    PubMed

    Mahieu, S; Calvo, M L

    1998-01-16

    The effects of aluminum on renal function and phosphate handling were studied using clearance techniques in chronically-intoxicated rats. Rats were given aluminum hydroxide (80 mg/kg b.w., i.p.), three times per week during 6 months. The phosphate tubular transport capacity was evaluated by determining the maximum tubular transport (TmRPi) and the fractional excretion of phosphate (FE% Pi) during the infusion of phosphate solutions with increasing concentrations (0, 9, 18, 33 mM). Parathyroid gland function was studied using indirect methods: calcemia recovery after EDTA administration and the nephrogenic excretion of cAMP as indicative of renal PTH actions, by RIA. The systemic acid base status was determined and food intake and rat growth were controlled in both groups. No changes were observed in the renal function. Pi reabsorption values per ml glomerular filtration rate (TRPi/GFR microg/ml) for different Pi plasmatic concentrations were distributed following a saturation curve compatible with a saturation kinetics. Aluminum increased TmRPi/GFR in treated animals (T) 76+/-4 as compared with control animals (C) 57+/-7 microg/ml, without a statistical modification in the apparent affinity. The FE% Pi and FE% Na were significantly lower in treated animals than in control animals. There were neither systemic variations in the acid-base balance nor in the Ca and Pi concentrations in plasma. The calcemia recovery following a hypocalcemic stimulus and the nephrogenic excretion of cAMP (T: 44+/-4; C: 91+/-7 pmol/min) were diminished. Considering all these facts, it can be postulated that the aluminum renal effect is associated from a decrease in PTH phosphaturic capacity. Nevertheless, other associated factors like minor phosphate intestinal absorption rate may not be disregarded, even though there were no significant intake variations. PMID:9544698

  1. Effects of opioids on proximal renal tubular cells undergoing ATP depletion.

    PubMed

    Bellini, Luca; Vadori, Marta; De Benedictis, Giulia Maria; Busetto, Roberto

    2016-08-01

    This study investigated the effect of morphine, fentanyl, butorphanol and buprenorphine on viability and caspase-3 activity in renal proximal tubular cells exposed to opioids for 2 h before or 12 h after chemical anoxia. Cell viability decreased regardless the treatment although intracellular ATP content was elevated in morphine and fentanyl pre-treated cells at 12 h. Anoxia increased caspase activity but this effect was significantly reduced in cells treated before or after with morphine, fentanyl and in cell treated with butorphanol for 12 h. No influence of buprenorphine was detected. Morphine, fentanyl and butorphanol might have protective effects during kidney ischemia. PMID:27569459

  2. [The effect of aldosterone A on renal potassium excretion].

    PubMed

    Winther, Signe Abitz; Egfjord, Martin

    2011-01-10

    Recent studies have shown expression of the following regulatory WNK kinases in the kidney: the full-length WNK1 (L-WNK1), the shorter kidney specific WNK1 transcript (KS-WNK1), formed by alternative splicing, and WNK4. Aldosterone activates expression of KS-WNK1 and inhibits WNK4 via SGK1 - both leading to stimulation of ENaC and activation of ROMK, and increased potassium excretion. Thus, further characterization of the WNK system may lead to elucidation of the dual anti-natriuretic and kaliuretic effects of aldosterone, in situations where only activation of one of these effects is needed. PMID:21219845

  3. Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease.

    PubMed

    Ritz, E; Benck, U; Franek, E; Keller, C; Seyfarth, M; Clorius, J

    1998-10-01

    Patients with renal disease who smoke have a poor renal functional prognosis, but the mechanisms involved have not been explored. In this controlled study, the effects of smoking and sham smoking were compared in 15 healthy normotensive volunteers. All were occasional smokers and abstained from smoking for 48 h as documented by urinary cotinine measurements. These data were compared with those of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional smokers. Renal clearance examinations were obtained after hydration in the supine position before and while smoking two cigarettes or sham cigarettes in random order on 2 consecutive days. GFR and effective renal plasma flow were determined using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual tracer infusion clearance technique. In an ancillary study with six volunteers, the effect of smoking was compared with the effect of nicotine-containing chewing gum. In healthy volunteers, sham smoking caused a minor but significant increase of mean arterial pressure (MAP) and GFR with no significant change of effective renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98 to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)), accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72 to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3 ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were reproduced with nicotine-containing chewing gum. In contrast, when patients with IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes of

  4. Role of ATP-dependent K channels in the effects of erythropoietin in renal ischaemia injury

    PubMed Central

    Yilmaz, Tonguç Utku; Yazihan, Nuray; Dalgic, Aydın; Kaya, Ezgi Ermis; Salman, Bulent; Kocak, Mehtap; Akcil, Ethem

    2015-01-01

    Background & objectives: Erythropoietin (EPO) has cytoprotective and anti-apoptotic effects in pathological conditions, including hypoxia and ischaemia-reperfusion injury. One of the targets to protect against injury is ATP-dependent potassium (KATP) channels. These channels could be involved in EPO induced ischaemic preconditoning like a protective effect. We evaluated the cell cytoprotective effects of EPO in relation to KATP channel activation in the renal tubular cell culture model under hypoxic/normoxic conditions. Methods: Dose and time dependent effects of EPO, KATP channel blocker glibenclamide and KATP channel opener diazoxide on cellular proliferation were evaluated by colorimetric assay MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] under normoxic and hypoxic conditions in human renal proximal tubular cell line (CRL-2830). Evaluation of the dose and time dependent effects of EPO, glibenclamide and diazoxide on apoptosis was done by caspase-3 activity levels. Hypoxia inducible factor-1 alpha (HIF-1 α) mRNA levels were measured by semi-quantative reverse transcription polymerase chain reaction (RT)-PCR. Kir 6.1 protein expresion was evalutaed by Western blot. Results: Glibenclamide treatment decreased the number of living cells in a time and dose dependent manner, whereas EPO and diazoxide treatments increased. Glibenclamide (100 μM) treatment significantly blocked the anti-apoptotic effects of EPO (10 IU/ml) under both normoxic and hypoxic conditions. EPO (10 IU/ml) and diazoxide (100 μM) treatments significantly increased (P<0.01) whereas glibenclamide decreased (P<0.05) HIF-1 α mRNA expression. Glibenclamide significantly (P<0.01) decreased EPO induced HIF-1 α mRNA expression when compared with the EPO alone group. Interpretation & conclusions: Our results showed that the cell proliferative, cytoprotective and anti-apoptotic effects of EPO were associated with KATP channels in the renal tubular cell culture model under hypoxic

  5. Protective effects of Ficus racemosa stem bark against doxorubucin-induced renal and testicular toxicity

    PubMed Central

    Ahmed, Faiyaz; Urooj, Asna; Karim, Alias A.

    2013-01-01

    Background: Ficus racemosa Linn. (Moraceae) bark is a rich source of phenolic compounds known to possess potential antioxidant activity offering numerous health benefits. Materials and Methods: The present study evaluated the protective effects of sequential acetone extract of Ficus racemosa bark at two doses (FR250; 250 mg kg-1 and FR500; 500 mg kg-1 p.o.) against doxorubicin-induced renal and testicular toxicity in rats. Results: Doxorubicin administration resulted in significant decrease (P ≤ 0.05) in total protein and glutathione concentrations, while increased (P ≤ 0.05) serum urea, creatinine and thiobarbituric acid reactive substances (TBARS). Extract pretreatment restored biochemical parameters toward normalization. FR250 and FR500 decreased serum creatinine levels by 22.5% and 44%, while serum urea levels were decreased by 30.4% and 58.8%, respectively. Extract pretreatment (500 mg kg-1) decreased TBARS and increased glutathione levels in the kidney and testis to control levels. These observations were substantiated by histopathological studies, wherein normal renal and testicular architecture was restored in FR500 group. Conclusion: Doxorubicin exposure results in pronounced oxidative stress, and administration of F. racemosa stem bark extract offers significant renal and testicular protection by inhibiting lipidperoxidation-mediated through scavenging free radicals. PMID:23772108

  6. Protective effect of crocetin on hemorrhagic shock-induced acute renal failure in rats.

    PubMed

    Wang, Yunbo; Yan, Junling; Xi, Liang; Qian, Zhiyu; Wang, Zhenghong; Yang, Lina

    2012-07-01

    Multiple organ failure is a common outcome of hemorrhagic shock followed by resuscitation, and the kidney is one of the prime target organs involved. The main objective of the study was to evaluate whether crocetin, a natural product from Gardenia jasminoides Ellis, has beneficial effects on renal dysfunction caused by hemorrhagic shock and resuscitation in rats. Anesthetized rats were bled to reduce mean arterial blood pressure to 35 (SD, 5) mmHg for 60 min and then were resuscitated with their withdrawn shed blood and normal saline. Crocetin was administered via the duodenum at a dose of 50 mg/kg 40 min after hemorrhage. The increase in creatinine and blood urea nitrogen was significantly reduced at 2 h after hemorrhage and resuscitation in crocetin-treated rats. The increases in renal nitric oxide, tumor necrosis factor α, and interleukin 6 were also attenuated by crocetin. Hemorrhagic shock resulted in a significant elevation in malondialdehyde production and was accompanied by a reduction in total superoxide dismutase activity, activation of nuclear factor κB, and overexpression of inducible nitric oxide synthase. These changes were significantly attenuated by crocetin at 2 h after resuscitation. These results suggested that crocetin blocks inflammatory cascades by inhibiting production of reactive oxygen species and restoring superoxide dismutase activity to ameliorate renal dysfunction caused by hemorrhage shock and resuscitation. PMID:22576007

  7. The effective bioengineering method of implantation decellularized renal extracellular matrix scaffolds

    PubMed Central

    Guan, Yong; Liu, Shuangde; Sun, Chao; Cheng, Guanghui; Kong, Feng; Luan, Yun; Xie, Xiaoshuai; Zhao, Shengtian; Zhang, Denglu; Wang, Jue; Li, Kailin; Liu, Yuqiang

    2015-01-01

    End stage renal disease (ESRD) is a progressive loss of kidney function with a high rate of morbidity and mortality. Transplantable organs are hard to come by and hold a high risk of recipient immune rejection. We intended to establish a more effective and faster method to decellularize and recellularize the kidney scaffold for transplant and regeneration. We successfully produced renal scaffolds by decellularizing rat kidneys with 0.5% sodium dodecyl sulfate (SDS), while still preserving the extracellular matrix (ECM) 3D architecture, an intact vascular tree and biochemical components. We recellularized the kidney scaffolds with mouse embryonic stem (ES) cells that then populated and proliferated within the glomerular, vascular, and tubular structures. After in vivo implantation, these recellularized scaffolds were easily reperfused, tolerated blood pressure and produced urine with no blood leakage. Our methods can successfully decellularize and recellularize rat kidneys to produce functional renal ECM scaffolds. These scaffolds maintain their basic components, retain intact vasculature and show promise for kidney regeneration. PMID:26418881

  8. The effect of ONCE Renal on minerals and electrolytes in predialysis patients with chronic kidney disease

    PubMed Central

    Satirapoj, Bancha; Prapakorn, Janjira; Punpanich, Dollapas; Pongsuparbchon, Chantima; Supasyndh, Ouppatham

    2016-01-01

    Background Malnutrition is one common adverse consequence in patients with advanced chronic kidney disease (CKD), and most patients have a lower-than-normal dietary energy intake. The present study was undertaken to examine whether orally administered ONCE Renal formula (ORF) supplement would improve energy intake without minerals and electrolytes disturbances in predialysis patients with CKD. Methods All eligible nondiabetic patients with CKD received ORF supplement for 1 week. Nutrition markers, renal function, and minerals and electrolytes were evaluated before and after supplementing. All patients kept a 3-day food record and were interviewed by a registered dietitian. Results A total of 29 patients with mean age 64.9±13.3 years were included. Mean estimated glomerular filtration rate was 37.7±12.1 mL/min/1.73 m2. A significant increase was observed in amount of energy, fat, fiber, calcium, and magnesium intake after 1 week of ORF supplement. Moreover, in comparison with baseline values, the patients displayed decreased dietary protein intake and blood urea nitrogen and increased serum magnesium. However, no significant change was found in renal function, nutritional markers (body weight, prealbumin, albumin, and protein equivalence of total nitrogen appearance), serum calcium, phosphorus, sodium, potassium, and bicarbonate. Conclusion In patients with CKD, ingestion of ORF was well tolerated and had a positive effect with an increase in dietary energy, fat, and fiber intake, as well as a decreased dietary protein intake. No mineral or electrolyte abnormalities were observed during the study. PMID:27103839

  9. Volcanic aerosols: Chemistry, evolution, and effects

    NASA Technical Reports Server (NTRS)

    Turco, Richard

    1991-01-01

    Stratospheric aerosols have been the subject of scientific speculation since the 1880s, when the powerful eruption of Krakatoa attracted worldwide attention to the upper atmosphere through spectacular optical displays. The presence of a permanent tenuous dust layer in the lower stratosphere was postulated in the 1920s following studies of the twilight glow. Junge collected the first samples of these 'dust' particles and demonstrated that they were actually composed of sulfates, most likely concentrated sulfuric acid (Junge and Manson, 1961; Junge, 1963). Subsequent research has been spurred by the realization that stratospheric particles can influence the surface climate of earth through their effects on atmospheric radiation. Such aerosols can also influence, through chemical and physical effects, the trace composition of the atmosphere, ozone concentrations, and atmospheric electrical properties. The properties of stratospheric aerosols (both the background particles and those enhanced by volcanic eruptions) were measured in situ by balloon ascents and high altitude aircraft sorties. The aerosols were also observed remotely from the ground and from satellites using both active (lidar) and passive (solar occultation) techniques (remote sensing instruments were carried on aircraft and balloon platforms as well). In connection with the experimental work, models were developed to test theories of particle formation and evolution, to guide measurement strategies, to provide a means of connecting laboratory and field data, and to apply the knowledge gained to answer practical questions about global changes in climate, depletion of the ozone layer, and related environmental problems.

  10. Effects of tempol on altered metabolism and renal vascular responsiveness in fructose-fed rats.

    PubMed

    Abdulla, Mohammed H; Sattar, Munavvar A; Johns, Edward J

    2016-02-01

    This study investigated the effect of tempol (a superoxide dismutase mimetic) on renal vasoconstrictor responses to angiotensin II (Ang II) and adrenergic agonists in fructose-fed Sprague-Dawley rats (a model of metabolic syndrome). Rats were fed 20% fructose in drinking water (F) for 8 weeks. One fructose-fed group received tempol (FT) at 1 mmol·L(-1) in drinking water for 8 weeks or as an infusion (1.5 mg·kg(-1)·min(-1)) intrarenally. At the end of the treatment regimen, the renal responses to noradrenaline, phenylephrine, methoxamine, and Ang II were determined. F rats exhibited hyperinsulinemia, hyperuricemia, hypertriglyceridemia, and hypertension. Tempol reduced blood glucose and insulin levels (all p < 0.05) in FT rats compared with their untreated counterparts. The vasoconstriction response to all agonists was lower in F rats than in control rats by about 35%-65% (all p < 0.05). Vasoconstrictor responses to noradrenaline, phenylephrine, and methoxamine but not Ang II were about 41%-75% higher in FT rats compared with F rats (all p < 0.05). Acute tempol infusion blunted responses to noradrenaline, methoxamine, and Ang II in control rats by 32%, 33%, and 62%, while it blunted responses to noradrenaline and Ang II in F rats by 26% and 32%, respectively (all p < 0.05), compared with their untreated counterparts. Superoxide radicals play a crucial role in controlling renal vascular responses to adrenergic agonists in insulin-resistant rats. Chronic but not acute tempol treatment enhances renal vascular responsiveness in fructose-fed rats. PMID:26789093

  11. The effect of continuous versus intermittent renal replacement therapy on the outcome of critically ill patients with acute renal failure (CONVINT): a prospective randomized controlled trial

    PubMed Central

    2014-01-01

    Introduction Acute renal failure (ARF) requiring renal replacement therapy (RRT) occurs frequently in ICU patients and significantly affects mortality rates. Previously, few large clinical trials investigated the impact of RRT modalities on patient outcomes. Here we investigated the effect of two major RRT strategies (intermittent hemodialysis (IHD) and continuous veno-venous hemofiltration (CVVH)) on mortality and renal-related outcome measures. Methods This single-center prospective randomized controlled trial (“CONVINT”) included 252 critically ill patients (159 male; mean age, 61.5 ± 13.9 years; Acute Physiology and Chronic Health Evaluation (APACHE) II score, 28.6 ± 8.8) with dialysis-dependent ARF treated in the ICUs of a tertiary care academic center. Patients were randomized to receive either daily IHD or CVVH. The primary outcome measure was survival at 14 days after the end of RRT. Secondary outcome measures included 30-day-, intensive care unit-, and intrahospital mortality, as well as course of disease severity/biomarkers and need for organ-support therapy. Results At baseline, no differences in disease severity, distributions of age and gender, or suspected reasons for acute renal failure were observed. Survival rates at 14 days after RRT were 39.5% (IHD) versus 43.9% (CVVH) (odds ratio (OR), 0.84; 95% confidence interval (CI), 0.49 to 1.41; P = 0.50). 14-day-, 30-day, and all-cause intrahospital mortality rates were not different between the two groups (all P > 0.5). No differences were observed in days on RRT, vasopressor days, days on ventilator, or ICU-/intrahospital length of stay. Conclusions In a monocentric RCT, we observed no statistically significant differences between the investigated treatment modalities regarding mortality, renal-related outcome measures, or survival at 14 days after RRT. Our findings add to mounting data demonstrating that intermittent and continuous RRTs may be considered equivalent approaches

  12. Protective Effects of Tinospora crispa Stem Extract on Renal Damage and Hemolysis during Plasmodium berghei Infection in Mice

    PubMed Central

    Nutham, Narain; Sakulmettatham, Sakuna; Klongthalay, Suwit; Chutoam, Palatip; Somsak, Voravuth

    2015-01-01

    Renal damage and hemolysis induced by malaria are associated with mortality in adult patients. It has been speculated that oxidative stress condition induced by malaria infection is involved in its pathology. Thus, we aimed to investigate the protective effects of Tinospora crispa stem extract on renal damage and hemolysis during Plasmodium berghei infection. T. crispa stem extract was prepared using hot water method and used for oral treatment in mice. Groups of ICR mice were infected with 1 × 107 parasitized erythrocytes of P. berghei ANKA by intraperitoneal injection and given the extracts (500, 1000, and 2000 mg/kg) twice a day for 4 consecutive days. To assess renal damage and hemolysis, blood urea nitrogen (BUN), creatinine, and hematocrit (%Hct) levels were then evaluated, respectively. Malaria infection resulted in renal damage and hemolysis as indicated by increasing of BUN and creatinine and decreasing of %Hct, respectively. However, protective effects on renal damage and hemolysis were observed in infected mice treated with these extracts at doses of 1000 and 2000 mg/kg. In conclusion, T. crispa stem extract exerted protective effects on renal damage and hemolysis induced by malaria infection. This plant may work as potential source in the development of variety of herbal formulations for malarial treatment. PMID:26600953

  13. Protective Effects of Tinospora crispa Stem Extract on Renal Damage and Hemolysis during Plasmodium berghei Infection in Mice.

    PubMed

    Nutham, Narain; Sakulmettatham, Sakuna; Klongthalay, Suwit; Chutoam, Palatip; Somsak, Voravuth

    2015-01-01

    Renal damage and hemolysis induced by malaria are associated with mortality in adult patients. It has been speculated that oxidative stress condition induced by malaria infection is involved in its pathology. Thus, we aimed to investigate the protective effects of Tinospora crispa stem extract on renal damage and hemolysis during Plasmodium berghei infection. T. crispa stem extract was prepared using hot water method and used for oral treatment in mice. Groups of ICR mice were infected with 1 × 10(7) parasitized erythrocytes of P. berghei ANKA by intraperitoneal injection and given the extracts (500, 1000, and 2000 mg/kg) twice a day for 4 consecutive days. To assess renal damage and hemolysis, blood urea nitrogen (BUN), creatinine, and hematocrit (%Hct) levels were then evaluated, respectively. Malaria infection resulted in renal damage and hemolysis as indicated by increasing of BUN and creatinine and decreasing of %Hct, respectively. However, protective effects on renal damage and hemolysis were observed in infected mice treated with these extracts at doses of 1000 and 2000 mg/kg. In conclusion, T. crispa stem extract exerted protective effects on renal damage and hemolysis induced by malaria infection. This plant may work as potential source in the development of variety of herbal formulations for malarial treatment. PMID:26600953

  14. Renal handling of drugs in renal failure. I: Differential effects of uranyl nitrate- and glycerol-induced acute renal failure on renal excretion of TEAB and PAH in rats

    SciTech Connect

    Lin, J.H.; Lin, T.H.

    1988-09-01

    Two etiologically different models of experimental acute renal failure were induced in rats by administration of either glycerol or uranyl nitrate. Both compounds caused a substantial decrease in the glomerular filtration rate (GFR) and the net tubular secretion of tetraethylammonium bromide (TEAB) and para-aminohippuric acid (PAH). The degree of renal impairment induced by uranyl nitrate and glycerol appeared to be dose related. Deprivation of drinking water 24 hr before the administration of glycerol potentiated the renal damage. In uranyl nitrate-induced renal failure, the decline of the net tubular secretion for TEAB and PAH was not proportional to the decrease in GFR; the secretion process deteriorated faster than the GFR. For example, when 0.5 mg/kg uranyl nitrate was administered, GFR fell to approximately 65% of normal, whereas the net tubular secretion was decreased to 30% of normal. These results suggest that the tubular transport was preferentially affected by uranyl nitrate. In contrast, in glycerol-induced renal failure, the decline of TEAB secretion fell in a parallel fashion with the GFR, suggesting that the glomeruli and the proximal tubules were equally damaged by glycerol. However, in this latter model, the decline of PAH secretion did not parallel the decrease in GFR, contradicting the proposal that glycerol affects equally the glomeruli and the proximal tubules. This discrepancy may be due to the selective competitive inhibition of PAH secretion by the accumulation of naturally occurring organic acids.

  15. Radiation-induced renal damage: the effects of hyperfractionation. [Mice

    SciTech Connect

    Stewart, F.A.; Soranson, J.A.; Alpen, E.L.; Williams, M.V.; Denekamp, J.

    1984-05-01

    The response of mouse kidneys to multifraction irradiation was assessed using three nondestructive functional end points. A series of schedules was investigated giving 1, 2, 4, 8, 16, 32, or 64 equal X-ray doses, using doses per fraction in the range of 0.9 to 16 Gy. The overall treatment time was kept constant at 3 weeks. Kidney function was assessed from 19 to 48 weeks after irradiation by measuring changes in isotope clearance, urine output, and hematocrit. All three assays yielded steep dose-effect curves from which the repair capacity of kidney could be estimated by comparing the isoeffective doses in different schedules. There was a marked influence of fractionation, with increasing dose being required to achieve the same level of damage for increasing fraction number, even between 32 and 64 fractions. The data are well fitted by a linear quadratic dose-response equation, and analysis of the data would suggest that hyperfractionation, using extremely small X-ray doses per fraction, would spare kidneys relative to tumors and acutely responding tissues.

  16. Involvement of Cyclic Guanosine Monophosphate-Dependent Protein Kinase I in Renal Antifibrotic Effects of Serelaxin

    PubMed Central

    Wetzl, Veronika; Schinner, Elisabeth; Kees, Frieder; Hofmann, Franz; Faerber, Lothar; Schlossmann, Jens

    2016-01-01

    Introduction: Kidney fibrosis has shown to be ameliorated through the involvement of cyclic guanosine monophosphate (cGMP) and its dependent protein kinase I (cGKI). Serelaxin, the recombinant form of human relaxin-II, increases cGMP levels and has shown beneficial effects on kidney function in acute heart failure patients. Antifibrotic properties of serelaxin are supposed to be mediated via relaxin family peptide receptor 1 and subsequently enhanced nitric oxide/cGMP to inhibit transforming growth factor-β (TGF-β) signaling. This study examines the involvement of cGKI in the antifibrotic signaling of serelaxin. Methods and Results: Kidney fibrosis was induced by unilateral ureteral obstruction in wildtype (WT) and cGKI knock-out (KO) mice. After 7 days, renal antifibrotic effects of serelaxin were assessed. Serelaxin treatment for 7 days significantly increased cGMP in the kidney of WT and cGKI-KO. In WT, renal fibrosis was reduced through decreased accumulation of collagen1A1, total collagen, and fibronectin. The profibrotic connective tissue growth factor as well as myofibroblast differentiation were reduced and matrix metalloproteinases-2 and -9 were positively modulated after treatment. Moreover, Smad2 as well as extracellular signal-regulated kinase 1 (ERK1) phosphorylation were decreased, whereas phosphodiesterase (PDE) 5a phosphorylation was increased. However, these effects were not observed in cGKI-KO. Conclusion: Antifibrotic renal effects of serelaxin are mediated via cGMP/cGKI to inhibit Smad2- and ERK1-dependent TGF-β signaling and increased PDE5a phosphorylation. PMID:27462268

  17. Human effects on estuarine shoreline decadal evolution

    NASA Astrophysics Data System (ADS)

    Rilo, A.; Freire, P.; Ceia, R.; Mendes, R. N.; Catalão, J.; Taborda, R.

    2012-04-01

    Due to their sheltered conditions and natural resources, estuaries were always attractive to human activities (industrial, agriculture, residential and recreation). Consequently, the complex interactions between anthropogenic and natural drivers increase estuarine shoreline vulnerability to climate changes impacts. The environmental sustainability of these systems depends on a fragile balance between societal development and natural values that can be further disturbed by climate change effects. This challenging task for scientific community, managers and stakeholders can only be accomplished with interdisplinary approaches. In this context, it seems clear that estuarine management plans should incorporate the concept of change into the planning of policy decisions since these natural dynamic areas are often under human pressure and are recognized as sensitive to climate change effects. Therefore, the knowledge about historical evolution of estuarine shoreline is important to provide new insights on the spatial and temporal dimensions of estuarine change. This paper aims to present and discuss shoreline changes due to human intervention in Tagus estuary, located on the west coast of Portugal. Detailed margins cartography, in a 550m fringe (drawn inland from the highest astronomical tide line), was performed based on 2007 orthophotos (spatial resolution of 0.5 m) analysis. Several classification categories were considered, as urbanized areas, industrial, port and airport facilities, agriculture spaces, green areas and natural zones. The estuarine bed (area bellow the highest astronomical tide line) was also mapped (including human occupation, natural habitats, morpho-sedimentary units) based on the geographic information above and LANSAT 7 TM+ images using image processing techniques. Aerial photographs dated from 1944, 1946, 1948, 1955 and 1958 were analyzed for a set of pilot zones in order to fully understand the decadal shoreline change. Estuarine bed presents

  18. Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats

    PubMed Central

    Berger, Rebeca Caldeira Machado; Vassallo, Paula Frizera; Crajoinas, Renato de Oliveira; Oliveira, Marilene Luzia; Martins, Flávia Letícia; Nogueira, Breno Valentim; Motta-Santos, Daisy; Araújo, Isabella Binotti; Forechi, Ludimila; Girardi, Adriana Castello Costa; Santos, Robson Augusto Souza; Mill, José Geraldo

    2015-01-01

    Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm. PMID:26495970

  19. Cardiac and renal effects of a transjugular intrahepatic portosystemic shunt in cirrhosis.

    PubMed

    Busk, Troels M; Bendtsen, Flemming; Møller, Søren

    2013-05-01

    Refractory ascites and recurrent variceal bleeding are among the serious complications of portal hypertension and cirrhosis for which a transjugular intrahepatic portosystemic shunt (TIPS) can be used. Cirrhotic patients have varying degrees of haemodynamic derangement, mainly characterized by peripheral arterial vasodilatation, central underfilling and activation of several vasoactive systems. These changes affect the heart, the lungs and the kidneys in particular. The cardiac effects of TIPS are immediate and are related to the redirection of blood from the splanchnic circulation into the systemic circulation, resulting in worsening of the hyperdynamic circulation with increasing cardiac output and decreasing systemic vascular resistance; further, TIPS may unmask a latent diastolic dysfunction of the heart. However, the renal effects of TIPS seem to be beneficial as renal function tends to improve in patients with the hepatorenal syndrome. The clinical and haemodynamic effects of TIPS have been studied intensively and will be reviewed in the present paper. Considerable knowledge on the effects of TIPS on the pathophysiology of cirrhosis has been gained, but studies on the central haemodynamic effects are warranted to refine the already applied treatments and develop new treatment modalities. PMID:23325273

  20. (1) H NMR metabolomics analysis of renal cell carcinoma cells: Effect of VHL inactivation on metabolism.

    PubMed

    Cuperlovic-Culf, Miroslava; Cormier, Kevin; Touaibia, Mohamed; Reyjal, Julie; Robichaud, Sarah; Belbraouet, Mehdi; Turcotte, Sandra

    2016-05-15

    Von Hippel-Lindau (VHL) is an onco-suppressor involved in oxygen and energy-dependent promotion of protein ubiquitination and proteosomal degradation. Loss of function mutations of VHL (VHL-cells) result in organ specific cancers with the best studied example in renal cell carcinomas. VHL has a well-established role in deactivation of hypoxia-inducible factor (HIF-1) and in regulation of PI3K/AKT/mTOR activity. Cell culture metabolomics analysis was utilized to determined effect of VHL and HIF-1α or HIF-2α on metabolism of renal cell carcinomas (RCC). RCC cells were stably transfected with VHL or shRNA designed to silence HIF-1α or HIF-2α genes. Obtained metabolic data was analysed qualitatively, searching for overall effects on metabolism as well as quantitatively, using methods developed in our group in order to determine specific metabolic changes. Analysis of the effect of VHL and HIF silencing on cellular metabolic footprints and fingerprints provided information about the metabolic pathways affected by VHL through HIF function as well as independently of HIF. Through correlation network analysis as well as statistical analysis of significant metabolic changes we have determined effects of VHL and HIF on energy production, amino acid metabolism, choline metabolism as well as cell regulation and signaling. VHL was shown to influence cellular metabolism through its effect on HIF proteins as well as by affecting activity of other factors. PMID:26620126

  1. Evolution.

    ERIC Educational Resources Information Center

    Mayr, Ernst

    1978-01-01

    Traces the history of evolution theory from Lamarck and Darwin to the present. Discusses natural selection in detail. Suggests that, besides biological evolution, there is also a cultural evolution which is more rapid than the former. (MA)

  2. [Cardiac effects of fenibut in development of experimental chronic renal insufficiency].

    PubMed

    Smirnov, A V; Barabanova, T A; Penchul, N A

    2003-01-01

    The effect of fenibut on the mechanical activity of myocardium was studied in vitro and in vivo in rats with experimental chronic renal insufficiency (CRI) in a regime of physiologically alternating load simulating the intact heart function. The administration of fenibut (10 mg/kg) in rats after nephrectomy prevents the development of myocardial hyperfunction (characteristic of the animals with CRI in stage 1). In in vitro experiments on isolated myocardium fenibut also decreased the myocardial hyperfunction and reduced contractility to a control level, which was accompanied by accelerated relaxation in all finite systolic lengths. PMID:14558346

  3. The effect of cyclosporin A on peripheral blood T cell subpopulations in renal allografts.

    PubMed Central

    Sweny, P; Tidman, N

    1982-01-01

    Treatment with cyclosporin A (CyA) produces a reversal of the normal ratio of OKT4+ (inducer type) to OKT84 (suppressor-cytotoxic type) cells so that renal allograft recipients on CyA alone develop a four-fold increase in the absolute number of circulating OKT8 positive cells. Conventional immunosuppression with azathioprine and prednisolone reduces both populations of T cells without altering the ratio of OKT4+ to OKT8+ cells. This effect of CyA may help to explain its action as an immunosuppressive agent. PMID:6210475

  4. Analgesic effect of ceruletide compared with pentazocine in biliary and renal colic: a prospective, controlled, double-blind study.

    PubMed

    Lishner, M; Lang, R; Jutrin, I; De-Paolis, C; Ravid, M

    1985-06-01

    The analgesic effect of ceruletide in biliary and renal colic was evaluated by a randomized, double-blind study in 82 patients. Ceruletide was compared with pentazocine, a well-established analgetic agent. Rapid and effective analgesia was obtained by intramuscular injection of ceruletide 0.5 micrograms/kg in 56 patients with biliary colic. The analgesic effect of ceruletide compared well with pentazocine 0.5 mg/kg im, and was associated with remarkably fewer side effects. In 26 patients with renal colic, ceruletide was significantly inferior to pentazocine. These data support the recommendation of ceruletide as a first-choice analgetic agent for biliary colic. PMID:3891284

  5. Effects of Yishen Pinggan Recipe on Renal Protection and NF-κB Signaling Pathway in Spontaneously Hypertensive Rats

    PubMed Central

    Luo, Guodong; Zhu, Xiying; Gao, Zhongxiang; Ge, Huaxun; Yu, Yang; Guo, Yuanyuan; Zheng, Jian-Pu; Liu, Longmin

    2016-01-01

    Inflammation is an important etiological factor of hypertensive renal damage. The effects of Yishen Pinggan Recipe (YPR) on urine microalbumin, histology, and NF-κB/P65, IκB-α, IL-1β, IL-6, and TNF-α in renal tissues were evaluated in SHR to explore the mechanism of its renal protection in hypertensive renal damage. The SBP of 12-week-old SHR was 192.41 ± 3.93 mmHg and DBP was 142.38 ± 5.79 mmHg. Without treatment, the 24-week-old SHRs' SBP was 196.96 ± 3.77 mmHg and DBP was 146.08 ± 4.82 mmHg. After the 12-week-old SHR were administered YPR for 12 weeks, the rats' SBP was 161.45 ± 7.57 mmHg and DBP was 117.21 ± 5.17 mmHg; YPR could lower blood pressure in SHR. And renal function damage was observed in 24-week-old SHR without treatment, manifested as urine protein and morphological changes which could be inhibited by YPR. In addition, YPR could reduce the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in kidneys. It could also inhibit the nuclear translocation of NF-κB p65 and degradation of IκB-α in renal cells, indicating that the NF-κB signaling pathway was inhibited by YPR. Finally, the study suggests that YPR could significantly improve the renal function in SHR. The mechanism could be attributed to its inhibition of renal NF-κB signaling pathway and inflammation. PMID:27069492

  6. Protective effect of lyophilized recombinant human brain natriuretic peptide on renal ischemia/reperfusion injury in mice.

    PubMed

    Cao, X; Xia, H Y; Zhang, T; Qi, L C; Zhang, B Y; Cui, R; Chen, X; Zhao, Y R; Li, X Q

    2015-01-01

    Brain natriuretic peptide (BNP) has a protective effect on acute injury of the heart, brain, and lung. However, its role in acute kidney injury (AKI) remains unclear. The aim of this study was to investigate the effect of lyophilized recombinant human BNP (lrh-BNP) on AKI and the underlying molecular mechanisms. An experimental model for AKI was established using an ischemia/reperfusion (I/R) procedure. Healthy adult BALB/c mice were randomized to the sham, I/R, and lrh-BNP-treated post-I/R (BNP + I/R) groups. Post-operatively, the BNP + I/R group was subcutaneously injected with lrh-BNP (0.03 μg·kg(-1)·min(-1)), whereas the other groups received saline at the same dose. Serum creatinine (Scr) and blood urea nitrogen levels were examined; tissue staining was performed to evaluate the degree of I/R injury (IRI). Ki67 positive staining of renal tubular epithelial cells was observed using immunofluorescence confocal laser scanning to assess the effect of BNP on cell proliferation after IRI. Inflammatory factor expression levels were detected to evaluate the effect of BNP on renal inflammation. Compared with the sham group, the I/R group showed increased Scr levels, severe tubular injury of the renal outer medulla, increased Kim-1 mRNA expression, an increased number of infiltrative macrophages in the renal interstitium, and increased TNF-α, IL- 1β, IL-6, MCP-1, and HIF-1α mRNA expression. BNP delivery significantly reduced all pathological changes in the I/R group. The protective role of BNP in murine renal IRI may be associated with its inhibition of renal interstitial inflammation and hypoxia and its promotion of renal tubule repair. PMID:26535643

  7. Diabetes-Induced Decrease in Renal Oxygen Tension: Effects of an Altered Metabolism

    NASA Astrophysics Data System (ADS)

    Palm, Fredrik; Carlsson, Per-Ola; Fasching, Angelica; Hansell, Peter; Liss, Per

    During conditions with experimental diabetes mellitus, it is evident that several alterations in renal oxygen metabolism occur, including increased mitochondrial respiration and increased lactate accumulation in the renal tissue. Consequently, these alterations will contribute to decrease the interstitial pO2, preferentially in the renal medulla of animals with sustained long-term hyperglycemia.

  8. Effects of anesthetics on the renal sympathetic response to anaphylactic hypotension in rats.

    PubMed

    Sun, Lingling; Tanida, Mamoru; Wang, Mofei; Kuda, Yuhichi; Kurata, Yasutaka; Shibamoto, Toshishige

    2014-01-01

    The autonomic nervous system plays an important role in rat anaphylactic hypotension. It is well known that sympathetic nerve activity and cardiovascular function are affected by anesthetics. However, the effects of different types of anesthesia on the efferent renal sympathetic nerve activity (RSNA) during anaphylactic hypotension remain unknown. Therefore, we determined the renal sympathetic responses to anaphylactic hypotension in anesthetized and conscious rats and the roles of baroreceptors in these responses. Sprague-Dawley rats were randomly allocated to anesthetic groups that were given pentobarbital, urethane, or ketamine-xylazine and to a conscious group. The rats were sensitized using subcutaneously injected ovalbumin. The systemic arterial pressure (SAP), RSNA and heart rate (HR) were measured. The effects of sinoaortic baroreceptor denervation on RSNA during anaphylaxis were determined in pentobarbital-anesthetized and conscious rats. In all of the sensitized rats, the RSNA increased and SAP decreased after antigen injection. At the early phase within 35 min of the antigen injection, the antigen-induced sympathoexcitation in the conscious rats was significantly greater than that in the anesthetized rats. Anaphylactic hypotension was attenuated in the conscious rats compared to the anesthetized rats. The anesthetic-induced suppression of SAP and RSNA was greater in the order ketamine-xylazine >urethane = pentobarbital. Indeed, in the rats treated with ketamine-xylazine, RSNA did not increase until 40 min, and SAP remained at low levels after the antigen injection. The baroreceptor reflex, as evaluated by increases in RSNA and HR in response to the decrease in SAP induced by sodium nitroprusside (SNP), was suppressed in the anesthetized rats compared with the conscious rats. Consistent with this finding, baroreceptor denervation attenuated the excitatory responses of RSNA to anaphylaxis in the conscious rats but not in the pentobarbital

  9. The effects of medicinal plants on renal function and blood pressure in diabetes mellitus.

    PubMed

    Musabayane, C T

    2012-09-01

    Diabetes mellitus is one of the most common chronic global diseases affecting children and adolescents in both the developed and developing nations. The major types of diabetes mellitus are type 1 and type 2, the former arising from inadequate production of insulin due to pancreatic β-cell dysfunction, and the latter from reduced sensitivity to insulin in the target tissues and/or inadequate insulin secretion. Sustained hyperglycaemia is a common result of uncontrolled diabetes and, over time, can damage the heart, eyes, kidneys and nerves, mainly through deteriorating blood vessels supplying the organs. Microvascular (retinopathy and nephropathy) and macrovascular (atherosclerotic) disorders are the leading causes of morbidity and mortality in diabetic patients. Therefore, emphasis on diabetes care and management is on optimal blood glucose control to avert these adverse outcomes. Studies have demonstrated that diabetic nephropathy is associated with increased cardiovascular mortality. In general, about one in three patients with diabetes develops end-stage renal disease (ESRD) which proceeds to diabetic nephropathy (DN), the principal cause of significant morbidity and mortality in diabetes. Hypertension, a well-established major risk factor for cardiovascular disease contributes to ESRD in diabetes. Clinical evidence suggests that there is no effective treatment for diabetic nephropathy and prevention of the progression of diabetic nephropathy. However, biomedical evidence indicates that some plant extracts have beneficial effects on certain processes associated with reduced renal function in diabetes mellitus. On the other hand, other plant extracts may be hazardous in diabetes, as reports indicate impairment of renal function. This article outlines therapeutic and pharmacological evidence supporting the potential of some medicinal plants to control or compensate for diabetes-associated complications, with particular emphasis on kidney function and

  10. Mitochondria-targeted peptide SS-31 attenuates renal injury via an antioxidant effect in diabetic nephropathy.

    PubMed

    Hou, Yanjuan; Li, Shuangcheng; Wu, Ming; Wei, Jinying; Ren, Yunzhuo; Du, Chunyang; Wu, Haijiang; Han, Caili; Duan, Huijun; Shi, Yonghong

    2016-03-15

    Oxidative stress is implicated in the pathogenesis of diabetic kidney injury. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge reactive oxygen species (ROS). Here, we investigated the effect and molecular mechanism of mitochondria-targeted antioxidant peptide SS-31 on injuries in diabetic kidneys and mouse mesangial cells (MMCs) exposed to high-glucose (HG) ambience. CD-1 mice underwent uninephrectomy and streptozotocin treatment prior to receiving daily intraperitoneal injection of SS-31 for 8 wk. The diabetic mice treated with SS-31 had alleviated proteinuria, urinary 8-hydroxy-2-deoxyguanosine level, glomerular hypertrophy, and accumulation of renal fibronectin and collagen IV. SS-31 attenuated renal cell apoptosis and expression of Bax and reversed the expression of Bcl-2 in diabetic mice kidneys. Furthermore, SS-31 inhibited expression of transforming-growth factor (TGF)-β1, Nox4, and thioredoxin-interacting protein (TXNIP), as well as activation of p38 MAPK and CREB and NADPH oxidase activity in diabetic kidneys. In vitro experiments using MMCs revealed that SS-31 inhibited HG-mediated ROS generation, apoptosis, expression of cleaved caspase-3, Bax/Bcl-2 ratio, and cytochrome c (cyt c) release from mitochondria. SS-31 normalized mitochondrial potential (ΔΨm) and ATP alterations, and inhibited the expression of TGF-β1, Nox4, and TXNIP, as well as activation of p38 MAPK and CREB and NADPH oxidase activity in MMCs under HG conditions. SS-31 treatment also could reverse the reduction of thioredoxin (TRX) biologic activity and upregulate expression of thioredoxin 2 (TRX2) in MMCs under HG conditions. In conclusion, this study demonstrates a protective effect of SS-31 against HG-induced renal injury via an antioxidant mechanism in diabetic nephropathy. PMID:26719366

  11. Effect of experimentally induced hepatic and renal failure on the pharmacokinetics of topiramate in rats.

    PubMed

    Matar, Kamal M; Tayem, Yasin I

    2014-01-01

    We aimed to investigate the effect of induced hepatic and renal failure on the pharmacokinetics of topiramate (TPM) in rats. Twenty-four Sprague-Dawley rats were used in this study. Renal or hepatic failure was induced by a single i.p. dose of 7.5 mg/kg cisplatin (n = 8) or 0.5 mL/kg carbon tetrachloride (CCl4) (n = 8), respectively. Three days after cisplatin dose or 24 h after CCl4 dose, the rats were administered a single oral dose of 20 mg/kg TPM. The plasma samples were quantified by LC-MS/MS method. Compared to control, plasma concentration-time profile in CCl4-treated and, to a lesser extent, in cisplatin-treated rats decreased more slowly particularly in the elimination phase. TPM oral clearance (CL/F) in CCl4-treated group was significantly lower than that in control (P < 0.001), whereas AUC0-∞, T1/2, and Vd/F were significantly higher in CCl4-treated rats compared to the control (P < 0.01). The CL/F was not significantly different between cisplatin-treated rats and control (P > 0.05). However, in cisplatin-treated rats, the T1/2 and Vd/F were significantly higher than that in the control group (P < 0.01). Both conditions failed to cause a significant effect on Cmax or Tmax. The present findings suggest that induced hepatic or renal failure could modify the pharmacokinetic profile of TPM in the rat. PMID:25009818

  12. Effect of Experimentally Induced Hepatic and Renal Failure on the Pharmacokinetics of Topiramate in Rats

    PubMed Central

    Matar, Kamal M.; Tayem, Yasin I.

    2014-01-01

    We aimed to investigate the effect of induced hepatic and renal failure on the pharmacokinetics of topiramate (TPM) in rats. Twenty-four Sprague-Dawley rats were used in this study. Renal or hepatic failure was induced by a single i.p. dose of 7.5 mg/kg cisplatin (n = 8) or 0.5 mL/kg carbon tetrachloride (CCl4) (n = 8), respectively. Three days after cisplatin dose or 24 h after CCl4 dose, the rats were administered a single oral dose of 20 mg/kg TPM. The plasma samples were quantified by LC-MS/MS method. Compared to control, plasma concentration-time profile in CCl4-treated and, to a lesser extent, in cisplatin-treated rats decreased more slowly particularly in the elimination phase. TPM oral clearance (CL/F) in CCl4-treated group was significantly lower than that in control (P < 0.001), whereas AUC0−∞, T1/2, and Vd/F were significantly higher in CCl4-treated rats compared to the control (P < 0.01). The CL/F was not significantly different between cisplatin-treated rats and control (P > 0.05). However, in cisplatin-treated rats, the T1/2 and Vd/F were significantly higher than that in the control group (P < 0.01). Both conditions failed to cause a significant effect on Cmax or Tmax. The present findings suggest that induced hepatic or renal failure could modify the pharmacokinetic profile of TPM in the rat. PMID:25009818

  13. Renal protein synthesis in diabetes mellitus: effects of insulin and insulin-like growth factor I

    SciTech Connect

    Barac-Nieto, M.; Lui, S.M.; Spitzer, A. )

    1991-06-01

    Is increased synthesis of proteins responsible for the hypertrophy of kidney cells in diabetes mellitus Does the lack of insulin, and/or the effect of insulin-like growth factor I (IGFI) on renal tubule protein synthesis play a role in diabetic renal hypertrophy To answer these questions, we determined the rates of 3H-valine incorporation into tubule proteins and the valine-tRNA specific activity, in the presence or absence of insulin and/or IGFI, in proximal tubule suspension isolated from kidneys of streptozotocin diabetic and control rats. The rate of protein synthesis increased, while the stimulatory effects of insulin and IGFI on tubule protein synthesis were reduced, early (96 hours) after induction of experimental diabetes. Thus, hypertrophy of the kidneys in experimental diabetes mellitus is associated with increases in protein synthesis, rather than with decreases in protein degradation. Factor(s) other than the lack of insulin, or the effects of IGFI, must be responsible for the high rate of protein synthesis present in the hypertrophying tubules of diabetic rats.

  14. Protective effects of tirofiban on ischemia/reperfusion-induced renal injury in vivo and in vitro.

    PubMed

    Guan, Weiwei; Wang, Zhen; Liu, Yukai; Han, Yu; Ren, Hongmei; Eric Wang, Wei; Yang, Jian; Zhou, Lin; Zeng, Chunyu

    2015-08-15

    Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is widely used in the management of patients with unstable angina or myocardial infarction, and shows protective effects on ischemia/reperfusion (I/R) injured heart. Whether or not it has protective effect on I/R injured kidney is not known. The present in vivo and in vitro study found that serum creatinine (SCR) and blood urea nitrogen (BUN) were significantly increased in I/R rats, accompanied by histopathological damage of the kidney. Apoptotic cells, leukocyte infiltration and ROS production were increased in I/R rats. Pretreatment by intravenous injection of tirofiban (200μg/kg) reduced SCR and BUN levels, ameliorated renal histopathological changes, and decreased ROS production, cell apoptosis and leukocyte infiltration in I/R injured kidney. Our further study showed that the protection of tirofiban might be associated with the restoration of eNOS/iNOS balance, since inhibition of NO production blocked the tirofiban-mediated renal protection on I/R injury. The present in vivo and in vitro study indicated that tirofiban pretreatment exerts a protective effect on I/R injury in kidney through regulation of eNOS/iNOS balance. PMID:25981297

  15. Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil

    PubMed Central

    Guerra, Augusto Afonso; Silva, Grazielle Dias; Andrade, Eli Iola Gurgel; Cherchiglia, Mariângela Leal; Costa, Juliana de Oliveira; Almeida, Alessandra Maciel; Acurcio, Francisco de Assis

    2015-01-01

    OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation. METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results. RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44. CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. However, regimens containing cyclosporine were more cost-effective. PMID:25741648

  16. 'Transcollateral' Renal Angioplasty for a Completely Occluded Renal Artery

    SciTech Connect

    Chandra, Subash; Chadha, Davinder S. Swamy, Ajay

    2011-02-15

    Percutaneous transluminal renal angioplasty with stenting has been effective in the control of hypertension, renal function, and pulmonary edema caused by atherosclerotic renal artery stenosis. However, the role of the procedure has not been fully established in the context of chronic total occlusion of renal artery. We report the successful use of this procedure in 57-year-old male patient who reported for evaluation of a recent episode of accelerated hypertension. A renal angiogram in this patient showed ostial stenosis of the right renal artery, which was filling by way of the collateral artery. Renal angioplasty for chronic total occlusion of right renal artery was successfully performed in a retrograde fashion through a collateral artery, thereby leading to improvement of renal function and blood pressure control.

  17. Mars mission effects on Space Station evolution

    NASA Technical Reports Server (NTRS)

    Askins, Barbara S.; Cook, Stephen G.

    1989-01-01

    The permanently manned Space Station scheduled to be operational in low earth by the mid 1990's, will provide accommodations for science, applications, technology, and commercial users, and will develop enabling capabilities for future missions. A major aspect of the baseline Space Station design is that provisions for evolution to greater capabilities are included in the systems and subsystems designs. User requirements are the basis for conceptual evolution modes or infrastructure to support the paths. Four such modes are discussed in support of a Human to Mars mission, along with some of the near term actions protecting the future of supporting Mars missions on the Space Station. The evolution modes include crew and payload transfer, storage, checkout, assembly, maintenance, repair, and fueling.

  18. The effect of hemodialysis, vitamin D metabolites and renal transplantation on the skeletal demineralization associated with renal osteodystrophy: a computerized histomorphometric analysis.

    PubMed

    Main, J; Velasco, N; Catto, G R; Fraser, R A; Edward, N; Adami, S; O'Riordan, J L

    1986-12-01

    Twenty-three patients with end-stage renal failure treated by hemodialysis or transplantation were followed for up to 10 years. Sequential full thickness iliac crest bone biopsies were obtained to assess the effects on bone disease of hemodialysis, treatment with 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] and renal transplantation. The biopsies were analyzed by a computerized histomorphometric technique which allowed accurate measurements of calcified bone and osteoid areas. Serum aluminum and parathyroid hormone concentrations were also monitored. Hemodialysis was associated with a loss of calcified bone and an increase in osteoid areas. The progressive bone loss was arrested but not reversed following treatment with either 1,25-(OH)2D3 or 24,25-(OH)2D3. Osteoid area was unchanged or reduced following treatment with 1,25-(OH)2D3 in all but three patients who had serum aluminum concentrations in excess of 5 mumol/l. 24,25-(OH)2D3 was not effective in reducing osteoid area, and combined treatment with 1,25 and 24,25-(OH)2D3 had no effect beyond that expected with 1,25-(OH)2D3 alone. Bone biopsies showed loss of calcified bone and an increase in osteoid areas one year and more after successful renal transplantation in five patients. Nineteen of the 23 patients developed serum aluminum concentrations greater than 3 mumol/l, probably because of the use of oral aluminum hydroxide as a phosphate binding agent. In these patients serum parathyroid hormone concentrations greater than 600 pg/ml appeared to prevent the development of osteopenia. PMID:3542321

  19. Immunopathologic effects of scorpion venom on hepato-renal tissues: Involvement of lipid derived inflammatory mediators.

    PubMed

    Lamraoui, Amal; Adi-Bessalem, Sonia; Laraba-Djebari, Fatima

    2015-10-01

    Scorpion venoms are known to cause different inflammatory disorders through complex mechanisms in various tissues. In the study here, the involvement of phospholipase A2 (PLA2) and cyclo-oxygenase (COX)-derived metabolites in hepatic and renal inflammation responses were examined. Mice were envenomed with Androctonus australis hector scorpion venom in the absence or presence of inhibitors that can interfere with lipid inflammatory mediator synthesis, i.e., dexamethasone (PLA2 inhibitor), indomethacin (non-selective COX-1/COX-2 inhibitor), or celecoxib (selective COX-2 inhibitor). The inflammatory response was assessed by evaluating vascular permeability changes, inflammatory cell infiltration, oxidative/nitrosative stress marker levels, and by histologic and functional analyses of the liver and kidney. Results revealed that the venom alone induced an inflammatory response in this tissues marked by increased microvascular permeability and inflammatory cell infiltration, increases in levels of nitric oxide and lipid peroxidation, and decreases in antioxidant defense. Moreover, significant alterations in the histological architecture of these organs were associated with increased serum levels of some metabolic enzymes, as well as urea and uric acid. Pre-treatment of mice with dexamethasone led to significant decreases of the inflammatory disorders in the hepatic parenchyma; celecoxib pre-treatment seemed to be more effective against renal inflammation. Indomethacin pre-treatment only slightly reduced the inflammatory disorders in the tissues. These results suggest that the induced inflammation response in liver was mediated mainly by PLA2 activation, while the renal inflammatory process was mediated by prostaglandin formation by COX-2. These findings provide additional insight toward the understanding of activated pathways and related mechanisms involved in scorpion envenoming syndrome. PMID:26231296

  20. Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats.

    PubMed

    Amaral, Liliany S de Brito; Silva, Fernanda A; Correia, Vicente B; Andrade, Clara Ef; Dutra, Bárbara A; Oliveira, Márcio V; Magalhães, Amélia Cm de; Volpini, Rildo A; Seguro, Antonio C; Coimbra, Terezila M; Soares, Telma de J

    2016-02-01

    This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney. PMID:26490345

  1. The effects of renal denervation on resistant hypertension patients: a meta-analysis.

    PubMed

    Zhang, Xiaojuan; Wu, Nie; Yan, Wenjuan; Zhou, Chunya; Guo, Hua

    2016-08-01

    We carried out this meta-analysis to assess the effects of renal denervation (RDN) on resistant hypertension patients. According to the collaborative review group search strategy, we searched MEDLINE (1996 to 2015.10); EBCO (1996 to 2015.10) and CNKI. A meta-analysis was carried out using RevMan 5.0. We identified 11 reports that fulfilled the inclusion criteria for our review. Controlled trials reporting systolic blood pressure (SBP), diastolic blood pressure in RDN, and control groups at the 6-month follow-up in patients with resistant hypertension were systematically reviewed. Pooled analysis of all 11 included studies showed significant reductions in SBP (weighted mean difference -13.9 mmHg, 95% confidence interval -21.17 to -6.63, P=0.00025, I=93%) and diastolic blood pressure (weighted mean difference -4.41 mmHg, 95% confidence interval -6.95 to -1.88, P=0.004, I=90%) compared with the control group at the 6-month follow-up. Six controlled trials reported specific values of ambulatory SBP that showed no significant difference between two groups. It has also been found that RDN has benefits in protecting cardiac and renal function compared with the control group without increasing adverse events. In conclusion, this meta-analysis shows that RDN is superior to the control group in lowering office blood pressure rather than ambulatory SBP, and might have other potential benefits to protect heart and renal function. PMID:26901340

  2. Effects of simulated heliox diving at high altitudes on blood cells, liver functions and renal functions.

    PubMed

    Hu, Hui-Jun; Fan, Dan-Feng; Lv, Yan; Zhang, Yu; Yang, Chen; Zhao, Ling; Zhao, Ru-Gang; Pan, Xiao-Wen

    2013-01-01

    The aim of the present study was to examine the effects of simulated heliox diving at high altitudes on divers' blood cells, liver functions and renal functions. In this experiment, four divers lived for nine consecutive days in a dual-function high-low pressure chamber, which simulated air pressure at an altitude of 3,000 meters and at a 30-meter depth; an altitude of 4,000 meters and 30-meter depth; and at an altitude of 5,200 meters and 30 meters and 50 meters in depth. Total time underwater was 60 minutes. The subjects breathed heliox (with oxygen at 40% and helium at 60%) during the simulated 30-meter dive from zero altitude to 30 meters and while remaining underwater; they breathed air while ascending from 30 meters to 18. They breathed heliox (with oxygen at 26.7% and helium at 73.3%) in the simulated dive from zero altitude to 50 meters underwater, in remaining underwater and in ascending from 50 meters to 29; air while ascending from 29 meters to 18. Pure oxygen was breathed while ascending from 18 meters to the surface; then air. Results indicated: (1) the correlating indices of routine blood, liver and renal functions, and urine routine were all within normal reference ranges; and (2) the indices tested at other periods of time were not significantly different (p > 0.05) from the results at zero-meter level and 3,000-meter level. The study suggests that the heliox diving processes at different high altitudes simulated in this experiment have no significant impact upon divers' blood routine, liver functions and renal functions. PMID:23957203

  3. The evolution and effectiveness of graduated licensing.

    PubMed

    Simpson, Herb M

    2003-01-01

    This paper traces the history of graduated licensing, starting about the point in time when Pat Waller's paper on the genesis of the concept ends, and examines the extent to which graduated licensing has produced reductions in collisions. It concludes with some general observations about future research needs, anticipating several of the papers that follow. The evolution of graduated licensing is chronicled, beginning with the early and largely unsuccessful efforts to introduce it in the United States in the late 1970s, through the pioneering efforts in New Zealand, which resulted in the first truly graduated system in 1987, to Canada where the program was introduced 7 years later, to the United States where it has flourished in more recent years. This 25-year history lesson hopefully creates an appreciation for the somewhat torturous journey that graduated licensing has experienced in achieving acceptance among the public and policy-makers-a journey that is not yet over, as subsequent papers in the symposium will show. The proliferation of graduated licensing in recent years is a mixed blessing-the wider adoption of graduated licensing has been a very positive development, but the programs that have evolved are anything but homogeneous in structure or content. Although this is often necessary for various reasons, it is worrisome that some programs are graduated licensing in name only. This suggests that future efforts to promote graduated licensing must emphasize adherence to the fundamental risk reduction and multistage principles on which the concept is based. The paper also considers the extent to which graduated licensing achieves its objective of reducing collisions among those covered by the program. Understandably, most jurisdictions would not introduce graduated licensing until it was shown to be effective and this, to some extent, slowed the process of implementation. The obvious irony is that it could not be shown to be effective until it was introduced

  4. Acute effect of high dose (48 mg) of piretanide in advanced renal insufficiency.

    PubMed Central

    Hadj Aissa, A; Pozet, N; Labeeuw, M; Pellet, M; Traeger, J

    1981-01-01

    1 The acute effects of a high dose of piretanide, a new potent diuretic were studied in eight patients with severely impaired renal function (GFR between 0.09 and 0.17 ml s-1 1.73 m-2). 2 After hydration and following two control periods, a single dose of 48 mg piretanide was ingested. Thereafter, urine was collected every 30 min for 2 h and every hour for the next 4 h. Urinary fluid losses were replaced orally (100 ml of water ever hour) and intravenously (isotonic saline + glucose infusion). 3 The following measurements were made: urine flow rate, clearances of inulin, PAH, urea, creatinine, uric acid, osmolar and free water clearances, excretion rates of sodium, chloride, potassium, calcium, phosphate, bicarbonate, ammonium, titratable acidity and urine pH. 4 Piretanide (48 mg) appeared to be effective in advanced renal insufficiency, producing a significant increase in urine flow rate, in sodium, chloride, potassium and calcium excretion and in Cosm. 5 There was no significant change in GFR, as measured by inulin clearance, or in the other measured parameters. PMID:7213511

  5. Effect of exercise on markers of vascular health in renal transplant recipients.

    PubMed

    Piťha, J; Králová Lesná, I; Stávek, P; Mahrová, A; Racek, J; Sekerková, A; Teplan, V; Štollová, M

    2015-01-01

    The cornerstone of cardiovascular risk management is lifestyle intervention including exercise which could exert favorable impact also in renal transplant recipients. Nevertheless, reliable assessment of the effect of lifestyle interventions is complicated and the available data in this population are not consistent. The aim of the study was to evaluate the effect of physical activity on selected laboratory markers of vascular health including circulating stem cells, endothelial progenitor cells, microparticles, and plasma asymmetric dimethyl arginine in renal transplant recipients. Nineteen men and 7 women were recruited in 6-month program of standardized and supervised exercise. Control group consisted of 23 men and 13 women of similar age and body mass index not included into the program. One year after the transplantation, the main difference between intervention and control group was found in the change of endothelial progenitor cells (p=0.006). Surprisingly, more favorable change was seen in the control group in which endothelial progenitor cells significantly increased compared to the intervention group. The explanation of this finding might be a chronic activation of reparative mechanisms of vascular system in the population exposed to multiple risk factors which is expressed as relatively increased number of endothelial progenitor cells. Therefore, their decrease induced by exercise might reflect stabilization of these processes. PMID:26447524

  6. Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Transplant Patients Converted to Sirolimus.

    PubMed

    Mandelbrot, D A; Alberú, J; Barama, A; Marder, B A; Silva, H T; Flechner, S M; Flynn, A; Healy, C; Li, H; Tortorici, M A; Schulman, S L

    2015-12-01

    This prospective, randomized, double-blind, placebo-controlled study evaluated the effects of ramipril on urinary protein excretion in renal transplant patients treated with sirolimus following conversion from a calcineurin inhibitor. Patients received ramipril or placebo for up to 6 weeks before conversion and 52 weeks thereafter. Doses were increased if patients developed proteinuria (urinary protein/creatinine ratio ≥0.5); losartan was given as rescue therapy for persistent proteinuria. The primary end point was time to losartan initiation. Of 295 patients randomized, 264 met the criteria for sirolimus conversion (ramipril, 138; placebo, 126). At 52 weeks, the cumulative rate of losartan initiation was significantly lower with ramipril (6.2%) versus placebo (23.2%) (p < 0.001). No significant differences were observed between ramipril and placebo for change in glomerular filtration rate from baseline (p = 0.148) or in the number of patients with biopsy-confirmed acute rejection (13 vs. 5, respectively; p = 0.073). One patient in the placebo group died due to cerebrovascular accident. Treatment-emergent adverse events were consistent with the known safety profile of sirolimus and were not potentiated by ramipril co-administration. Ramipril was effective in reducing the incidence of proteinuria for up to 1 year following conversion to sirolimus in maintenance renal transplant patients. PMID:26176342

  7. Glypican-3 modulates BMP- and FGF-mediated effects during renal branching morphogenesis.

    PubMed

    Grisaru, S; Cano-Gauci, D; Tee, J; Filmus, J; Rosenblum, N D

    2001-03-01

    The kidney of the Gpc3-/ mouse, a novel model of human renal dysplasia, is characterized by selective degeneration of medullary collecting ducts preceded by enhanced cell proliferation and overgrowth during branching morphogenesis. Here, we identify cellular and molecular mechanisms underlying this renal dysplasia. Glypican-3 (GPC3) deficiency was associated with abnormal and contrasting rates of proliferation and apoptosis in cortical (CCD) and medullary collecting duct (MCD) cells. In CCD, cell proliferation was increased threefold. In MCD, apoptosis was increased 16-fold. Expression of Gpc3 mRNA in ureteric bud and collecting duct cells suggested that GPC3 can exert direct effects in these cells. Indeed, GPC3 deficiency abrogated the inhibitory activity of BMP2 on branch formation in embryonic kidney explants, converted BMP7-dependent inhibition to stimulation, and enhanced the stimulatory effects of KGF. Similar comparative differences were found in collecting duct cell lines derived from GPC3-deficient and wild type mice and induced to form tubular progenitors in vitro, suggesting that GPC3 directly controls collecting duct cell responses. We propose that GPC3 modulates the actions of stimulatory and inhibitory growth factors during branching morphogenesis. PMID:11180950

  8. Renal Artery Embolization

    PubMed Central

    Sauk, Steven; Zuckerman, Darryl A.

    2011-01-01

    Renal artery embolization (RAE) is an effective minimally invasive alternative procedure for the treatment of a variety of conditions. Since the 1970s when RAE was first developed, technical advances and growing experience have expanded the indications to not only include treatment of conditions such as symptomatic hematuria and palliation for metastatic renal cancer, but also preoperative infarction of renal tumors, treatment of angiomyolipomas, vascular malformations, medical renal disease, and complications following renal transplantation. With the drastically improved morbidity associated with this technique in part due to the introduction of more precise embolic agents and smaller delivery catheters, RAE continues to gain popularity for various urologic conditions. The indications and techniques for renal artery embolization are reviewed in the following sections. PMID:23204638

  9. The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease.

    PubMed

    Zatelli, A; Roura, X; D'Ippolito, P; Berlanda, M; Zini, E

    2016-01-01

    Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD); renal diets and angiotensin-converting enzyme (ACE)-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4) were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22) received enalapril (0.5 mg/kg, q12h) and in group B (n=22) benazepril (0.5 mg/kg, q24h); in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS), serum concentrations of creatinine, blood urea nitrogen (BUN), albumin and total proteins, and urine protein-to-creatinine (UPC) ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001). Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05). In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet. PMID:27540513

  10. The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease

    PubMed Central

    Zatelli, A.; Roura, X.; D’Ippolito, P.; Berlanda, M.; Zini, E.

    2016-01-01

    Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD); renal diets and angiotensin-converting enzyme (ACE)-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4) were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22) received enalapril (0.5 mg/kg, q12h) and in group B (n=22) benazepril (0.5 mg/kg, q24h); in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS), serum concentrations of creatinine, blood urea nitrogen (BUN), albumin and total proteins, and urine protein-to-creatinine (UPC) ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001). Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05). In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet. PMID:27540513

  11. Non-Renal Effects and the Risk Assessment of Environmental Cadmium Exposure

    PubMed Central

    Barregard, Lars; Bergdahl, Ingvar A.; Nordberg, Gunnar F.; Nordberg, Monica; Skerfving, Staffan

    2014-01-01

    Background: Exposure to cadmium (Cd) has long been recognized as a health hazard, both in industry and in general populations with high exposure. Under the currently prevailing health risk assessment, the relationship between urinary Cd (U-Cd) concentrations and tubular proteinuria is used. However, doubts have recently been raised regarding the justification of basing the risk assessment on this relationship at very low exposure. Objectives: Our objective was to review available information on health effects of Cd exposure with respect to human health risk assessment. Discussion: The associations between U-Cd and urinary proteins at very low exposure may not be due to Cd toxicity, and the clinical significance of slight proteinuria may also be limited. More importantly, other effects have been reported at very low Cd exposure. There is reason to challenge the basis of the existing health risk assessment for Cd. Our review of the literature found that exposure to low concentrations of Cd is associated with effects on bone, including increased risk of osteoporosis and fractures, and that this observation has implications for the health risk assessment of Cd. Other effects associated with Cd should also be considered, in particular cancer, although the information is still too limited for appropriate use in quantitative risk assessment. Conclusion: Non-renal effects should be considered critical effects in the health risk assessment of Cd. Citation: Åkesson A, Barregard L, Bergdahl IA, Nordberg GF, Nordberg M, Skerfving S. 2014. Non-renal effects and the risk assessment of environmental cadmium exposure. Environ Health Perspect 122:431–438; http://dx.doi.org/10.1289/ehp.1307110 PMID:24569905

  12. Renal Calculi

    PubMed Central

    Yendt, E. R.

    1970-01-01

    The pathogenesis of renal calculi is reviewed in general terms followed by the results of investigation of 439 patients with renal calculi studied by the author at Toronto General Hospital over a 13-year period. Abnormalities of probable pathogenetic significance were encountered in 76% of patients. Idiopathic hypercalciuria was encountered in 42% of patients, primary hyperparathyroidism in 11%, urinary infection in 8% and miscellaneous disorders in 8%. The incidence of uric acid stones and cystinuria was 5% and 2% respectively. In the remaining 24% of patients in whom no definite abnormalities were encountered the mean urinary magnesium excretion was less than normal. Of 180 patients with idiopathic hypercalciuria, only 24 were females. In the diagnosis of hyperparathyroidism, the importance of detecting minimal degrees of hypercalcemia is stressed; attention is also drawn to the new observation that the upper limit of normal for serum calcium is slightly lower in females than in males. The efficacy of various measures advocated for the prevention of renal calculi is also reviewed. In the author's experience the administration of thiazides has been particularly effective in the prevention of calcium stones. Thiazides cause a sustained reduction in urinary calcium excretion and increase in urinary magnesium excretion. These agents also appear to affect the skeleton by diminishing bone resorption and slowing down bone turnover. PMID:5438766

  13. Azolimine: a nonsteroidal antagonist of the effects of mineralocorticoids on renal electrolyte excretion.

    PubMed

    Gussin, R Z; Ronsberg, M A; Stokey, E H; Cummings, J R

    1975-10-01

    Azolimine, CL 90,748, an imidazolidinone, displayed the capacity to antagonize the effects of mineralocorticoids on renal electrolyte excretion in several animal models. Although large doses of azolimine produced natriuresis in adrenalectomized rats in the absence of exogenous mineralocorticoid, its effectiveness was greater in the presence of a steroid agonist. However, in conscious dogs given an infusion of saline plus dextrose, azolimine was only effective when desoxycorticosterone (DCA) was administered. The drug, therefore, may not be a pure competitive antagonist of mineralocorticoid, but its greater efficacy in the presence of mineralocorticoid distinguishes it from noncompetitive mineralocorticoid antagonists as amiloride and triamterene. Azolimine significantly improved the urinary Na/K ratio when used in combination with thiazides, furosemide and other classical diuretics both in adrenalectomized, desoxycorticosterone-treated rats and in sodium-deficient rats. PMID:1181406

  14. Protective Effect of Aqueous Crude Extract of Neem (Azadirachta indica) Leaves on Plasmodium berghei-Induced Renal Damage in Mice

    PubMed Central

    Somsak, Voravuth; Chachiyo, Sukanya; Jaihan, Ubonwan; Nakinchat, Somrudee

    2015-01-01

    Malaria is a major public health problem in the world because it can cause of death in patients. Malaria-associated renal injury is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. Therefore, new plant extracts to protect against renal injury induced by malaria infection are urgently needed. In this study, we investigated the protective effect of aqueous crude extract of Azadirachta indica (neem) leaves on renal injury induced by Plasmodium berghei ANKA infection in mice. ICR mice were injected intraperitoneally with 1 × 107 parasitized erythrocytes of PbANKA, and neem extracts (500, 1,000, and 2,000 mg/kg) were given orally for 4 consecutive days. Plasma blood urea nitrogen (BUN) and creatinine levels were subsequently measured. Malaria-induced renal injury was evidenced as marked increases of BUN and creatinine levels. However, the oral administration of neem leaf extract to PbANKA infected mice for 4 days brought back BUN and creatinine levels to near normalcy, and the highest activity was observed at doses of 1,000 and 2,000 mg/kg. Additionally, no toxic effects were found in normal mice treated with this extract. Hence, neem leaf extract can be considered a potential candidate for protection against renal injury induced by malaria. PMID:26379714

  15. The pharmacokinetics and diuretic effects of piretanide in chronic renal insufficiency.

    PubMed Central

    Berg, K J; Walstad, R A; Bergh, K

    1983-01-01

    The pharmacokinetics of piretanide, a new loop diuretic, were studied in four patients with GFR 4.7-14.8 ml/min. An oral dose of piretanide 18 mg was given at 08.00 h in two patients and at 08.00 h and 14.00 h in two. Blood samples were drawn after 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. Serum concentrations of piretanide were estimated by radioimmunoassay. The peak serum concentration of piretanide (1-2 h after drug administration) was 510-880 ng/ml, independent of renal function. Elimination half life (t1/2) was 1.2-4.1 h, area under the curves (AUC(0,24)) 1.63-2.44 micrograms ml-1 h, volume of distribution (Vz) 0.30--0.741#kg, total plasma clearance (CL) 122.8-184.0 ml/min and renal clearance (CLR) 1.5-5.2 ml/min. The clinical effects of oral treatment with piretanide 18 mg twice daily were compared with bumetanide 3 mg twice daily in eight patients with renal failure (GFR 2.2-24.5 ml/min). Both drugs equally increased the 24 h output of urine (delta V), sodium (delta UNaV), chloride (delta UC1V), potassium (delta UKV) and calcium (delta UCaV). Fractional excretion of sodium (ENa%) was doubled by piretanide in patients with GFR less than 8 ml/min while a five fold increase was found in patients with GFR greater than 8 ml/min. The onset of effect was the same for both drugs, but the duration exceeded 6 h only for piretanide. Both drugs were most effective on the first of two consecutive treatment days. Delta UC1V was always greater than delta UNaV and urinary phosphate excretion was unchanged, as expected of a loop diuretic without significant proximal effects. Metabolic or clinical side effects were not noticed. PMID:6342640

  16. Human inorganic mercury exposure, renal effects and possible pathways in Wanshan mercury mining area, China.

    PubMed

    Li, Ping; Du, Buyun; Chan, Hing Man; Feng, Xinbin

    2015-07-01

    Rice can accumulate methylmercury (MeHg) and rice consumption is the main route of MeHg exposure for the local population in Guizhou, China. However, inorganic Hg (IHg) load in human body is not comprehensively studied in highly Hg polluted areas such as Hg mining areas. This study is designed to evaluate human IHg exposure, related renal effects and possible pathways in Wanshan Hg mining area, Guizhou, Southwest China. Residents lived within 3 km to the mine waste heaps showed high Urine Hg (UHg) concentrations and the geometrical means (Geomean) of UHg were 8.29, 5.13, and 10.3 μg/g Creatinine (Cr) at site A, D, and E, respectively. It demonstrated a gradient of UHg concentrations with the distance from the pollution sources. A significantly positive correlation between paired results for UHg concentrations and serum creatinine (SCr) was observed in this study, but not for UHg and blood urea nitrogen (BUN). There are significant increases of SCr in two quartiles with high UHg concentrations. The results indicated that human IHg exposure may cause impairment of renal function. By calculation of Probable Daily Intake from different routes, we found that dietary intake is the main pathway of IHg exposure for the local population, rather than inhalation of Hg vapor. PMID:25863593

  17. [Effects of cytokines on somatostatin in nude mice bearing human renal cell carcinoma].

    PubMed

    Li, G; Cao, G; Huo, J

    1997-06-01

    We studied the relationship between the production of SS and treatment with cytokines and a new method for the treatment of renal cell carcinoma. 4.4 x 10(6)RCC94616 cells were injected subcutaneously into the back of nude mice. Five groups with TNF, IL-2, rIFN, TNF + IL-2, TNF + rIFN and controls were randomly divided according to the mean diameter of experimental tumor. After the last injection of cytokines, 0.5-0.8 ml blood, 1g tumor tissue, para-tissue and normal tissue were havested respectively. Contents of SS were tested by radioimmunoassay. In the treatment groups with cytokines, the concentration of SS was changed, siginificantly increased in the TNF + IL-2 group (P < 0.01). The effect on distribution of SS by cytokines may also be mediated by the regulation of human immunity and antitumor activity. It may be suggested that the method of TNF + IL-2 + SS is best to treat renal cell carcinoma. PMID:10374465

  18. Effect of epsilon toxin-GFP on MDCK cells and renal tubules in vivo.

    PubMed

    Soler-Jover, Alex; Blasi, Juan; Gómez de Aranda, Inma; Navarro, Piedad; Gibert, Maryse; Popoff, Michel R; Martín-Satué, Mireia

    2004-07-01

    Epsilon toxin (epsilon-toxin), produced by Clostridium perfringens types B and D, causes fatal enterotoxemia, also known as pulpy kidney disease, in livestock. Recombinant epsilon-toxin-green fluorescence protein (epsilon-toxin-GFP) and epsilon-prototoxin-GFP were successfully expressed in Escherichia coli. MTT assays on MDCK cells confirmed that recombinant epsilon-toxin-GFP retained the cytotoxicity of the native toxin. Direct fluorescence analysis of MDCK cells revealed a homogeneous peripheral pattern that was temperature sensitive and susceptible to detergent. epsilon-Toxin-GFP and epsilon-prototoxin-GFP bound to endothelia in various organs of injected mice, especially the brain. However, fluorescence mainly accumulated in kidneys. Mice injected with epsilon-toxin-GFP showed severe kidney alterations, including hemorrhagic medullae and selective degeneration of distal tubules. Moreover, experiments on kidney cryoslices demonstrated specific binding to distal tubule cells of a range of species. We demonstrate with new recombinant fluorescence tools that epsilon-toxin binds in vivo to endothelial cells and renal tubules, where it has a strong cytotoxic effect. Our binding experiments indicate that an epsilon-toxin receptor is expressed on renal distal tubules of mammalian species, including human. PMID:15208360

  19. Renal accumulation and effects of intraperitoneal injection of extracted microcystins in omnivorous crucian carp (Carassius auratus).

    PubMed

    Li, Li; Xie, Ping; Lei, Hehua; Zhang, Xuezhen

    2013-08-01

    An acute toxicological experiment was designed to characterize the sequence of renal ultrastructural changes with accumulated MCs in crucian carp injected intraperitoneally (i.p.) with extracted microcystins (mainly MC-RR and -LR) at two doses, 50 and 200 μg MC-LReq. kg⁻¹ body weight. Quantitative and qualitative determinations of MCs in the kidney were conducted by HPLC and LC-MS, respectively. MC-RR content in kidney of crucian carp showed a time dose-dependent increase within 48 h post-injection, followed by a sharp decline afterward, while no MC-LR in kidney was detectable throughout the experiment. Ultrastructural changes in the kidney of crucian carp progressed with increasing accumulated MCs and exposure times within 48 h post-injection, whereas renal ultrastructural recovery of crucian carp in the 50 μg MC-LReq. kg⁻¹ dose group was evident at 168 h post-injection. Our ultrastructural observation suggests that the membranous structure is the main action site of MCs in the kidney, among which mitochondria damage in the tubules is clearly an early, and presumably a critically important effect of MCs. The increases in blood urea nitrogen (BUN) and creatinine (CR) in both dose groups further revealed severe impairment occurred in the kidney of crucian carp. PMID:23608020

  20. Chronic effects of lead on renin and renal sodium excretion. [Rats

    SciTech Connect

    Fleischer, N.; Mouw, D.R.; Vander, A.J.

    1980-05-01

    Rats were chronically give 0.5 mg/ml Pb in drinking water. This produced blood and renal lead concentratoins of approximately 30 )g/dl and 20)g/gm, respectively, significant kidney swelling, but no change in body weight or hematocrit. After 6 weeks of Pb treatment and during ingestion of a sodium-free diet, plasma, renin activity (PRA) was elevated (controls: same diet, no lead), but there was no change in plasma resin substrate (PRS). After 5 months the PRA was significantly higher in the lead-treated group even on a 1% NaCl diet, but the difference between groups disappeared on an Na-free diet; that is, the renin response to sodium deprivation was blunted. As early as 6 weeks after beginning lead treatment, the treated group manifested reduced ability to decrease Na excretion following removal of NaCl from the diet; steady-state sodium excretion was normal on either the 1% NaCl or Na-free diet. We conclude that changes in the renin angiotensin system and renal sodium handling may be important toxic effects of low doses of lead on the kidneys of rats.

  1. Effects of Diaceto-Dipropyl-Disulphide on Plasma Sialic Acid and Renal Tissue Thiol Levels in Alloxan Diabetic Rats

    PubMed Central

    Vickram; Thirumalarao, Kashinath Rattihalli; Raiker, Veena Gajana; Puttaswamy, Sandhya Hanumanthappa

    2016-01-01

    Introduction Plasma sialic acid levels are elevated in Diabetes Mellitus (DM) patients with proteinuria. Renal damage is mainly caused by free radicals that are excessively generated in DM. Thiols play an important role in the cellular antioxidative defence mechanisms mainly through thiol-disulphide exchange reaction. Diallyl disulphide, a garlic oil principle component, is known for its anti-diabetic properties. Its structural analogue, Diaceto-Dipropyl Disulphide (DADPDS), is a less toxic and more palatable disulphide and possesses similar anti-diabetic actions. Aim This study was undertaken to assess the usefulness of DADPDS in prevention of de-sialation of Glomerular Basement Membrane (GBM) in alloxan diabetic rats and to assess effect of DADPDS on renal tissue thiol levels. Materials and Methods Rats were divided into Normal, Diabetic and DADPDS treated diabetic groups. Diabetes was induced by intraperitoneal injection (IP) of alloxan. DADPDS was fed by gastric intubation. Plasma Sialic acid was determined by Ehrlich’s method and renal tissue thiol levels by Nitroprusside reaction method. Results This study showed a significant decrease (p<0.001) in plasma sialic acid, plasma glucose and renal tissue TBARS levels along with significant increase (p<0.001) in renal tissue thiol levels in DADPDS treated alloxan diabetic rats when compared to diabetic control rats. Conclusion Hence it may be concluded that DADPDS helps in preventing de-sialation of GBM in alloxan diabetic rats and improves renal tissue antioxidant defence mechanisms, may be through thiol-disulphide exchange reaction and thereby exhibits a possible clinical use in prevention of renal complications like diabetic nephropathy. PMID:27504279

  2. Brittleness Effect on Rock Fatigue Damage Evolution

    NASA Astrophysics Data System (ADS)

    Nejati, Hamid Reza; Ghazvinian, Abdolhadi

    2014-09-01

    The damage evolution mechanism of rocks is one of the most important aspects in studying of rock fatigue behavior. Fatigue damage evolution of three rock types (onyx marble, sandstone and soft limestone) with different brittleness were considered in the present study. Intensive experimental tests were conducted on the chosen rock samples and acoustic emission (AE) sensors were used in some of them to monitor the fracturing process. Experimental tests indicated that brittleness strongly influences damage evolution of rocks in the course of static and dynamic loading. AE monitoring revealed that micro-crack density induced by the applied loads during different stages of the failure processes increases as rock brittleness increases. Also, results of fatigue tests on the three rock types indicated that the rock with the most induced micro-cracks during loading cycles has the least fatigue life. Furthermore, the condition of failure surfaces of the studied rocks samples, subjected to dynamic and static loading, were evaluated and it was concluded that the roughness of failure surfaces is influenced by loading types and rock brittleness. Dynamic failure surfaces were rougher than static ones and low brittle rock demonstrate a smoother failure surface compared to high brittle rock.

  3. Cost-Effectiveness Analysis of the Spanish Renal Replacement Therapy Program

    PubMed Central

    Villa, Guillermo; Fernández–Ortiz, Lucía; Cuervo, Jesús; Rebollo, Pablo; Selgas, Rafael; González, Teresa; Arrieta, Javier

    2012-01-01

    ♦ Background: We undertook a cost-effectiveness analysis of the Spanish Renal Replacement Therapy (RRT) program for end-stage renal disease patients from a societal perspective. The current Spanish situation was compared with several hypothetical scenarios. ♦ Methods: A Markov chain model was used as a foundation for simulations of the Spanish RRT program in three temporal horizons (5, 10, and 15 years). The current situation (scenario 1) was compared with three different scenarios: increased proportion of overall scheduled (planned) incident patients (scenario 2); constant proportion of overall scheduled incident patients, but increased proportion of scheduled incident patients on peritoneal dialysis (PD), resulting in a lower proportion of scheduled incident patients on hemodialysis (HD) (scenario 3); and increased overall proportion of scheduled incident patients together with increased scheduled incidence of patients on PD (scenario 4). ♦ Results: The incremental cost-effectiveness ratios (ICERs) of scenarios 2, 3, and 4, when compared with scenario 1, were estimated to be, respectively, –€83 150, –€354 977, and –€235 886 per incremental quality-adjusted life year (ΔQALY), evidencing both moderate cost savings and slight effectiveness gains. The net health benefits that would accrue to society were estimated to be, respectively, 0.0045, 0.0211, and 0.0219 ΔQALYs considering a willingness-to-pay threshold of €35 000/ΔQALY. ♦ Conclusions: Scenario 1, the current Spanish situation, was dominated by all the proposed scenarios. Interestingly, scenarios 3 and 4 showed the best results in terms of cost-effectiveness. From a cost-effectiveness perspective, an increase in the overall scheduled incidence of RRT, and particularly that of PD, should be promoted. PMID:21965620

  4. Effects of cadmium on the renal and skeletal muscle microcirculation in rats

    SciTech Connect

    Zhang Chong.

    1990-01-01

    The effects of cadmium on the arteriolar diameters of the kidney and skeletal muscle were quantified, because of the hypertensive effect of cacmium. The effect of cacmium on the constrictor response of the renal arterioles to angiotensin II (Ang II) were also assessed. In vivo preparations of the rat hydronephrotic kidney and cremaster muscle were used for direct visualization of the microvessels with intravital television microscopy. Hydronephrosis was induced in twenty-seven male Wistar-Kyoto rats (150-180 g) by unilateral ureter ligation. The hydronephrotic kidney, with intact cortical circulation and innervation, was exteriorized in a specially designed bath for microcirculation observation 6-8 weeks following the ureter ligation. The cremaster muscle experiments were conducted in another thirty-seven male WKY rats (120-180 g). Disparate effects of cadmium were observed in these two microcirculation beds. Topical cadmium (1.35 [mu]M-0.45 mM) increased the diameters of the pre- and postglomerular vessels in the hydronephrotic kidney maximally by 15-26%. Cadmium (0.27 mM) inhibited the Ang II response of the arterioles non-competitively. However, intraperitoneally injected cadmium (2 mg/kg), which significantly increased the mean arterial pressure, did not dilate the arterioles nor alter the Ang II response. On the other hand, cadmium (13.5 [mu]M-0.72 mM) constricted the larger arterioles in the cremaster muscle (60-160 [mu]m) concentration-dependently, but not small arterioles (15-30 [mu]m). In summary, topical cadmium dilates renal arterioles and decreases their reactivity to Ang II, but constricts the larger cremaster arterioles. The disparate effects of cadmium suggest different Ca[sup 2+] utilization mechanisms in different vascular beds. The construction of the cremaster arterioles may contribute to cadmium-induced hypertension by increasing peripheral resistance.

  5. Comparative effects of chelating agents on distribution, excretion, and renal toxicity of inorganic mercury in rats

    SciTech Connect

    Kojima, S.; Shimada, H.; Kiyozumi, M. )

    1989-06-01

    The effects of three chelating agents, sodium N-benzyl-D-glucamine dithiocarbamate(NBG-DTC), 2,3-dimercaptopropanol(BAL), and D-penicillamine(D-PEN), on the distribution, excretion, and renal toxicity of inorganic mercury were compared in rats exposed to HgCl2. Rats were injected i.p. with 203HgCl2 (300 micrograms of Hg and 2 microCi of 203Hg/kg) and 30 min or 24 h later they were injected with a chelating agent (a quarter of an LD50). The injection of the chelating agents significantly enhanced the biliary and urinary excretions of mercury. BAL was the most effective for removal of mercury from the body at 30 min after mercury treatment. The extent of enhancing effect of the chelating agents for removal of mercury at 24 h after mercury was in the order NBG-DTC = BAL greater than D-PEN. The injection of BAL at 24 h after mercury treatment caused the redistribution of mercury to the heart and lung. NBG-DTC did not result in the redistribution of mercury to the heart, lung, and brain. Urinary excretion of protein and AST significantly increased 24-48 h after mercury treatment and decreased to the control values 72 h after mercury. The injection of the chelating agents at 30 min after mercury treatment significantly decreased the urinary excretion of protein and AST. In rats pretreated with mercury 24 h earlier, the chelating agents significantly decreased the urinary protein at 48 h after mercury treatment, but did not decrease the urinary AST. The results of this study indicate that the chelating agents are effective in removing mercury from the body, resulting in the protective effect against the mercury-induced renal damage.

  6. Renal and cardiovascular effects of caffeine: a dose-response study.

    PubMed

    Passmore, A P; Kondowe, G B; Johnston, G D

    1987-06-01

    The effects of increasing oral doses of caffeine (45, 90, 180 and 360 mg) on effective renal plasma flow (ERPF), plasma renin activity (PRA), serum electrolytes, plasma noradrenaline, blood pressure and heart rate were studied in eight healthy male volunteers. Urine volume was increased by 360 mg of caffeine only. At caffeine doses greater than 90 mg urinary sodium excretion was significantly increased. There were no changes in ERPF. Serum potassium was significantly reduced by 360 mg of caffeine. Caffeine increased systolic pressure in a dose related manner. Diastolic pressure was also increased, but not in relation to dose. A 360 mg dose of caffeine produced a late increase in heart rate. These changes were not associated with any alterations in PRA or in plasma noradrenaline. PMID:3297472

  7. Carbon tetrachloride-induced hepatic and renal damages in rat: inhibitory effects of cacao polyphenol.

    PubMed

    Suzuki, Koichiro; Nakagawa, Kiyotaka; Yamamoto, Takayuki; Miyazawa, Taiki; Kimura, Fumiko; Kamei, Masanori; Miyazawa, Teruo

    2015-01-01

    Here, we investigated the protective effect of cacao polyphenol extract (CPE) on carbon tetrachloride (CCl4)-induced hepato-renal oxidative stress in rats. Rats were administered CPE for 7 days and then received intraperitoneal injection of CCl4. Two hours after injection, we found that CCl4 treatment significantly increased biochemical injury markers, lipid peroxides (phosphatidylcholine hydroperoxide (PCOOH) and malondialdehyde (MDA)) and decreased glutathione peroxidase activity in kidney rather than liver, suggesting that kidney is more vulnerable to oxidative stress under the present experimental conditions. CPE supplementation significantly reduced these changes, indicating that this compound has antioxidant properties against CCl4-induced oxidative stress. An inhibitory effect of CPE on CCl4-induced CYP2E1 mRNA degradation may provide an explanation for CPE antioxidant property. Together, these results provide quantitative evidence of the in vivo antioxidant properties of CPE, especially in terms of PCOOH and MDA levels in the kidneys of CCl4-treated rats. PMID:25996516

  8. Cerebroprotective effects of RAS inhibitors: Beyond their cardio-renal actions.

    PubMed

    Kalra, Jaspreet; Prakash, Atish; Kumar, Puneet; Majeed, Abu Bakar Abdul

    2015-09-01

    Work on the brain renin-angiotensin system has been explored by various researchers and has led to elucidation of its basic physiologies and behavior, including its role in reabsorption and uptake of body fluid, blood pressure maintenance with angiotensin II being its prominent effector. Currently, this system has been implicated for its newly established effects, which are far beyond its cardio-renal effects accounting for maintenance of cerebral blood flow and cerebroprotection, seizure, in the etiology of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and bipolar disorder. In this review, we have discussed the distribution of angiotensin receptor subtypes in the central nervous system (CNS) together with enzymatic pathways leading to active angiotensin ligands and its interaction with angiotensin receptor 2 (AT2) and Mas receptors. Secondly, the use of angiotensin analogues (angiotensin converting enzyme inhibitors and AT1 and/or AT2 receptor blockers) in the treatment and management of the CNS disorders mentioned above has been discussed. PMID:25944853

  9. The Protective Effect of Remote Renal Preconditioning Against Hippocampal Ischemia Reperfusion Injury: Role of KATP Channels.

    PubMed

    Mehrjerdi, Fatemeh Zare; Aboutaleb, Nahid; Pazoki-Toroudi, Hamidreza; Soleimani, Mansoureh; Ajami, Marjan; Khaksari, Mehdi; Safari, Fatemeh; Habibey, Rouhollah

    2015-12-01

    Remote ischemic preconditioning (RIPC), which consists of several brief ischemia/reperfusion applied at the remote site of lethal ischemia reperfusion, can, through activating different mechanisms, increase the ability of the body's endogenous protection against prolonged ischemia/reperfusion. Recent studies have shown that RIPC has neuroprotective effects, but its mechanisms are not well elucidated. The present study aimed to determine whether activation of KATP channels in remote renal preconditioning decreases hippocampus damage induced by global cerebral ischemia. RIPC was induced by ischemia of the left renal artery (IPC); 24 h later, global cerebral ischemia reperfusion (IR) was induced by common carotid arteries occlusion. 5hydroxydecanoate (5HD) and glibenclamide (Gli) were injected before of IPC. The levels of malondialdehyde (MDA) and catalase (CAT) activity were assessed in hippocampus. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was assessed to detect apoptotic cells in hippocampus. RIPC inhibited apoptosis by decreasing positive TUNEL cells (P < 0.05). KATP channels blocking with 5HD and Gli markedly increased apoptosis in hippocampal cells in RIPC group (P < 0.001). RIPC decreased MDA level and increased CAT activity in ischemic hippocampus (P < 0.01). Also, 5HD and Gli inhibited the effect of RIPC on MDA level and CAT activity (P < 0.05). The present study shows that RIPC can effectively attenuate programmed cell death, increase activity of CAT, and reduce MDA levels. Blocking of KATP channels inhibited the protective effects of RIPC. PMID:26254913

  10. Nature vs Nurture: Effects of Learning on Evolution

    NASA Astrophysics Data System (ADS)

    Nagrani, Nagina

    In the field of Evolutionary Robotics, the design, development and application of artificial neural networks as controllers have derived their inspiration from biology. Biologists and artificial intelligence researchers are trying to understand the effects of neural network learning during the lifetime of the individuals on evolution of these individuals by qualitative and quantitative analyses. The conclusion of these analyses can help develop optimized artificial neural networks to perform any given task. The purpose of this thesis is to study the effects of learning on evolution. This has been done by applying Temporal Difference Reinforcement Learning methods to the evolution of Artificial Neural Tissue controller. The controller has been assigned the task to collect resources in a designated area in a simulated environment. The performance of the individuals is measured by the amount of resources collected. A comparison has been made between the results obtained by incorporating learning in evolution and evolution alone. The effects of learning parameters: learning rate, training period, discount rate, and policy on evolution have also been studied. It was observed that learning delays the performance of the evolving individuals over the generations. However, the non zero learning rate throughout the evolution process signifies natural selection preferring individuals possessing plasticity.

  11. The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients.

    PubMed

    Kiser, J J; Carten, M L; Aquilante, C L; Anderson, P L; Wolfe, P; King, T M; Delahunty, T; Bushman, L R; Fletcher, C V

    2008-02-01

    We determined the effects of lopinavir/ritonavir on tenofovir renal clearance. Human immunodeficiency virus-infected subjects taking tenofovir disoproxil fumarate (TDF) were matched on age, race, and gender and were enrolled into one of the following two groups: group 1: subjects taking TDF plus lopinavir/ritonavir plus other nucleoside reverse transcriptase inhibitors (NRTIs); group 2: subjects taking TDF plus NRTIs and/or non-NRTIs but no protease inhibitors. Twenty-four-hour blood and urine collections were carried out in subjects for tenofovir quantification. Drug transporter genotype associations with tenofovir pharmacokinetics were examined. In 30 subjects, median (range) tenofovir apparent oral clearance, renal clearance, and fraction excreted in urine were 34.6 l/h (20.6-89.5), 11.3 l/h (6.2-22.6), and 0.33 (0.23-0.5), respectively. After adjusting for renal function, tenofovir renal clearance was 17.5% slower (P=0.04) in subjects taking lopinavir/ritonavir versus those not taking a protease inhibitor, consistent with a renal interaction between these drugs. Future studies should clarify the exact mechanism and whether there is an increased risk of nephrotoxicity. PMID:17597712

  12. Antitumor effect and biological pathways of a recombinant adeno-associated virus as a human renal cell carcinoma suppressor.

    PubMed

    Chen, Jie; Ruan, Xiyun; Wang, Shaomei; Zhang, Bin; Liu, Bo; Sun, Zeqiang; Liu, Qingyong

    2014-11-01

    The aims of this work are to study the antitumor effect of the adeno-associated virus on the xenografted tumors of chick embryo chorioallantoic membrane and predict potential genes and biological pathways which are associated with renal cell carcinoma. The adeno-associated virus NT4-TAT-6 × His-VHLbeta was constructed and identified. Then, chick embryos with xenografted tumor were divided into three groups and respectively inoculated with rAAV/NT4-TAT-6 × His-VHLbeta (group A), empty virus (group B), and phosphate-buffered saline (group C, the control subject). Antitumor effect in each group was investigated by means of immunofluorescence observation. Genes interacted with von Hippel-Lindau were screened by Search Tool for the Retrieval of Interacting Genes/Proteins database, while pathway analysis were performed based on Kyoto Encyclopedia of Genes and Genomes. The growth of xenografted tumors inoculated with recombinant adeno-associated virus was slower than the control subjects. The tumor volumes of group A showed significant difference compared with group B and group C (P < 0.05). Growth of xenografted tumors which administered with the recombinant adeno-associated virus was inhibited. Among the protein-protein interaction network, TCEB2, HIF1A, TCEB1, CUL2, RBX1, and PHF17 were hub genes which might be involved in the development of renal cell carcinoma. The most significant signaling pathway was renal cell carcinoma. In this paper, we constructed and identified the recombinant adeno-associated virus NT4-TAT-6 × His-VHLbeta and studied the antitumor effect of the adeno-associated virus on xenografted tumors of chicken embryo chorioallantoic membrane. In addition, genes in the protein-protein interaction network which are associated with renal cell carcinoma were revealed and the biological pathway of renal cell carcinoma was identified. Our results provide a gene-therapeutic agent for the treatment of human renal cell carcinoma. PMID:25091575

  13. The effect of surgery on the renal excretion of beta 2-microglobulin.

    PubMed

    Walenkamp, G H; Vree, T B; Guelen, P J; Jongman-Nix, B

    1983-03-28

    Surgical trauma causes an increase in the renal excretion rate of beta 2-microglobulin whilst creatinine excretion is not influenced. The increase in the renal excretion rate of beta 2-microglobulin is probably the result of an increased release of beta 2-microglobulin by the cells which exceeds a maximum in the active tubular reabsorption of the compound by the proximal tubule cell. The renal excretion of beta 2-microglobulin is proportional to the relative clinical trauma score. PMID:6189646

  14. Renal and systemic acid-base effects of chronic dichloroacetate administration in dogs.

    PubMed

    Hulter, H N; Glynn, R D; Sebastian, A

    1980-10-01

    Dichloroacetate (DCA) increases metabolic disposal of lactic acid secondary to activation of pyruvate dehydrogenase and consequent acceleration of pyruvate oxidation. DCA has thus been proposed as a therapeutic agent for clinical states of lactic acidosis. Yet, DCA has a potential metabolic acidosis-producing effect by virtue of reported effects of (A) increasing blood ketoacid concentration, (B) decreasing tubular reabsorption of filtered ketoacid anions, and (C) decreasing renal NH3 production. In the present study chronic administration of DCA, 50 mg/kg p.o. daily for 6-8 days, resulted in a cumulative increase in renal net acid excretion (NAE) (sigma delta NAE, +61 meq, p < 0.05). The increase in NAE was accounted for entirely by increased NH4+ excretion. Production of ammonia by the kidney appeared to be increased since the increased excretion of NH4+ was accompanied by an increase in urine pH (delta UpH, +0.18 +/- 0.07, p < 0.05). The increase in NAE was accompanied by a nearly identical increase in urinary anion gap (UAG) (UAG = [NH4+ + Na+ + K+] - [Cl- + HCO3- + HPO4(2-) + H2PO4-]). The increase in UAG was caused by increased urinary total organic anions, accounted for at least in part by a significant increase in urinary acetoacetate. No significant increase in urinary potassium or sodium excretion occurred. A change in plasma acid-base composition occurred that was consistent with a mild respiratory acidosis without associated primary metabolic acidosis or alkalosis. These findings indicate that chronic DCA administration results in (1) increased steady state endogenous noncarbonic organic acid production, and (2) retention of carbonic acid. Further investigation of the potential metabolic and respiratory acidosis-producing effects of DCA is required to determine its clinical efficacy in the treatment of clinical lactic acidosis. PMID:7421587

  15. [Protective effect of Angelica sinensis polysaccharides on subacute renal damages induced by D-galactose in mice and its mechanism].

    PubMed

    Fan, Yan-ling; Xia, Jie-yu; Jia, Dao-yong; Zhang, Meng-si; Zhang, Yan-yan; Wang, Lu; Huang, Guo-ning; Wang, Ya-ping

    2015-11-01

    To explore the protective effect of Angelica sinensis polysaccharides(ASP) on subacute renal damages induced by D-galactose in mice and its mechanism. Male C57BL/6J mice were randomly divided into 3 groups, with 10 mice in each group. The D-galactose model group was subcutaneously injected with D-galactose (120 mg x kg(-1)), qd x 42; the ASP + D-galactose model group was intraperitoneally injected with ASP since the 8th day of the replication of the D-galactose model, qd x 35; and the normal control group was subcutaneously injected with saline at the same dose and time. On the 2nd day of after the injection, the peripheral blood was collected to measure the content of BUN, Crea, UA, Cys-C; paraffin sections were made to observe the renal histomorphology by HE staining; senescence-associated β-g-alactosidase (SA-β-Gal) stain was used to observe the relative optical density (ROD) in renal tissues; transmission electron microscopy was assayed to observe the renal ultrastructure; the renal tissue homogenate was prepared to measure the content of SOD, GSH-PX, MDA; the content of AGEs and 8-OH-dG were measured by ELISA. According to the result, compared with the D-galactose model group, the ASP + D-galactose model group showed obviously decreases in the content of BUN, Crea, UA, Cysc, AGES, 8-OH-dG, the number of hardening renal corpuscle, renal capsular space and renal tubular lumen, ROD of SA-β-Gal staining positive kidney cells, mesangial cells, basement membrane thickness, podocyte secondary processes fusion and MDA and increases in the number of normal renal corpuscle, ribosome and rough endoplasmic reticulum in podocytes, the activity of SOD and GSH-PX. In Conclusion, A. sinensis polysaccharides can antagonize kidney subacute damages induced by D-galactose in mice. Its protective mechanism may be correlated with the inhibition of the oxidative stress injury. PMID:27071262

  16. Effects of ANF infusion on the renal responses to lower-body negative pressure in humans.

    PubMed

    Mauran, P; Pham, I; Sediame, S; Jolly, D; Chabrier, P E; Carayon, A; Andrivet, P; Adnot, S

    1998-05-01

    To investigate the role of atrial natriuretic factor (ANF) in renal responses to a decrease in central blood volume, we examined the effects of ANF infusion on renal function and hormones during prolonged lower-body negative pressure (LBNP). Ten healthy volunteers participated in two experimental sequences, each comprising a 120-min baseline period followed by the application of -20 mm Hg LBNP for 90 min. During one of the two sequences, ANF was infused throughout LBNP application at the constant rate of 2.5 ng/kg/min. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by using inulin and p-aminohippuric acid clearance techniques. LBNP induced a significant decrease in ERPF (534 +/- 28 to 457 +/- 26 ml/min; p < 0.05), GFR (120 +/- 2.5 to 112 +/- 2.5 ml/min; p < or = 0.01), in urine excretion (12 +/- 0.9 to 5.6 +/- 0.5 ml/min; p < 0.001), in sodium excretion (0.36 +/- 0.03 to 0.30 +/- 0.02 mmol/min; p < 0.05), and in plasma ANF (19 +/- 3 to 11 +/- 2 pg/ml; p = 0.001) concomitant with an increase in plasma renin activity (PRA; 0.48 +/- 0.09 to 0.87 +/- 0.16 ng/ml/h; p = 0.01) and of forearm vascular resistance (FVR; p < 0.05). The combination of ANF infusion with LBNP led to a slight increase in plasma ANF from baseline (from 20 +/- 2 to 28 +/- 3 pg/ml; p < 0.05). Compared with values obtained during LBNP with saline vehicle infusion, values obtained during LBNP with ANF infusion were similar for ERPF (463 +/- 23 vs. 457 +/- 26 ml/min), for GFR (111 +/- 2 vs. 112 +/- 2 ml/min), and for urine excretion (7 +/- 0.6 vs. 5.6 +/- 0.5 ml/min; p = 0.07), but greater for fractional excretion of sodium (2.38 +/- 0.25% vs. 1.91 +/- 0.11%; p < 0.05) and FVR (p < 0.05), and smaller for PRA (0.49 +/- 0.1 vs. 0.87 +/- 0.16 ng/ml/h; p < 0.01). These data show that ANF infusion attenuates the antinatriuretic effect of low-level LBNP and its PRA-increasing effects without altering renal hemodynamic responses to LBNP, although there is a decrease in

  17. Combined treatment with vitamin E and gefitinib has synergistic effects to inhibit TGF-β1-induced renal fibroblast proliferation.

    PubMed

    Yiang, Giou-Teng; Chen, Jen-Ni; Lin, Pei-Shiuan; Liu, Hsiao-Chun; Chen, Shu-Ying; Wei, Chyou-Wei

    2016-06-01

    Renal fibroblast proliferation is key in renal fibrosis and chronic kidney disease. Transforming growth factor-β1 (TGF-β1) has been demonstrated to be an important factor that induces cell proliferation in renal fibroblasts. Epidermal growth factor receptor (EGFR) is also recognized as a factor promoting renal fibroblast proliferation. In addition, mitogen‑activated protein kinase signaling pathways are associated with TGF‑β1‑ and EGFR‑induced cell proliferation. Gefitinib, an EGFR tyrosine kinase inhibitor, is predominantly used as an anti‑tumor therapeutic agent in clinical therapeutic strategies. However, gefitinib has been suggested to exert anti‑proliferative effects on renal fibroblasts, however, high‑dose gefitinib may result in serious side effects. The present study aims to determine whether low‑dose gefitinib reduces gefitinib‑induced side effects and maintains the anti‑proliferative effects on renal fibroblasts. TGF‑β1 promotes cell proliferation in renal fibroblasts, and the current study demonstrates that low‑dose gefitinib treatment exhibits anti‑proliferative effects similar to those of high‑dose gefitinib treatment. Thus, although high‑dose gefitinib is a conventional anti‑tumor drug, low‑dose gefitinib may be of use in renal fibrosis treatment. Furthermore, the present study demonstrates that a combined treatment with low-dose gefitinib and vitamin E has synergistic effects that reduce TGF‑β1‑induced fibroblast proliferation, cell-cycle arrest and the ERK phosphorylation pathway. PMID:27109695

  18. Effects of lead on the renal response to extracellular volume expansion

    SciTech Connect

    Powers, W.J. Jr.

    1982-01-01

    Subacute lead exposure has been observed to inhibit the natriuretic response to isotonic saline expansion in adult female rats. The study was conducted in three major phases: 1) characterization of lead effects on the natriuretic response to volume expansion; 2) effects of lead on the glomerular filtration rate and plasma aldosterone concentration; and 3) effects of Amiloride (a weak diuretic) on the antinatriuretic actions of lead. Three weeks' exposure to 0.5% lead acetate in drinking water resulted in a moderately high blood lead concentration of 56.9 ug/100 mL and up to a 60% inhibition of the natriuretic response. This capability of lead to inhibit natriuresis following volume expansion (an induced stress) may be a more sensitive index of lead poisoning than alterations of renal function in nonstressed animals. Lead exposure had no detectable effect on plasma adosterone concentrations. Therefore lead-induced alterations of GFR and plasma aldosterone levels could be ruled out as mechanisms of action for the observed antinatriuretic effects. A physiologically effective dose of Amiloride was found capable of completely blocking the antinatriuretic effect of lead. In the lead-poisoned animals, Amiloride caused a two-fold increase in water and electrolyte excretion while having minimal effects on the non-lead poisoned group water and electrolyte excretion. It is concluded that lead inhibits the natriuretic response to saline expansion via some unexplained third factor mechanism.

  19. Effect of Sodium Selenite on Pathological Changes and Renal Functions in Broilers Fed a Diet Containing Aflatoxin B1

    PubMed Central

    Liang, Na; Wang, Fengyuan; Peng, Xi; Fang, Jing; Cui, Hengmin; Chen, Zhengli; Lai, Weimin; Zhou, Yi; Geng, Yi

    2015-01-01

    To evaluate the renal toxicity of dietary aflatoxin B1 (AFB1) and ameliorating effects of added dietary sodium selenite in broiler, renal histopathological changes, ultrastructural changes, and renal function parameters were monitored at 7, 14, and 21 days of age. Two hundred one-day-old healthy male Avian broilers were divided into four groups, namely control group, AFB1 group (0.3 mg/kg AFB1), +Se group (0.4 mg/kg Se), and AFB1+Se group (0.3 mg/kg AFB1+0.4 mg/kg Se). Compared with that of the control group, the relative weight of kidney was increased in the AFB1 group. There were no significant differences between the AFB1+Se group and the control group. By histopathological observation, the renal epithelia were swelling and necrosis at 7 and 21 days of age. Ultrastructurally, the lipid droplets and expanded endoplasmic reticulum appeared in the plasma of epithelia cells in the AFB1 group. Enlarged mitochondria with degenerated cristae were observed in the +Se group. Compared with the control group, the contents of serum creatinine and serum uric acid in the AFB1 group were increased, while the activity of renal Na+-K+ ATPase was decreased. When 0.4 mg/kg selenium was added into the diet containing 0.3 mg/kg AFB1, there were no obvious histological changes in the AFB1+Se group, and the contents of the serum creatinine and serum uric acid contents and the activity of renal Na+-K+ ATPase were close to those in the control group. In conclusion, sodium selenite exhibited protective effects on AFB1-induced kidney toxicity in broilers. PMID:26371027

  20. The protective effects of the traditional Chinese herbs against renal damage induced by extracorporeal shock wave lithotripsy: a clinical study.

    PubMed

    Sheng, Binwu; He, Dalin; Zhao, Jun; Chen, Xingfa; Nan, Xunyi

    2011-04-01

    Extracorporeal shock wave lithotripsy (ESWL)-induced renal damage can occur as a result of multiple mechanisms. We have reported previously that Astragalus membranaceus, Salvia miltiorrhiza, a decoction of six drugs containing rhizoma Rehmanniae preparata and supplements of a few traditional Chinese medicinal herbs for invigorating the kidney and excreting calculus, have a protective effect on renal injury induced by high-energy shock waves (HESW) in rabbits. In this clinical study we further investigate the protective effects of these traditional Chinese herbs against renal damage induced by ESWL. Sixty consenting patients with renal calculus who underwent ESWL treatment were included and randomly assigned to the medication group or control group. Post-ESWL plasma nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), and serum tumor necrosis factor α (TNF-α) increased significantly in the controls (P < 0.05), while in the medication group, slightly but not significantly elevated levels of plasma ET-1, NO, and serum TNF-α were found. The difference between the groups was statistically significant (P < 0.05). The levels of superoxide dismutase (SOD) decreased gradually in the controls, reaching a trough 72 h after ESWL (P < 0.05), while in the treated group it was unchanged, and remained at a level higher versus the controls (P < 0.05). Plasma NO peaked twice by 72 h and at 1 week in the controls (P < 0.05). Urinary enzymes and β(2)-microglobulin increased significantly and peaked by 24 h and immediately after ESWL (P < 0.05). These values were greater in the controls, and the difference was statistically significant (P < 0.05). This study demonstrates that the preparations of traditional Chinese medicines for invigorating the kidney and excreting calculus can reduce renal tubular damage induced by ESWL, and can shorten the recovery time of renal tubules in human subjects. PMID:20607528

  1. Effect of the number of blades on propeller wake evolution

    NASA Astrophysics Data System (ADS)

    Felli, Mario; Guj, Giulio; Camussi, Roberto

    2008-03-01

    The effect of the number of blades on wake evolution was investigated on three propellers having the same blade geometry but different numbers of blades. The experiments concerned velocity measurements along nine transversal planes of the wake by LDV phase-sampling techniques. The study was performed with all the propellers having the same tip vortex intensity. In addition, high-speed visualizations were carried out to analyze the main features of propeller wake evolution in the transition and in the far wake. Aspects concerning wake evolution were pointed out, with particular emphasis on the instability mechanism of the propeller slipstream and on its correlation with the blade-to-blade interaction phenomenon.

  2. Effects of Renin-Angiotensin-Aldosterone System Blockade in Patients with End-Stage Renal Disease.

    PubMed

    Slomka, Teresa; Lennon, Emily S; Akbar, Hina; Gosmanova, Elvira O; Bhattacharya, Syamal K; Oliphant, Carrie S; Khouzam, Rami N

    2016-03-01

    Blockers of the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are routinely used in patients with chronic kidney disease because of their cardiovascular (CV) and renoprotective effects. However, there are no uniform recommendations about RAAS blockers for CV protection in the end-stage renal disease (ESRD) population other than the preferred drug class for blood pressure control. This uncertainty stems from the fact that patients with ESRD were generally excluded from randomized controlled trials evaluating the cardioprotective benefits of RAAS blockers. It is important to weigh the potential harms associated with the use of RAAS blockers, such as electrolyte disturbances and worsening anemia, with their role in protection of residual kidney function, alleviation of thirst and potential CV benefits. The objective of this review is to summarize the current knowledge about the use of RAAS blockers in patients with ESRD. PMID:26992264

  3. The effect of anesthetization and urinary bladder catheterization on renal function of rainbow trout

    USGS Publications Warehouse

    Hunn, J.B.; Willford, W.A.

    1970-01-01

    1. Rainbow trout were anesthetized with MS-222 (Sandoz) or methylpentynol and catheterized. Urine was collected at selected intervals up to 48 hr. 2. Effects of MS-222 anesthesia on urine flow and composition were isolated from the stress of catheterization by re-anesthetizing the fish 18 to 20 hr post catheterization. 3. Urine output patterns were similar following MS-222 or methylpentynol anesthesia and catheterization. Highest urine flows were measured 4 to 8 hr post treatment. The highest urine output after re-anesthetization with MS-222 was observed 2 to 4 hr post-anesthesia. 4. Highest concentrations of Na2+, K+, Ca2+, Cl- and inorganic PO4 in the urine were measured in the first 2 hr after anesthesia and catheterization. 5. Flow rates and chemical composition of urine indicate that "normal" renal function is re-established 12 to 24 hr post-treatment.

  4. Effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injuries in Dahl salt-sensitive rats.

    PubMed

    Konda, Tomoyuki; Enomoto, Azusa; Takahara, Akira; Yamamoto, Hiroshi

    2006-05-01

    The sympathetic nerve activity plays an important role on the renal function through the vasoactive system and the renin-angiotensin system. Although interest in the renal protective effects of anti-sympathetic agents has been increased, there are not enough data to clarify this efficiency. Therefore, we investigated the effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injury in Dahl salt-sensitive (Dahl S) rats. Male Dahl S rats (6 weeks of age) were fed a high salt (4% NaCl) diet. They were divided into groups with similar blood pressure at 12 weeks of age and they received vehicle (n=7) or cilnidipine (30 mg/kg/d as food admix, n=9) for 8 weeks. Cilnidipine treatment suppressed the increase in systolic blood pressure. Although urinary protein excretion was not influenced, cilnidipine inhibited the increase in blood urea nitrogen and decrease in creatinine clearance. Histological investigation revealed that progression of glomerular sclerosis was inhibited in cilnidipine treatment group. Of notes, cilnidipine reduced plasma norepinephrine level and plasma rennin activity compared with vehicle-treated Dahl S rats. These data indicated that cilnidipine has suppressive effects against progressive renal injury in Dahl S rats. This effect is not only explained by the L-type calcium channel blocking action that lowered blood pressure, but also partially explained by the N-type calcium channel blocking action that lead to suppression of the sympathetic nerve activity and renin-angiotensin system. PMID:16651722

  5. Renal arteriography

    MedlinePlus

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Update Date 4/7/2014 Updated by: Jason ... Failure Kidney Tests X-Rays Browse the Encyclopedia A. ...

  6. Renal venogram

    MedlinePlus

    ... 2008:chap 6. Rankin S. Renal parenchymal disease, including renal failure, renovascular disease and transportation. In: Grainger RC, Allison D, Adam, Dixon AK, eds. Diagnostic Radiology: A Textbook of Medical Imaging . 5th ed. New York, NY: Churchill Livingstone; 2008:chap 39. Read ... arteriography Renal vein thrombosis Tumor Venogram Wilms ...

  7. Fluid Secretion in Isolated Proximal Straight Renal Tubules EFFECT OF HUMAN UREMIC SERUM

    PubMed Central

    Grantham, Jared J.; Irwin, Richard L.; Qualizza, Patti B.; Tucker, Donald R.; Whittier, Frederick C.

    1973-01-01

    We have examined the effect of normal and uremic human sera on the transtubular flow of fluid in isolated perfused segments of rabbit proximal convoluted and straight renal tubules. Proximal convoluted and straight tubules absorbed fluid from the lumen when the external bath was normal rabbit serum. Normal human sera in the bath depressed net fluid absorption in both tubular segments, but more importantly, uremic human serum caused proximal straight tubules to secrete fluid into the lumen. Fluid secretion was also demonstrated indirectly by observing in nonperfused proximal straight, but not proximal convoluted tubules, that the normally collapsed lumens opened widely in uremic serum. Nonperfused proximal straight tubules developed expanded lumens even after a 25-fold dilution of human uremic serum with normal rabbit serum, whereas lumen expansion occurred only in undiluted normal human serum, on the average. Serum from acutely uremic rabbits possessed secretory activity but normal rabbit serum did not. The secretory effect of uremic sera in proximal straight tubules was inhibited by cooling and ouabain and probenecid. The secretory activity of uremic sera was removed by dialysis, but not by freezing or boiling. Para-aminohippurate and benzoate caused fluid secretion in proximal straight tubules but urea, creatinine, guanidinosuccinate, and urate did not. On the basis of these results, we suggest that the secretory factor in serum may be a substance or group of substances possibly related to the hippurate class of organic molecules that are accumulated to relatively high concentrations in renal failure. The secretory material in the serum of uremic patients may significantly influence the transport of salt and water in relatively intact residual nephrons. Images PMID:4738063

  8. The Ginkgo biloba Extract Reverses the Renal Effects of Titanium Dioxide Nanoparticles in Adult Male Rats.

    PubMed

    Escárcega-González, Carlos Enrique; Reynoso-Andeola, Irma Guadalupe; Jaramillo-Juárez, Fernando; Martínez-Ruvalcaba, Haydée; Posadas Del Rio, Francisco A

    2016-01-01

    The Ginkgo biloba extract (GbE) is a commercial product used as a nutraceutic herbal remedy in Europe and US. It contains 27% of the polyphenols isorhamnetin, kaempferol, and quercetin, as antioxidants. We used male adult Wistar rats (200-300 g), divided into four groups: control group (treated with 5.0 mg/kg of sodium chloride, intravenous), titanium dioxide nanoparticles (TiO2-NPs) group (5.0 mg/kg, intravenous), GbE group (10 mg/kg, intraperitoneal), and GbE + TiO2-NPs group (treated 24 h before with 10 mg/kg of GbE, intraperitoneal), followed, 24 h later, by 5.0 mg/kg of TiO2-NPs intravenously. The statistical analysis was performed using Student's t-test for grouped data with ANOVA posttest. The GbE protected renal cells against the effects of TiO2-NPs because it reversed the increased activity of γ-glutamyltranspeptidase and the enzymatic activity of dipeptidylaminopeptidase IV at all times tested (0-5, 5-24, 24-48, and 48-72 h). Also it reversed the glucosuria, hypernatriuria, and urine osmolarity at three times tested (5-24, 24-48, and 48-72). Thus, we conclude that GbE has a beneficial activity in the cytoplasmic membranes of brush border cells on the renal tubules, against the adverse effects that can be produced by some xenobiotics in this case the TiO2-NPs, in experimental rats. PMID:27042354

  9. The Ginkgo biloba Extract Reverses the Renal Effects of Titanium Dioxide Nanoparticles in Adult Male Rats

    PubMed Central

    Reynoso-Andeola, Irma Guadalupe; Jaramillo-Juárez, Fernando; Martínez-Ruvalcaba, Haydée; Posadas del Rio, Francisco A.

    2016-01-01

    The Ginkgo biloba extract (GbE) is a commercial product used as a nutraceutic herbal remedy in Europe and US. It contains 27% of the polyphenols isorhamnetin, kaempferol, and quercetin, as antioxidants. We used male adult Wistar rats (200–300 g), divided into four groups: control group (treated with 5.0 mg/kg of sodium chloride, intravenous), titanium dioxide nanoparticles (TiO2-NPs) group (5.0 mg/kg, intravenous), GbE group (10 mg/kg, intraperitoneal), and GbE + TiO2-NPs group (treated 24 h before with 10 mg/kg of GbE, intraperitoneal), followed, 24 h later, by 5.0 mg/kg of TiO2-NPs intravenously. The statistical analysis was performed using Student's t-test for grouped data with ANOVA posttest. The GbE protected renal cells against the effects of TiO2-NPs because it reversed the increased activity of γ-glutamyltranspeptidase and the enzymatic activity of dipeptidylaminopeptidase IV at all times tested (0–5, 5–24, 24–48, and 48–72 h). Also it reversed the glucosuria, hypernatriuria, and urine osmolarity at three times tested (5–24, 24–48, and 48–72). Thus, we conclude that GbE has a beneficial activity in the cytoplasmic membranes of brush border cells on the renal tubules, against the adverse effects that can be produced by some xenobiotics in this case the TiO2-NPs, in experimental rats. PMID:27042354

  10. Hyperphosphataemia sensitizes renally impaired rats to the profibrotic effects of gadodiamide

    PubMed Central

    Fretellier, N; Idée, JM; Bruneval, P; Guerret, S; Daubiné, F; Jestin, G; Factor, C; Poveda, N; Dencausse, A; Massicot, F; Laprévote, O; Mandet, C; Bouzian, N; Port, M; Corot, C

    2012-01-01

    BACKGROUND AND PURPOSE Hyperphosphataemia is common in patients with nephrogenic systemic fibrosis (NSF). NSF has been linked to administration of gadolinium (Gd) chelates (GCs) and elevated serum phosphate levels accelerate the release of Gd from linear, non-ionic GCs but not macrocyclic GCs. Hence, we determined whether hyperphosphataemia is a cofactor or risk factor for NSF by investigating the role of hyperphosphataemia in renally impaired rats. EXPERIMENTAL APPROACH Firstly, the clinical, pathological and bioanalytical consequences of hyperphosphataemia were investigated in subtotal nephrectomized (SNx) Wistar rats following i.v. administration of the non-ionic, linear GC gadodiamide (5 × 2.5 mmol·kg−1·day−1). Secondly, the effects of several GCs were compared in these high-phosphate diet fed rats. Total Gd concentration in skin, femur and plasma was measured by inductively coupled plasma mass spectrometry (ICP-MS) and free Gd3+ in plasma by liquid chromatography coupled to ICP-MS. Relaxometry was used to measure dissociated Gd in skin and bone. KEY RESULTS Four out of seven SNx rats fed a high-phosphate diet administered gadodiamide developed macroscopic and microscopic (fibrotic and inflammatory) skin lesions, whereas no skin lesions were observed in SNx rats treated with saline, the other GCs and free ligands or in the normal diet, gadodiamide-treated group. Unlike the other molecules, gadodiamide gradually increased the r1 relaxivity value, consistent with its in vivo dissociation and release of soluble Gd. CONCLUSIONS AND IMPLICATIONS Hyperphosphataemia sensitizes renally impaired rats to the profibrotic effects of gadodiamide. Unlike the other GCs investigated, gadodiamide gradually dissociates in vivo. Our data confirm that hyperphosphataemia is a risk factor for NSF. PMID:21740412

  11. Dissimilar effects of chronic treatment with aspirin, flubiprofen and indomethacin on renal prostaglandins

    SciTech Connect

    Quilley, C.P.; McGiff, J.C.; Quilley, J.

    1986-03-01

    Inhibition of prostaglandin (PG) excretion is not sustained during long-term aspirin administration. The authors compared the effects of 9d treatment of SHR rats with aspirin (A), 200 mg/kg/d s.c., flubiprofen (F), 2.5 mg/kg/12h s.c., and indomethacin (I), 2.5 mg/kg/12 s.c. on excretion of radioimmunoassayable PGE/sub 2/ and PGF/sub 2..cap alpha../. Conversion of 1-(/sup 14/C) arachidonic acid (AA) by renal papillae was also examined. In vehicle-treated control rats (C) PGF/sub 2..cap alpha../ excretion varied from 32.2 +/- 6.2 (mean +/- SEM) to 41.6 +.- 7.3 ng/6h, 3-fold higher than that of PGE/sub 2/. Within 6h of administration all 3 drugs reduced excretion of PGF/sub 2..cap alpha../ and PGE/sub 2/ to less than 20% and 35% of C rats. Although urinary concentrations of PGF/sub 2..cap alpha../ and PGE/sub 2/ in A-treated rats remained depressed, a 2-fold increase in urine volume resulted in excretion rates similar to C rats. In contrast, urine volume in I- and F-treated rats was unaffected while PGF/sub 2..cap alpha../ and PGE/sub 2/ excretion rates in I-treated rats were 50''% of C rats and were also lower than control in F-treated rats. Paradoxically, metabolism of AA to PGs by by renal papillae dissected on day 10, 2-4h after the last drug dose, was markedly inhibited by A (PGF/sub 2..cap alpha../ by 62% and PGE/sub 2/ by 82%), but unaffected by I and F. As the effects of cyclooxygenase inhibitors differ on in vivo and indices of PG production, their intended action should be verified by measuring PG levels in biological fluids.

  12. Effects of Chronic Renal Failure on Brain Cytochrome P450 in Rats.

    PubMed

    Naud, Judith; Harding, Jessica; Lamarche, Caroline; Beauchemin, Stephanie; Leblond, Francois A; Pichette, Vincent

    2016-08-01

    Chronic renal failure (CRF) impedes renal excretion of drugs and their metabolism by reducing the expression of liver cytochrome P450 (P450). Uremic serum contains factors, such as parathyroid hormone (PTH), that decrease liver P450s. The P450s are also involved in the metabolism of xenobiotics in the brain. This study investigates: 1) the effects of CRF on rat brain P450, 2) the role of PTH in the downregulation of brain P450s in CRF rats, and 3) the effects of PTH on P450s in astrocytes. Protein and mRNA expression of P450s were assessed in the brain of CRF and control (CTL) rats, as well as from CTL or CRF rats that underwent parathyroidectomy (PTX) 1 week before nephrectomy. CYP3A activity was measured using 3-[(3, 4-difluorobenzyl) oxy]-5, 5-dimethyl-4-[4-methylsulfonyl) phenyl] furan-2(5H)-1 metabolism in brain microsomal preparation. CYP3A protein expression was assessed in primary cultured astrocytes incubated with serum obtained from CRF or CTL rats or with PTH. Significant downregulations (≥40%) of CYP1A, CYP2C11, and CYP3A proteins were observed in microsomes from CRF rat brains. CYP3A activity reduction was also observed. CYP3A expression and activity were unaffected in PTX-pretreated CRF rats. Serum of PTX-treated CRF rats had no impact on CYP3A levels in astrocytes compared with that of untreated CRF rats. Finally, PTH addition to normal calf serum induced a reduction in CYP3A protein similar to CRF serum, suggesting that CRF-induced hyperparathyroidism is associated with a significant decrease in P450 drug-metabolizing enzymes in the brain, which may have implications in drug response. PMID:27271372

  13. Effect of Momordica dioica Roxb on gentamicin model of acute renal failure.

    PubMed

    Jain, Avijeet; Singhai, A K

    2010-09-01

    The ethanolic extract of the fruits of Momordica dioica was studied for its protective and curative effect against gentamicin-induced acute renal injury in albino rats of both sexes. Gentamicin intoxicated group showed significant increase in blood urea (69.48 +/- 4.34) and serum creatinine (3.017 +/- 0.208) from normal levels 33.72 +/- 1.92 and 0.818 +/- 0.073, respectively, in control group. In the preventive regimen, the extract at dose levels of 200 mg kg(-1) showed significant reduction in the elevated blood urea (47.93 +/- 2.46) and serum creatinine (2.067 +/- 0.1745), respectively. This treatment normalised the histopathological changes compared to the intoxicated group. In the curative regimen at 200 mg kg(-1) blood urea was found to be 48.21 +/- 2.36 and serum creatinine level was 2.050 +/- 0.183, which revealed significant curative effect. In vivo antioxidant and free radial scavenging activities were also determined. The maximum free radical scavenging activity with ethanolic extract was the basis of selection of this extract for in vivo study. Reduced glutathione (GSH) level was significantly (p < 0.05) increased in the extract treated groups whereas malondialdehyde (MDA) was reduced significantly (p < 0.05). High content of flavonoids and phenolic compounds was found in ethanolic extract, which may be responsible for free radical activity. The findings suggest that the ethanol extract of Momordica dioica seeds possesses marked nephroprotective and curative activities without any toxicity due to its antioxidant activity and could offer a promising role in the treatment of acute renal injury caused by nephrotoxin-like gentamicin. PMID:19241280

  14. Feedback control of temperature evolution in rabbit kidney in vivo using MRI guided focused ultrasound. Application to renal VX2 carcinoma ablation

    NASA Astrophysics Data System (ADS)

    Delemazure, A. S.; Salomir, R.; Grenier, N.; Palussière, J.; Deminière, C.; Mougenot, C.; Moonen, C. W.

    2005-03-01

    A significant number of patients with small renal tumours may get benefit from in situ thermo-ablation techniques. Focused ultrasound is a non-invasive approach which offers excellent flexibility. On the other hand, real time MR thermometry is a valuable tool for monitoring and controlling therapy. In this study, coupling of focused ultrasound with PRF-based, respiratory-gated MR thermometry was used to provide temperature feedback control for local hyperthermia in the rabbit kidney. Two heating protocols were initially used in healthy kidneys (medulla and cortex): 1. fixed focal point heating; 2. spiral trajectories of the focal point. Further, five VX2 renal carcinomas were treated with multiple focal point heating in each tumour. Post-treatment MRI follow up and post mortem histology were performed. The shape and size of the lesions (MRI, histology) were compared to the calculated thermal dose map. The standard deviation of the MR thermometry ranged from 0.5°C to 1°C. The temperature controller matched the objective curve with approximately 1°C precision (fixed focal point mode). Several technical and physiological difficulties for spiral heating could not be overcome with the available setup. Thermal ablation with temperature feedback control in healthy and tumour bearing kidney was demonstrated to be feasible and effective, despite specific challenges (deep seated organ, respiratory motion, high blood perfusion).

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

    PubMed

    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. PMID:26429932

  16. Brazilin exerts protective effects against renal ischemia-reperfusion injury by inhibiting the NF-κB signaling pathway

    PubMed Central

    JIA, YANYAN; ZHAO, JINYI; LIU, MEIYOU; LI, BINGLING; SONG, YING; LI, YUWEN; WEN, AIDONG; SHI, LEI

    2016-01-01

    Renal ischemia-reperfusion (I/R) injury is associated with high morbidity and mortality as there is currently no available effective therapeutic strategy with which to treat this injury. Thus, the aim of this study was to investigate the potential protective effects of brazilin, a major active component of the Chinese medicine Caesalpinia sappan L., against renal I/R injury in vitro and in vivo. Rats were subjected to removal of the right kidney and I/R injury to the left kidney (ischemia for 45 min followed by reperfusion for 24 h). Treatment with brazilin (30 mg/kg, administered intravenously at 30 min prior to ischemia) led to the reversal of I/R-induced changes in serum creatinine (Scr) and blood urea nitrogen (BUN) levels, and also attenuated the histopathological damage induced by I/R. Furthermore, TUNEL assay revealed that brazilin reduced cell necrosis, and significantly decreased the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in renal tissue. Moreover, HK-2 cells were used in order to elucidate the mechanisms responsible for the protective effects of brazilin. The levels of phosphorylated IκBα and the nuclear translocation of nuclear factor-κB (NF-κB) were all evidently decreased by brazilin. These findings suggested that pre-treatment with brazilin protects against I/R-induced renal damage and suppresses the inflammatory response by inhibiting the activation of the NF-κB signaling pathway. PMID:27247107

  17. Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia–reperfusion injury in rats

    PubMed Central

    Erer, Dilek; Özer, Abdullah; Demirtaş, Hüseyin; Gönül, İpek Işık; Kara, Halil; Arpacı, Hande; Çomu, Faruk Metin; Oktar, Gürsel Levent; Arslan, Mustafa; Küçük, Ayşegül

    2016-01-01

    Objectives To evaluate the effects of alprostadil (prostaglandin [PGE1] analog) and iloprost (prostacyclin [PGI2] analog) on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R) injury in an experimental rat model. Materials and methods Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius) tissue specimens were examined. Results Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (P<0.0001, P=0.015, and P<0.01, respectively). Polymorphonuclear leukocyte infiltration, pulmonary partial destruction, consolidation, alveolar edema, and hemorrhage scores were significantly lower in alprostadil- and iloprost-treated groups (P=0.017 and P=0.001; P<0.01 and P<0.0001). Polymorphonuclear leukocyte infiltration scores in skeletal muscle tissue were significantly lower in the iloprost-treated group than the scores found in the nontreated I/R group (P<0.0001). Conclusion Alprostadil and iloprost significantly reduce lung tissue I/R injury. Alprostadil has more prominent protective effects against renal I/R injury, while iloprost is superior in terms of protecting the skeletal muscle tissue against I/R injury. PMID:27601882

  18. Effects of Probenecid and Cimetidine on Renal Disposition of Ofloxacin in Rats

    PubMed Central

    Foote, Edward F.; Halstenson, Charles E.

    1998-01-01

    The renal handling of ofloxacin in rats which were given ofloxacin either alone or in combination with probenecid or cimetidine was studied. In the presence of cimetidine or probenecid, ofloxacin’s total and renal clearances were reduced and its half-life was prolonged. This suggests that ofloxacin is secreted by both the anionic and cationic transport systems. PMID:9527807

  19. EFFECTS OF CADMIUM ON RENAL AGING: A CHRONIC CADMIUM FEEDING STUDY IN RATS

    EPA Science Inventory

    Cadmium (Cd) is known to accumulate preferentially in the renal proximal tubules. Animal and human autopsy studies have shown that damage to the renal proximal tubular cells is associated with toxicity from chronic Cd exposure. The present study was undertaken to determine if Cd ...

  20. Protective effect of theophylline on renal functions in experimental pneumoperitoneum model.

    PubMed

    Ozturk, Sefa Alperen; Ceylan, Cavit; Serel, Tekin Ahmet; Doluoglu, Omer Gokhan; Soyupek, Arap Sedat; Guzel, Ahmet; Özorak, Alper; Uz, Efkan; Savas, Hasan Basri; Baspinar, Sirin

    2015-07-01

    Our objective in this experimental study is to research the effect of the intra-abdominal pressure which rises following pneumoperitoneum and whether Theophylline has a possible protective activity on this situation. In our study, 24 Wistar Albino rats were used. Rats were divided into two groups. The first group was set for only pneumoperitoneum model. The second group was given 15 mg/kg of Theophylline intraperitoneally before setting pneumoperitoneum model. Then urea, creatinine, cystatin-C, tissue and serum total antioxidant capacity, total oxidant capacity and oxidative stress index in two groups were measured and compared with each other. Apoptosis and histopathological conditions in the renal tissues were examined. The differences between the groups were analyzed with the Mann-Whitney U test. Results were considered significant at p < 0.05. No statistically significant difference was determined between tissue and serum averages in two groups in terms of TAS, TOS and OSI values (p > 0.05). The mean value of urea were similar in pneumoperitoneum and pneumoperitoneum + theophylline groups (p = 0.12). The mean cystatin-C value was 2.2 ± 0.3 µg/mL in pneumoperitoneum, 1.74 ± 0.33 µg/mL in pneumoperitoneum + theophylline (p = 0.002). According to our study, lower cystatin-C levels in the group, where Theophylline was given, are suggestive of lower renal injury in this group. However, this opinion is interrogated as there is no difference in terms of tissue and serum TAS, TOS, OSI and urea values between the groups. PMID:25959022

  1. Effects of hemodialysis on ventricular activation time in children with end-stage renal disease.

    PubMed

    Laszki-Szcząchor, Krystyna; Polak-Jonkisz, Dorota; Zwolińska, Danuta; Makulska, Irena; Rehan, Leopold; Sobieszczańska, Małgorzata

    2015-01-01

    Patients with end-stage renal disease are affected by cardiovascular complications, including disturbances of the heart intraventricular conduction. Body surface potential mapping is a non-invasive electrocardiographic detection method of initial disturbances in heart activation propagation. A goal of the study was to analyze the effects of single hemodialysis (HD) session on ventricular activation time (VAT) maps obtained from hemodialyzed children. The study group consisted of 13 hemodialyzed children (age: 6-18 years). The control group is composed of 26 healthy subjects. In each HD patient, 12-lead electrocardiogram and echocardiography examinations were performed. Isochrone heart maps, reflecting body surface distribution of VAT isolines, were recorded from an 87-electrode HPM-7100 system for body surface potential mapping, before (group B) and after HD session (group A). The distribution of isochrones and VAT values, as recorded in the HD patients, differed significantly from the reference VAT map for controls. The highest VAT maximal value was noted in group B (Me: 110 vs. 62 ms in the control group; P < 0.001), becoming significantly lower after HD session (Me: 98 ms for group A vs. 110 ms for group B; P < 0.001). Ventricular activation time maps, recorded before HD session, showed significant VAT delays with isochrone arrangement specific for the left bundle branch block. After HD session, VAT maps presented significant changes, suggesting a normalization process. Ventricular activation time maps in children with end-stage renal disease exhibited disturbances of intraventricular conduction within the left bundle branch block, undetectable on standard electrocardiogram. A single HD session resulted in VAT map improvement related to overall HD treatment duration. PMID:24992701

  2. Effect of birth weight on adulthood renal function: A bias-adjusted meta-analytic approach.

    PubMed

    Das, Sumon Kumar; Mannan, Munim; Faruque, Abu Syed Golam; Ahmed, Tahmeed; McIntyre, Harold David; Al Mamun, Abdullah

    2016-07-01

    While the association between low birth weight (LBW; <2500 g) and development of adult chronic renal disease (CKD) is inconsistently reported, less information is available regarding association of high birth weight (HBW; ≥4000 g) with CKD. We undertook a systematic review and meta-analysis on studies published before 30 September 2015 and report associations between birth weight and renal function. Blood (glomerular filtration rate (GFR)) and urine (microalbuminuria/albumin excreation rate (AER)/urinary albumin creatinine ratio (ACR)) parameters were used to define CKD. Three different effect size estimates were used (odds ratio, regression coefficient and mean difference). The odds of developing CKD in the life course among those born LBW was 1.77 (95% CI: 1.42, 2.20) times and 1.68 (1.27, 2.33) times, assessed by blood and urine parameters respectively. Higher risk was also observed among Asian and Australian populations (blood: OR 2.68; urine: OR 2.28), individuals aged ≤30 years (blood: OR 2.30; urine: OR 1.26), and ≥50 years (blood: OR 3.66; urine: OR 3.10), people with diabetes (blood: OR 2.51), and aborigines (urine: OR 2.32). There was no significant association between HBW and CKD. For every 1 kg increase in BW, the estimated GFR increased by 2.09 mL/min per 1.73 m(2) (1.33-2.85), and it was negatively associated with LogACR (ß -0.07, 95% CI: -0.14, 0.00). LBW inborn had lower mean GFR -4.62 (-7.10, -2.14) compared with normal BW. Findings of this study suggest that LBW increased the risk of developing CKD, and HBW did not show any significant impact. PMID:26807855

  3. Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes

    PubMed Central

    Mauer, Michael; Zinman, Bernard; Gardiner, Robert; Suissa, Samy; Sinaiko, Alan; Strand, Trudy; Drummond, Keith; Donnelly, Sandra; Goodyer, Paul; Gubler, Marie Claire; Klein, Ronald

    2010-01-01

    Background Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether early administration of drugs that block the renin-angiotensin system slows their progression. Methods The Renin Angiotensin System Study [RASS] was a multicenter controlled trial in 285 normoalbuminuric, normotensive type 1 diabetic patients who were randomized to losartan (100mg daily), enalapril (20mg daily) or placebo and followed for 5 years. The primary endpoint was change in glomerular mesangial fractional volume in kidney biopsies. The retinopathy endpoint was a 2-step or greater progression in retinopathy severity scale. Intention-to-treat data analyses used linear and logistic regression models. Results Ninety and 82% of patients had complete renal biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over 5 years in placebo (0.016 units) was not significantly different from enalapril (p=0.38) or losartan (p=0.26), nor were there significant changes in other biopsy assessed renal structural variables. Five-year cumulative microalbuminuria incidence was higher for losartan than placebo (14% vs. 4%; logrank p=0.015) but not for enalapril (6% vs. 4%; logrank p=0.96). Two-step or more retinopathy progression incidence was reduced by 65% in the enalapril (O.R. 0.35; 95% C.I., 0.14–0.85) and 70% in the losartan group (O.R. 0.30; 95% C.I., 0.12–0.73) independent of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 enalapril, 6 losartan and 4 placebo patients. Conclusions Early renin-angiotensin system blockade did not modify nephropathy progression in type 1 diabetic patients, but had important effects in slowing retinopathy. PMID:19571282

  4. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    SciTech Connect

    Wendler, J. J. Porsch, M.; Huehne, S.; Baumunk, D.; Buhtz, P.; Fischbach, F.; Pech, M.; Mahnkopf, D.; Kropf, S.; Roessner, A.; Ricke, J.; Schostak, M.; Liehr, U.-B.

    2013-04-15

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

  5. The Evolution of Institutional Effectiveness in the Community College

    ERIC Educational Resources Information Center

    Head, Ronald B.

    2011-01-01

    The origins of institutional effectiveness are traced, its evolution within community colleges is described, the use of the term "institutional effectiveness" is analyzed, and a practical, operational definition of the term is presented. The author hopes that this definition and the discussion in this article prove useful to community college…

  6. Effect of FTY720 (fingolimod) on graft survival in renal transplant recipients: a systematic review protocol

    PubMed Central

    Gholamnezhadjafari, Reza; Falak, Reza; Aflatoonian, Reza; Ali Keshtkar, Abbas; Rezaei, Abbas

    2016-01-01

    Introduction Studies have shown that FTY720 has inconsistent effects in kidney transplant recipients. Several review articles on FTY720 have been published, but most have focused on the mechanism of action of FTY720. Therefore, this review aims to evaluate and determine the beneficial and harmful effects of FTY720 therapy in kidney transplant recipients. Methods and analysis We electronically searched the following databases: PubMed, Scopus, the Web of Sciences, EMBASE, Cochrane databases and the Cochrane Central Registry of Controlled Trials. Any clinical, randomised controlled trials relating to FTY720 for treating kidney transplant recipients were included without publication status or language restriction. Study selection, data extraction and assessment of study quality were performed independently by two researchers. Data were synthesised by either the fixed effects or the random effects model according to a heterogeneity test. If the extracted data were suitable for meta-analysis, STATA software was used to combine the relative risks for dichotomous outcomes, and the mean differences for continuous outcomes with 95% CIs were measured. Death, loss of function and incidence of acute kidney rejection were assessed as the primary outcomes. Renal graft function, malignancy, delayed graft function and infection were evaluated as secondary outcomes. Ethics/dissemination This review does not require formal ethics approval because the data are not individualised. The resulting review article will be submitted for publication in a peer-reviewed journal. Trial registration number CRD42015024648. PMID:27126975

  7. Effects of lead on the renal response to extracellular volume expansion

    SciTech Connect

    Powers, W.J. Jr.; Foulkes, E.C.

    1985-01-01

    Subacute lead exposure has been observed to inhibit the natriuretic response to isotonic saline expansion in adult female rats. Three-week exposure to 0.5% lead acetate in drinking water resulted in a moderately high blood lead concentration of 57 ..mu..g/100 ml and up to 60% inhibition of the natriuretic response to extracellular volume expansion. This ability of lead to inhibit natriuresis following volume expansion (an induced stress) may be a more sensitive index of lead poisoning than alterations of renal function in nonstressed animals. Lead exposure had no effect on glomerular filtration rate (GFR) or plasma aldosterone concentrations, and in the presence of large doses of DOCA (a mineralocorticoid) this inhibitory effect of lead was still persistent. Amiloride completely blocked the antinatriuretic effect of lead in volume-expanded lead-poisoned animals, causing a twofold increase in water and electrolyte excretion while having minimal effects on volume-expanded controls. It is concluded that lead interferes with the action of a third factor, controlling natriuresis.

  8. Renal and Glycemic Effects of High-Dose Chromium Picolinate in db/db Mice: Assessment of DNA Damage

    PubMed Central

    Mozaffari, Mahmood S.; Baban, Babak; Abdelsayed, Rafik; Liu, Jun Yao; Wimborne, Hereward; Rodriguez, Nancy; Abebe, Worku

    2011-01-01

    This study examined renal and glycemic effects of chromium picolinate (Cr(pic)3) supplementation in the context of its purported potential for DNA damage. In preventional protocol, male obese diabetic db/db mice were fed diets either lacking or containing 5, 10 or 100 mg/kg chromium as Cr(pic)3 from 6 to 24 weeks of age; male lean nondiabetic db/m mice served as controls. Untreated db/db mice displayed increased plasma glucose and insulin, hemoglobin A1c, renal tissue advanced glycation end (AGE) products, albuminuria, glomerular mesangial expansion, urinary 8-hydroxydeoxyguanosine (8-OHdG, an index of oxidative DNA damage) and renal tissue immunostaining for γH2AX (a marker of double-strand DNA breaks) compared to db/m controls. Creatinine clearance was lower while blood pressure was similar between untreated db/db mice and their db/m controls. High Cr(pic)3 intake (i.e., 100 mg/kg diet) mildly improved glycemic status and albuminuria without affecting blood pressure or creatinine clearance. Treatment with Cr(pic)3 did not increase DNA damage despite marked renal accumulation of chromium. In interventional protocol, effects of diets containing 0, 100 and 250 mg/kg supplemental chromium, from 12 to 24 weeks of age, were examined in db/db mice. The results generally revealed similar effects to those of the 100 mg/kg diet of the preventional protocol. In conclusion, the severely hyperglycemic db/db mouse displays renal structural and functional abnormalities in association with DNA damage. High-dose Cr(pic)3 treatment mildly improves glycemic control and it causes moderate reduction in albuminuria, without affecting histopathological appearance of the kidney and increasing the risk for DNA damage. PMID:21959055

  9. Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease.

    PubMed

    Irazabal, Maria V; Torres, Vicente E; Hogan, Marie C; Glockner, James; King, Bernard F; Ofstie, Troy G; Krasa, Holly B; Ouyang, John; Czerwiec, Frank S

    2011-08-01

    Tolvaptan and related V(2)-specific vasopressin receptor antagonists have been shown to delay disease progression in animal models of polycystic kidney disease. Slight elevations in serum creatinine, rapidly reversible after drug cessation, have been found in clinical trials involving tolvaptan. Here, we sought to clarify the potential renal mechanisms to see whether the antagonist effects were dependent on underlying renal function in 20 patients with autosomal dominant polycystic kidney disease (ADPKD) before and after 1 week of daily split-dose treatment. Tolvaptan induced aquaresis (excretion of solute-free water) and a significant reduction in glomerular filtration rate (GFR). The serum uric acid increased because of a decreased uric acid clearance, and the serum potassium fell, but there was no significant change in renal blood flow as measured by para-aminohippurate clearance or magnetic resonance imaging (MRI). No correlation was found between baseline GFR, measured by iothalmate clearance, and percent change in GFR induced by tolvaptan. Blinded post hoc analysis of renal MRIs showed that tolvaptan significantly reduced total kidney volume by 3.1% and individual cyst volume by 1.6%. Preliminary analysis of this small cohort suggested that these effects were more noticeable in patients with preserved renal function and with larger cysts. No correlation was found between changes of total kidney volume and body weight or estimated body water. Thus, functional and structural effects of tolvaptan on patients with ADPKD are likely due to inhibition of V(2)-driven adenosine cyclic 3',5'-monophosphate generation and its aquaretic, hemodynamic, and anti-secretory actions. PMID:21544064

  10. Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban.

    PubMed

    Chang, Ming; Yu, Zhigang; Shenker, Andrew; Wang, Jessie; Pursley, Janice; Byon, Wonkyung; Boyd, Rebecca A; LaCreta, Frank; Frost, Charles E

    2016-05-01

    This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr ) as a measure of renal function. The relationships between 24-hour CLcr and iohexol clearance, estimated CLcr (Cockcroft-Gault equation), and estimated glomerular filtration rate (modification of diet in renal disease [MDRD] equation) were also assessed. Secondary objectives included assessment of safety and tolerability as well as international normalized ratio (INR) and anti-factor Xa activity as pharmacodynamic endpoints. The regression analysis showed that decreasing renal function resulted in modestly increased apixaban exposure (AUC∞ increased by 44% in severe impairment with a 24-hour CLcr of 15 mL/min, compared with subjects with normal renal function), but it did not affect Cmax or the direct relationship between apixaban plasma concentration and anti-factor Xa activity or INR. The assessment of renal function measured by iohexol clearance, Cockcroft-Gault, and MDRD was consistent with that determined by 24-hour CLcr . Apixaban was well tolerated in this study. These results suggest that dose adjustment of apixaban is not required on the basis of renal function alone. PMID:26358690

  11. Cost-effectiveness analysis of timely dialysis referral after renal transplant failure in Spain

    PubMed Central

    2012-01-01

    Background A cost-effectiveness analysis of timely dialysis referral after renal transplant failure was undertaken from the perspective of the Public Administration. The current Spanish situation, where all the patients undergoing graft function loss are referred back to dialysis in a late manner, was compared to an ideal scenario where all the patients are timely referred. Methods A Markov model was developed in which six health states were defined: hemodialysis, peritoneal dialysis, kidney transplantation, late referral hemodialysis, late referral peritoneal dialysis and death. The model carried out a simulation of the progression of renal disease for a hypothetical cohort of 1,000 patients aged 40, who were observed in a lifetime temporal horizon of 45 years. In depth sensitivity analyses were performed in order to ensure the robustness of the results obtained. Results Considering a discount rate of 3 %, timely referral showed an incremental cost of 211 €, compared to late referral. This cost increase was however a consequence of the incremental survival observed. The incremental effectiveness was 0.0087 quality-adjusted life years (QALY). When comparing both scenarios, an incremental cost-effectiveness ratio of 24,390 €/QALY was obtained, meaning that timely dialysis referral might be an efficient alternative if a willingness-to-pay threshold of 45,000 €/QALY is considered. This result proved to be independent of the proportion of late referral patients observed. The acceptance probability of timely referral was 61.90 %, while late referral was acceptable in 38.10 % of the simulations. If we however restrict the analysis to those situations not involving any loss of effectiveness, the acceptance probability of timely referral was 70.10 %, increasing twofold that of late referral (29.90 %). Conclusions Timely dialysis referral after graft function loss might be an efficient alternative in Spain, improving both patients’ survival rates and

  12. Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential

    PubMed Central

    Peters, Brandilyn A.; Liu, Xinhua; Hall, Megan N.; Ilievski, Vesna; Slavkovich, Vesna; Siddique, Abu B.; Alam, Shafiul; Islam, Tariqul; Graziano, Joseph H.; Gamble, Mary V.

    2015-01-01

    Exposure to arsenic (As) in drinking water is a widespread public health problem leading to increased risk for multiple outcomes such as cancer, cardiovascular disease, and possibly renal disease; potential mechanisms include inflammation and oxidative stress. We tested the hypothesis that As exposure is associated with increased inflammation and decreased estimated glomerular filtration rate (eGFR) and examined whether the effects of As were modified by plasma glutathione (GSH), glutathione disulfide (GSSG), or the reduction potential of the GSSG/2GSH pair (EhGSH). In a cross-sectional study of N = 374 Bangladeshi adults having a wide range of As exposure, we measured markers of inflammation (plasma C-reactive protein (CRP), α-1 acid glycoprotein (AGP)), renal function (eGFR), GSH, and GSSG. In covariate-adjusted models, a 10% increase in water As, urinary As adjusted for specific gravity (uAs), or blood As (bAs) was associated with a 0.74% (p = 0.01), 0.90% (p = 0.16), and 1.39% (p = 0.07) increase in CRP, respectively; there was no association with AGP. A 10% increase in uAs or bAs was associated with an average reduction in eGFR of 0.16 (p = 0.12) and 0.21 ml/min/1.73 m2 (p = 0.08), respectively. In stratified analyses, the effect of As exposure on CRP was observed only in participants having EhGSH > median (uAs pWald = 0.03; bAs pWald = 0.05). This was primarily driven by stronger effects of As exposure on CRP in participants with lower plasma GSH. The effects of As exposure on eGFR were not modified significantly by EhGSH, GSH, or GSSG. These data suggest that participants having lower plasma GSH and a more oxidized plasma EhGSH are at increased risk for As-induced inflammation. Future studies should evaluate whether antioxidant treatment lowers plasma EhGSH and reduces risk for As-induced diseases. PMID:25916185

  13. Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Ab Wahab, Mohd S.; Sirajudeen, Kuttulebbai N. S.; Salleh, Salzihan; Gurtu, Sunil

    2012-01-01

    Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR. PMID:22315654

  14. Effects of morphine on the renal handling of sodium and lithium in conscious rats.

    PubMed

    el-Awady, E S; Walker, L A

    1990-09-01

    The present study was carried out in order to assess the renal response to i.v. morphine in the rat, particularly the effects on tubular handling of sodium and lithium. Rats were prepared surgically with arterial and venous catheters and bladder cannulas. Clearance experiments and measurements of blood pressure and heart rate were carried out at least 4 days after surgery in unanesthetized animals. Intravenous administration of morphine (4 mg/kg b.wt.) caused a decrease in fractional sodium excretion, (at 90 min after injection, vehicle, 2.49 +/- 0.30% vs. morphine, 1.12 +/- 0.17%, P less than .05), in the absence of significant changes in systemic hemodynamics or glomerular filtration rate. This effect was prevented by pretreatment with naloxone. Enhanced proximal tubular reabsorption of sodium was considered as a possible explanation for the decrease in sodium excretion which followed morphine administration. Proximal tubular fluid reabsorption was estimated utilizing the lithium clearance method. Results indicated a reduction in fractional excretion of lithium by morphine administration (at 90 min, vehicle, 34.2 +/- 3.3% vs. morphine, 18.8 +/- 2.3%, P less than .05), which was also prevented by naloxone pretreatment. It is concluded that, under the present experimental conditions, morphine enhances tubular reabsorption of sodium by an opiate receptor-dependent mechanism and that this effect is, at least in part, localized in the proximal tubule. PMID:2395123

  15. Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress.

    PubMed

    Erejuwa, Omotayo O; Sulaiman, Siti A; Ab Wahab, Mohd S; Sirajudeen, Kuttulebbai N S; Salleh, Salzihan; Gurtu, Sunil

    2012-01-01

    Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR. PMID:22315654

  16. The effects of continuous and intermittent reduced speed modes on renal and intestinal perfusion in an ovine model.

    PubMed

    Tuzun, Egemen; Chorpenning, Katherine; Liu, Maxine Qun; Bonugli, Katherine; Tamez, Dan; Lenox, Mark; Miller, Matthew W; Fossum, Theresa W

    2014-01-01

    The effects of the continuous-flow output on renal and intestinal microcirculation have not been extensively studied. To address this, the Heartware HVAD pump loaded with continuous and intermittent reduced speed (IRS) modes was implanted in four sheep and then operated at low and high speeds to mimic partial and complete unloading of the left ventricle. Then microsphere and positron emission tomography/computed tomography (PET/CT) studies were used to assess renal and intestinal tissue perfusion at various pump speeds and flow modes as compared with baseline (pump off). Arterial and venous oxygen (T02) and carbon dioxide (TCO2) contents were measured to assess changes in intestinal metabolism. Renal and intestinal regional blood flows did not produce any significant changes compared with baseline values in either continuous or IRS modes and speeds. The venous TO2 and TCO2 significantly increased in continuous and IRS modes and speeds compared with baseline. Our data suggested that renal and intestinal tissue perfusions were not adversely affected by continuous and IRS modes either in partial or complete unloading. Intestinal venous hyperoxia and increased TCO2 may be the evidence of intestinal arteriovenous shunting along with increased intestinal tissue metabolism. Longer-term studies are warranted in chronic heart failure models. PMID:24299973

  17. Renoprotective effect of berberine via intonation on apoptosis and mitochondrial-dependent pathway in renal ischemia reperfusion-induced mutilation.

    PubMed

    Visnagri, Asjad; Kandhare, Amit D; Bodhankar, Subhash L

    2015-04-01

    Ischemic acute renal failure is a condition that extends subsequent to sudden and momentary fall in overall or regional blood flow to the kidney. The present investigation was deliberated to scrutinize the renoprotective potential of berberine in animal model of renal ischemia reperfusion (RIR) induced dent via assessment of various biochemical and molecular biomarkers. Male Wistar rats were anesthetized and the right kidney was removed through a small flank incision. Renal ischemia reperfusion was persuaded in uni-nephrectomized rats by occlusion of left renal artery for 45 min and reperfusion for 4 weeks. After 4 weeks of treatment of berberine (10, 20, and 40 mg/kg, p.o.), hemodynamic and left ventricular function were evaluated. Induction of ischemia reperfusion resulted callous mutilation in kidney which was confirmed by alterations in oxidative stress (SOD, GSH, and MDA), membrane bound enzymes, kidney function markers (serum creatinine and BUN), and mitochondrial dysfunction. Moreover, RIR injury exhibited incredible alterations in mRNA expression of KIM-1, NGAL, Caspase-3, Bax, Bcl-2, and TNF-α levels. Conversely treatment of berberine (20 and 40 mg/kg) significantly (p < 0.01 and p < 0.001) restored ischemia reperfusion induced marring via intonation of biochemical and molecular biomarkers. To sum up, berberine demonstrated compelling renoprotective effect in RIR injury via caspase-mitochondria-dependent pathway. PMID:25598236

  18. The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles.

    PubMed

    Ali, Badreldin H; Al Za'abi, Mohammed; Shalaby, Asem; Manoj, Priyadarsini; Waly, Mostafa I; Yasin, Javed; Fahim, Mohamed; Nemmar, Abderrahim

    2015-12-01

    Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP. PMID:25925792

  19. Alleviative effect of myricetin on ochratoxin A-induced oxidative stress in rat renal cortex: histological and biochemical study.

    PubMed

    El-Haleem, Manal R Abdel; Kattaia, Asmaa A A; El-Baset, Samia A Abdel; Mostafa, Heba El Sayed

    2016-04-01

    Ochratoxins (OTA) are secondary metabolites of Aspergillus and Penicillium. The detoxification of OTA has been of major interest due to its widespread threat to human health. We aimed to investigate the possible alleviative effect of myricetin (MYR) against OTA-induced damage in renal cortex of rats. Thirty adult male albino rats were randomized into five equal groups: control (untreated), vehicle control (0.5 ml corn oil/day including dimethylsulfoxide [DMSO]), MYR (100 mg MYR/kg b.w./day in distilled water), OTA (0.5 mg OTA/kg b.w./day; dissolved in 10% DMSO and then corn oil) and OTA + MYR group (received OTA and MYR at similar doses). All treatments were given by oral gavage for 2 weeks. At the end of the experiment, renal cortices were processed for light and electron microscope examinations. Immunohistochemical staining for localization of proliferating cell nuclear antigen (PCNA), p53 and transforming growth factor beta 1 (TGF-β1) was carried out. Biochemical analysis of tissue glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress. OTA administration induced deleterious renal injury evidenced by the structural and ultra-structural changes. Immunohistochemical expression of p53, PCNA and TGF-β1 were significantly up regulated compared with control. Alterations in antioxidant parameters supported that oxidative stress was one of the mechanisms involved in OTA toxicity. On the contrary, co-administration of MRY partially ameliorated OTA-induced renal injury. We suggest the potential effectiveness of MYR to counteract OTA-induced toxic oxidative stress on the renal cortex. PMID:26571153

  20. The Evolution of Soft Collinear Effective Theory

    DOE PAGESBeta

    Lee, Christopher

    2015-02-25

    Soft Collinear Effective Theory (SCET) is an effective field theory of Quantum Chromodynamics (QCD) for processes where there are energetic, nearly lightlike degrees of freedom interacting with one another via soft radiation. SCET has found many applications in high-energy and nuclear physics, especially in recent years the physics of hadronic jets in e+e-, lepton-hadron, hadron-hadron, and heavy-ion collisions. SCET can be used to factorize multi-scale cross sections in these processes into single-scale hard, collinear, and soft functions, and to evolve these through the renormalization group to resum large logarithms of ratios of the scales that appear in the QCD perturbativemore » expansion, as well as to study properties of nonperturbative effects. We overview the elementary concepts of SCET and describe how they can be applied in high-energy and nuclear physics.« less

  1. The Evolution of Soft Collinear Effective Theory

    SciTech Connect

    Lee, Christopher

    2015-02-25

    Soft Collinear Effective Theory (SCET) is an effective field theory of Quantum Chromodynamics (QCD) for processes where there are energetic, nearly lightlike degrees of freedom interacting with one another via soft radiation. SCET has found many applications in high-energy and nuclear physics, especially in recent years the physics of hadronic jets in e+e-, lepton-hadron, hadron-hadron, and heavy-ion collisions. SCET can be used to factorize multi-scale cross sections in these processes into single-scale hard, collinear, and soft functions, and to evolve these through the renormalization group to resum large logarithms of ratios of the scales that appear in the QCD perturbative expansion, as well as to study properties of nonperturbative effects. We overview the elementary concepts of SCET and describe how they can be applied in high-energy and nuclear physics.

  2. Action of anti-bothropic factor isolated from Didelphis marsupialis on renal effects of Bothrops erythromelas venom.

    PubMed

    Martins, Alice M C; Sousa, Fabiola C M; Barbosa, Paulo S F; Toyama, Marcos H; Toyama, Daniela O; Aprígio, Cleidiana C; Queiroz, Maria G R; Guarnieri, Mirian C; Havt, Alexandre; de Menezes, Dalgimar B; Fonteles, Manassés C; Monteiro, Helena S A

    2005-11-01

    Acute renal failure is the most common complication in the lethal cases caused by snakebites in Brazil. Among the Brazilian venom snakes, Bothrops erythromelas is responsible for the majority of accidents in Northeastern Brazil. Didelphis marsupialis serum could inhibit myonecrotic, hemorrhagic, edematogenic hyperalgesic and lethal effects of envenomation determined by ophidian bites. In the present study, we evaluated the action of the anti-bothropic factor isolated from D. marsupialis on the renal effects promoted by B. erythromelas venom without systemic interference. Isolated kidneys from Wistar rats were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. We analyzed renal perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), and the percentages of sodium and potassium tubular transport (%TNa+, %TK+). The B. erythromelas venom (10 microg mL(-1)) decreased the PP (ct = 108.71+/-5.09 mmHg; BE = 65.21+/-5.6 mmHg*) and RVR (ct = 5.76+/-0.65 mmHg mL(-1) g(-1) min(-1); BE = 3.10+/-0.45 mmHg mL(-1) g(-1) min(-1)*). On the other hand, the GFR decreased at 60 min (ct60 = 0.76+/-0.07 mL g(-1) min(-1); BE60 = 0.42+/-0.12 mL g(-1) min(-1)*) and increased at 120 min (ct120 = 0.72+/-0.01 mL g(-1) min(-1); BE120 = 1.24+/-0.26 mL g(-1) min(-1)*). The UF increased significantly when compared with the control group (ct = 0.14+/-0.01 mL g(-1) min(-1); BE = 0.47+/-0.08 mL g(-1) min(-1)*). The venom reduced the %TNa(+) (ct90 = 79.18+/-0.88%; BE90 = 58.35+/-4.86%*) and %TK+ (ct90 = 67.20+/-4.04%; BE90 = 57.32+/-5.26%*) The anti-bothropic factor from D. marsupialis (10 microg mL(-1)) incubated with B. erythromelas venom (10 microg mL(-1)) blocked the effects on PP, RVR, %TNa+, and %TK+, but was not able to reverse the effects in UF and GFR promoted by venom alone. However, the highest concentration of D. marsupialis serum (30 microg mL(-1)) reversed all the renal effects induced by the venom. In

  3. Cost-effectiveness of pazopanib compared with sunitinib in metastatic renal cell carcinoma in Canada

    PubMed Central

    Amdahl, J.; Diaz, J.; Park, J.; Nakhaipour, H.R.; Delea, T.E.

    2016-01-01

    Background In Canada and elsewhere, pazopanib and sunitinib—tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors—are recommended as first-line treatment for patients with metastatic renal cell carcinoma (mrcc). A large randomized noninferiority trial of pazopanib versus sunitinib (comparz) demonstrated that the two drugs have similar efficacy; however, patients randomized to pazopanib experienced better health-related quality of life (hrqol) and nominally lower rates of non-study medical resource utilization. Methods The cost-effectiveness of pazopanib compared with sunitinib for first-line treatment of mrcc from a Canadian health care system perspective was evaluated using a partitioned-survival model that incorporated data from comparz and other secondary sources. The time horizon of 5 years was based on the maximum duration of follow-up in the final analysis of overall survival from the comparz trial. Analyses were conducted first using list prices for pazopanib and sunitinib and then by assuming that the prices of sunitinib and pazopanib would be equivalent. Results Based on list prices, expected costs were CA$10,293 less with pazopanib than with sunitinib. Pazopanib was estimated to yield 0.059 more quality-adjusted life-years (qalys). Pazopanib was therefore dominant (more qalys and lower costs) compared with sunitinib in the base case. In probabilistic sensitivity analyses, pazopanib was dominant in 79% of simulations and was cost-effective in 90%–100% of simulations at a threshold cost-effectiveness ratio of CA$100,000. Assuming equivalent pricing, pazopanib yielded CA$917 in savings in the base case, was dominant in 36% of probabilistic sensitivity analysis simulations, and was cost-effective in 89% of simulations at a threshold cost-effectiveness ratio of CA$100,000. Conclusions Compared with sunitinib, pazopanib is likely to be a cost-effective option for first-line treatment of mrcc from a Canadian health care

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

    PubMed Central

    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 for 9 days. Groups 3, 4 and 5 received saline, PFE 25 mg/kg, and PFE 50 mg/kg for 9 days, respectively, and GM (100 mg/kg/day) was administered from day 3 on. Blood samples were obtained, and after sacrificing the animals, the kidneys were removed for histopathology investigations. Results: GM alone increased the serum levels of creatinine (Cr) and blood urea nitrogen (BUN), and tissue damage and kidney weight (P < 0.05). However, administration of low dose of PFE accompanied with GM decreased these markers significantly (P < 0.05). Low dose of PFE also ameliorated weight loss induced by GM (P < 0.05). Conclusion: It is concluded that PFE 25 mg/kg is the effective dose to ameliorate nephrotoxicity induced by GM. PMID:26060837

  5. Cost-Effectiveness of Pazopanib Versus Sunitinib for Renal Cancer in the United States.

    PubMed

    Benedict, Agnes; Ramaswamy, Krishnan; Sandin, Rickard

    2015-09-01

    We write to comment on a recently published study by Delea et al. in the January 2015 issue of JMCP that evaluated the cost-effectiveness (CE) of sunitinib (SU) versus pazopanib (PAZ) as first-line treatment for metastatic renal cell carcinoma (mRCC) from a U.S. third-party payer perspective.1 This analysis was based on COMPARZ and PISCES, clinical trials that compared SU and PAZ2,3 and led the authors to conclude that PAZ is cost-effective (in fact, dominant, according to the base-case results) compared with SU. Such assessment of economic value is clearly important for deciding between therapies to ensure fair access; therefore, we welcome a comparative evaluation of SU and PAZ. However, we believe that some of the key assumptions and inputs used in the model by Delea et al. render their results and conclusions invalid.  Best practice requires that results from a health economic model should reflect the most likely outcomes based on sound methodology and robust evidence for its inputs, as recommended by the International Society of Pharmacoeconomics and Outcomes Research (ISPOR).4 Here, we focus on 2 key areas (utilities and survival modeling) where, in our view, the analysis by Delea et al. falls short of this standard, and a third area (treatment costs) where the basis for the data derived is unclear. PMID:26308230

  6. Effect of vitamin C on endothelial function of children with chronic renal failure: An experimental study

    PubMed Central

    Sabri, Mohammad Reza; Tavana, Esfandiar Najafi; Ahmadi, Alireza; Gheissari, Alaleh

    2015-01-01

    Background: It is well established that improvement of endothelial dysfunction (ED) could prevent or delay the occurrence of cardiovascular disease (CVD) and its related morbidity and mortality in patients with chronic kidney disease (CKD). In this study we investigated whether administration of vitamin C could be effective by improving brachial artery flow-mediated dilation (FMD) and intima media thickness (IMT), two surrogate markers of ED, in children with CKD or chronic renal failure (CRF). Materials and Methods: In this analytic-experimental study children aged 3-18 years with a diagnosis of CRF and a group of healthy children were enrolled. Vitamin C (250 mg/day) administrated for the two studied groups for 1 month. Endothelial function was evaluated by FMD and IMT measurement using vascular Doppler ultrasonography, before and after trial. Results: In this study 18 patients with CRF and 19 normal children as the control group were studied. At baseline mean of IMT and FMD was not different in the two studied groups (P > 0.05). After vitamin C administration IMT decreased significantly in the two studied groups (P < 0.05). FMD increased in the two studied groups but the difference was significant in the control group (P < 0.05). Conclusion: The findings of this interventional trial have demonstrated that vitamin C could have protective effect on ED of patients with CRF possibly in those with severe form of the disease but for obtaining more conclusive results larger sample size is needed. PMID:26918242

  7. Nephroprotective effect of astaxanthin against trivalent inorganic arsenic-induced renal injury in wistar rats

    PubMed Central

    Wang, Xiaona; Zhao, Haiyuan; Shao, Yilan; Wang, Pei; Wei, Yanru; Zhang, Weiqian; Jiang, Jing; Chen, Yan

    2014-01-01

    Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide (As2O3) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As (iAsIII) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by As2O3 exposure (via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, Na+-K+ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of As2O3 exposure. AST showed a significant protective effect against As2O3-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to iAsIII from natural sources or cancer therapy. PMID:24611105

  8. Effects of Hoe 140, a bradykinin B2-receptor antagonist, on renal function in conscious normotensive rats.

    PubMed Central

    Madeddu, P.; Anania, V.; Parpaglia, P. P.; Demontis, M. P.; Varoni, M. V.; Pisanu, G.; Troffa, C.; Tonolo, G.; Glorioso, N.

    1992-01-01

    1. The present study was designed to determine if endogenous kinins are involved in the regulation of arterial blood pressure and renal function in conscious rats given deoxycorticosterone enantate (DOC, 25 mg kg-1, s.c., weekly) or vehicle for two weeks. 2. The bradykinin B2-receptor antagonist, D-Arg[Hyp3,Thi5,D-Tic7,Oic8]- bradykinin (Hoe 140), at a dose of 300 micrograms kg-1, s.c., blocked the hypotensive effect of 300 ng kg-1 bradykinin i.a., but it did not alter the blood pressure lowering action of 300 ng kg-1 acetylcholine or prostaglandin E2. Inhibition of the response to bradykinin persisted up to 6 h after the administration of Hoe 140. 3. Administration of 300 micrograms kg-1 Hoe 140 s.c. four times a day did not alter mean blood pressure, renal blood flow, or renal function in rats given DOC-vehicle. However, it decreased urinary volume by 70% (from 48.2 +/- 3.8 to 14.3 +/- 3.7 ml 24 h-1, P less than 0.01) and urinary secretion of sodium by 54% (from 1.02 +/- 0.05 to 0.47 +/- 0.16 mmol 24 h-1, P less than 0.01) and potassium by 30% (from 2.93 +/- 0.15 to 2.04 +/- 0.15 mmol 24 h-1, P less than 0.05) in DOC-treated rats. Mean blood pressure, glomerular filtration rate and total renal blood flow remained unchanged. 4. Our results suggest that endogenous kinins play a role in the regulation of renal excretion of water and sodium in the presence of elevated levels of DOC. PMID:1327379

  9. Effect of Helicobacter pylori infection on intragastric urea and ammonium concentrations in patients with chronic renal failure.

    PubMed Central

    Neithercut, W D; Rowe, P A; el Nujumi, A M; Dahill, S; McColl, K E

    1993-01-01

    AIM--To assess the value of measuring the gastric juice urea:ammonium ratio in detecting Helicobacter pylori infection in patients with chronic renal failure. METHODS--Twenty three (12 men) patients with established chronic renal failure and dyspepsia were studied. Gastric juice (2 ml) was aspirated during endoscopy to measure urea and ammonium. The upper gastrointestinal tract was routinely inspected and two antral biopsy specimens obtained. The 14C-urea breath test was conducted within 14 days of endoscopic examination to determine H pylori antibody response. RESULTS--The median (range) serum urea concentration in 11 patients with renal failure and H pylori infection was similar to that in 12 without H pylori infection. The median gastric juice urea concentration in subjects with infection was lower than that in the subjects without infection (p < 0.01). The median gastric juice ammonium concentration in subjects with the infection was higher compared with subjects without infection (p < 0.01). There was an overlap of the urea and ammonium concentrations in gastric juice from both H pylori positive and negative subjects. The urea:ammonium ratio was 0.16 (0.01-1.11) for subjects with H pylori compared with 1.63 (1.0-18.9) in subjects without infection (p < 0.001). CONCLUSION--The urea:ammonium ratio differentiated both groups, with the exception of one false negative result. The urea:ammonium ratio proved almost as effective in identifying the presence of H pylori infection in subjects with chronic renal failure as it had in subjects with normal renal function. PMID:8331178

  10. Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat.

    PubMed

    Chtourou, Yassine; Aouey, Baktha; Aroui, Sonia; Kebieche, Mohammed; Fetoui, Hamadi

    2016-01-01

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. Naringin, a natural flavonoid, plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the involvement of ROS overproduction and inflammation in cisplatin-induced nephrotoxicity in aged rats, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after treatment with naringin (20, 50 or 100 mg/kg body weight). Cisplatin resulted in an increase of renal markers, lipid peroxidation, protein and DNA oxidation, and ROS formation. Renal tumor necrosis factor-α (TNF-α) and nitrite levels were also elevated. Expressions of nuclear factor-kappa B (NF-κB), inductible nitric oxide synthase (iNOS), caspase-3 and p53 were up-regulated in renal tissues of Cis-treated rats compared with the normal control group. Histopathological changes were also observed in cisplatin group. Adminstration of naringin at different doses (25, 50 and 100 mg/kg) was able to protect against the deterioration in kidney function, abrogate the decline in antioxidant enzyme activities and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, naringin inhibited NF-κB and iNOS pathways, caspase-3 and p53 activation and improved the histological changes induced by cisplatin. In conclusion, our studies suggest that oxidative stress and inflammation might play important roles in the development of cisplatin-induced nephrotoxicity and naringin might become an effective therapeutic strategy for this disease. PMID:26612654

  11. The effect of renal and hepatic impairment on the pharmacokinetics of ospemifene, a tissue-selective estrogen agonist/antagonist.

    PubMed

    Preston, Richard A; Marbury, Thomas C; Wajima, Toshihiro; Graham, Shelli

    2015-01-01

    Ospemifene is a nonestrogen tissue-selective estrogen agonist/antagonist approved to treat moderate to severe dyspareunia due to vulvar and vaginal atrophy in postmenopausal women. Three single-dose, open-label, parallel-group pharmacokinetic studies examined the pharmacokinetics of ospemifene in postmenopausal women with (1) mild hepatic impairment (n = 7), (2) moderate hepatic impairment (n = 8), and (3) severe renal impairment (n = 8) compared with a similar number of matched healthy controls. The study durations ranged from 8 to 12 days. Study participants received a single oral dose of ospemifene 60 mg on day 1 and blood samples were collected serially. The geometric mean ratios (hepatic or renal impairment/healthy) and 90% confidence intervals (CIs) for area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) and maximum concentration (Cmax), respectively, of ospemifene were 90.86% (90% CI, 65.95%-125.19%) and 79.48% (90% CI, 65.95%-95.79%) in the mild hepatic impairment study; 128.62% (90% CI, 87.13%-189.88%) and 101.12% (90% CI, 66.17%-154.52%) in the moderate hepatic impairment study, and 119.63% (90% CI, 81.37%-175.88%) and 79.30% (90% CI, 52.85%-118.99%) in the severe renal impairment study. Overall, there was no clinically important effect of hepatic or renal impairment on the pharmacokinetics of ospemifene, indicating that dosing does not need to be adjusted in postmenopausal women with mild or moderate hepatic impairment or in subjects with severe renal impairment. PMID:24413373

  12. CS-3150, a Novel Nonsteroidal Mineralocorticoid Receptor Antagonist, Shows Preventive and Therapeutic Effects On Renal Injury in Deoxycorticosterone Acetate/Salt-Induced Hypertensive Rats.

    PubMed

    Arai, Kiyoshi; Morikawa, Yuka; Ubukata, Naoko; Tsuruoka, Hiroyuki; Homma, Tsuyoshi

    2016-09-01

    The present study was designed to assess both preventive and therapeutic effects of (S)-1-(2-Hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl) phenyl]-5-[2-(trifluoromethyl) phenyl]-1H-pyrrole-3-carboxamide (CS-3150), a novel nonsteroidal mineralocorticoid receptor antagonist, on renal injury in deoxycorticosterone acetate (DOCA)/salt-induced hypertensive rats (DOCA rats). From 7 weeks of age, DOCA was subcutaneously administered once a week for 4 weeks to uninephrectomized rats fed a high-salt diet. In experiment 1, CS-3150 (0.3-3 mg/kg) was orally administered once a day for 4 weeks coincident with DOCA administration. In experiment 2, after establishment of renal injury by 4 weeks of DOCA/salt loading, CS-3150 (3 mg/kg) was orally administered once a day for 4 weeks with or without continuous DOCA administration. In experiment 1, DOCA/salt loading significantly increased systolic blood pressure (SBP), which was prevented by CS-3150 in a dose-dependent manner. Development of renal injury (proteinuria, renal hypertrophy, and histopathological changes in glomeruli and tubule) was also suppressed by CS-3150 with inhibition of mRNA expression of fibrosis, inflammation, and oxidative stress markers. In experiment 2, under continuous DOCA treatment, CS-3150 clearly ameliorated existing renal injury without lowering SBP, indicating that CS-3150 regressed renal injury independent of its antihypertensive action. Moreover, CS-3150 treatment in combination with withdrawal of DOCA showed further therapeutic effect on renal injury accompanied by reduction in SBP. These results demonstrate that CS-3150 not only prevents but also ameliorates hypertension and renal injury in DOCA rats. Therefore, CS-3150 could be a promising agent for the treatment of hypertension and renal disorders, and may have potential to promote regression of renal injury. PMID:27384074

  13. Pseudomonas Exotoxin A: optimized by evolution for effective killing

    PubMed Central

    Michalska, Marta; Wolf, Philipp

    2015-01-01

    Pseudomonas Exotoxin A (PE) is the most toxic virulence factor of the pathogenic bacterium Pseudomonas aeruginosa. This review describes current knowledge about the intoxication pathways of PE. Moreover, PE represents a remarkable example for pathoadaptive evolution, how bacterial molecules have been structurally and functionally optimized under evolutionary pressure to effectively impair and kill their host cells. PMID:26441897

  14. Effect of pentoxifylline on renal outcomes in chronic kidney disease patients: A systematic review and meta-analysis.

    PubMed

    Leporini, Christian; Pisano, Anna; Russo, Emilio; D'Arrigo, Graziella; de Sarro, Giovambattista; Coppolino, Giuseppe; Bolignano, Davide

    2016-05-01

    Chronic kidney disease (CKD) represents an important health problem worldwide and the search for new therapeutic approaches for retarding CKD progression is a timely issue. Recent evidence suggest that the anti-inflammatory and hemorrheologic drug Pentoxifylline (PTX), may produce favorable effects on kidney function. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to ascertain whether PTX derivatives, alone or in combination to other treatments, may be useful in slowing down disease progression in patients with diabetic or non-diabetic CKD. We found 26 studies (1518 subjects) matching our search criteria. Information on the effects of PTX on hard renal outcomes (doubling of serum creatinine or need for chronic dialysis) were lacking in all the reviewed trials. Conversely, PTX was effective in reducing proteinuria compared to control, a benefit that was more evident in patients with type-1 diabetes mellitus, higher proteinuria at baseline and early renal impairment. An improvement in renal function (eGFR/creatinine clearance) was observed particularly in patients with more advanced CKD stage and in studies with longer follow-up. Conversely, cumulative analyses did not reveal any evident reduction in urinary albumin excretion, even in diabetic patients. The use of PTX was relatively safe as most trials recorded only minor gastrointestinal adverse effects. Although these findings point at some reno-protective effects of PTX, there is no conclusive evidence proving the usefulness of this agent for improving renal outcomes in subjects with chronic kidney disease of various etiology. Future trials adequately powered and designed on hard clinical end-points are needed. PMID:26995301

  15. Effects of Fluid Flow on Slip Evolution in a Thermoporoelastic Medium: Implications for Seismic Moment Evolution

    NASA Astrophysics Data System (ADS)

    Suzuki, T.; Yamashita, T.

    2015-12-01

    We have constructed a framework associated with the interaction among heat, fluid pressure and inelastic pore creation, and found three nondimensional parameters, Su, Su' and Ta, which are related to the dilatancy effect, fluid flow effect and the upper limit of the dilatancy, respectively. Without fluid flow, they were found to generate two qualitatively different slip behaviors, acceleration case and spontaneous slip cessation case. In particular, the acceleration case shows the initial deceleration and later acceleration approaching the final high-speed slip. Between the deceleration and acceleration phases, we observe a transient state featured by low and approximately constant slip velocity. We employ the fluid flow effect here and give some implications for understanding the temporal evolution of seismic moments. For example, Ide et al. (2007) found that ordinary earthquakes and slow earthquakes have different forms of temporal evolutions of the seismic moments. In addition, Duputel et al. (2013) observed examples showing exceptional moment evolution behavior even among ordinary earthquakes. Yamashita and Suzuki (2011) successfully modeled the former result by introducing slip-induced dilatancy coupled with fluid flow, while the modeling of the latter remains unaccomplished. If we introduce the fluid flow, we observe only the acceleration case and the duration of the transient state is longer than that without the fluid flow. This can be a model for a slow earthquake if we assume a 2-D model, and the seismic moment of such an earthquake evolves in almost a quadratic function in time. On the other hand, for the acceleration case without the fluid flow, the seismic moment evolution is almost a cubic function. Moreover, for the spontaneous slip cessation case, it evolves with a quadratic or linear function. The framework explaining all the behaviors mentioned above has been obtained. Quantitative investigation on the nondimensional parameters will also be done.

  16. Effects of Conformism on the Cultural Evolution of Social Behaviour

    PubMed Central

    Molleman, Lucas; Pen, Ido; Weissing, Franz J.

    2013-01-01

    Models of cultural evolution study how the distribution of cultural traits changes over time. The dynamics of cultural evolution strongly depends on the way these traits are transmitted between individuals by social learning. Two prominent forms of social learning are payoff-based learning (imitating others that have higher payoffs) and conformist learning (imitating locally common behaviours). How payoff-based and conformist learning affect the cultural evolution of cooperation is currently a matter of lively debate, but few studies systematically analyse the interplay of these forms of social learning. Here we perform such a study by investigating how the interaction of payoff-based and conformist learning affects the outcome of cultural evolution in three social contexts. First, we develop a simple argument that provides insights into how the outcome of cultural evolution will change when more and more conformist learning is added to payoff-based learning. In a social dilemma (e.g. a Prisoner’s Dilemma), conformism can turn cooperation into a stable equilibrium; in an evasion game (e.g. a Hawk-Dove game or a Snowdrift game) conformism tends to destabilize the polymorphic equilibrium; and in a coordination game (e.g. a Stag Hunt game), conformism changes the basin of attraction of the two equilibria. Second, we analyse a stochastic event-based model, revealing that conformism increases the speed of cultural evolution towards pure equilibria. Individual-based simulations as well as the analysis of the diffusion approximation of the stochastic model by and large confirm our findings. Third, we investigate the effect of an increasing degree of conformism on cultural group selection in a group-structured population. We conclude that, in contrast to statements in the literature, conformism hinders rather than promotes the evolution of cooperation. PMID:23874528

  17. Precedence effects and the evolution of chorusing

    PubMed Central

    Greenfield, M. D.; Tourtellot, M. K.; Snedden, W. A.

    1997-01-01

    The structured choruses produced by rhythmically signalling males in many species of acoustic animals have long-captured the imagination of evolutionary biologists. Though various hypotheses have been forwarded to explain the adaptive significance of such chorusing, none have withstood empirical scrutiny. We suggest instead that alternating and synchronous choruses represent collective epiphenomena resulting from individual males competing to jam each other's signals. These competitions originate in psychoacoustic precedence effects wherein females only orient toward the first call of a sequence, thus selectively favouring males who produce leading calls. Given this perceptual bias, our modelling confirms that a resetting of signal rhythm by neighbours' signals, which generates either alternation or synchrony, is evolutionarily stable provided that resetting includes a relativity adjustment for the velocity of signal transmission and selective attention toward only a subset of signalling neighbours. Signalling strategies in chorusing insects and anurans are consistent with these predicted features.

  18. [Atherosclerotic renal artery stenosis].

    PubMed

    Sauguet, A; Honton, B

    2014-12-01

    Atherosclerotic renal artery stenosis can cause ischaemic nephropathy and arterial hypertension. Renal artery stenosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Many patients with RAS may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the cardiovascular outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of RAS for cardiologists in the context of recent randomized clinical trials. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary edema, rapidly declining renal function and severe resistant hypertension. PMID:25450992

  19. Glucagon-like peptide-1 does not have acute effects on central or renal hemodynamics in patients with type 2 diabetes without nephropathy.

    PubMed

    Asmar, Ali; Simonsen, Lene; Asmar, Meena; Madsbad, Sten; Holst, Jens J; Frandsen, Erik; Moro, Cedric; Sorensen, Charlotte M; Jonassen, Thomas; Bülow, Jens

    2016-05-01

    During acute administration of native glucagon-like peptide-1 (GLP-1), we previously demonstrated central hemodynamic effects in healthy males, whereas renal hemodynamics, despite renal uptake of GLP-1 in excess of glomerular filtration, was unaffected. In the present study, we studied hemodynamic effects of GLP-1 in patients with type 2 diabetes under fixed sodium intake. During a 3-h infusion of GLP-1 (1.5 pmol·kg(-1)·min(-1)) or saline, intra-arterial blood pressure and heart rate were measured continuously, concomitantly with cardiac output estimated by pulse contour analysis. Renal plasma flow, glomerular filtration rate, and uptake/release of hormones and ions were measured using Fick's Principle after catheterization of a renal vein. Urine collection was conducted throughout the experiments at voluntary voiding, and patients remained supine during the experiments. During the GLP-1 infusion, systolic and diastolic blood pressure and cardiac output remained unchanged, whereas heart rate increased significantly. Arterio-venous gradients for GLP-1 exceeded glomerular filtrations significantly, but renal plasma flow and glomerular filtration rate as well as renal sodium and lithium excretion were not affected. In conclusion, acute administration of GLP-1 in patients with type 2 diabetes leads to a positive chronotropic effect, but in contrast to healthy individuals, cardiac output does not increase in patients with type 2 diabetes. Renal hemodynamics and sodium excretion are not affected. PMID:26956188

  20. Effects of long-term caffeine consumption on renal function in spontaneously hypertensive heart failure prone rats.

    PubMed

    Tofovic, S P; Jackson, E K

    1999-03-01

    Our previous studies supported the hypothesis that prolonged administration of caffeine to animals with high-renin hypertension causes progressive deterioration of renal function. However, thus far this hypothesis has been tested with only a few animal models of hypertension. The aim of this study was to test this hypothesis further by investigating the effects of long-term caffeine consumption on renal function in adult spontaneously hypertensive heart failure (SHHF/Mcc-fa(cp)) rats, another model of high-renin hypertension. Lean, male, 9-month-old SHHF/Mcc-fa(cp) rats were randomized to receive either normal drinking water (control group) or drinking water containing 0.1% caffeine (caffeine group) for 20 weeks. No changes in body weight, food and fluid intake, urine volume, and sodium and potassium excretion were found in conscious SHHF/Mcc-fa(cp) rats after 10 or 20 weeks of caffeine treatment. However, caffeine treatment accelerated the time-related decline in renal function and augmented urinary protein excretion. Ten weeks into the protocol, creatinine clearance was 3.6+/-0.4 and 5.7+/-0.9 L/kg/day in the caffeine group and control group, respectively (p<0.02), whereas 20 weeks into the study, creatinine clearance was similarly diminished in both groups. Proteinuria was greater in the caffeine group compared with the control group at both 10 (928+/-131 vs. 439+/-21 mg/kg/day, respectively; p<0.02) and 20 weeks (1,202+/-196 vs. 603+/-30 mg/kg/day, respectively; p<0.01) into the protocol. After 20 weeks, all animals were anesthetized and instrumented. Caffeine treatment for 20 weeks had no effects on blood pressure, heart rate, or vascular resistance in four examined vascular beds (abdominal aorta and renal, carotid, and mesenteric arteries). No changes in renal hemodynamics and electrolyte excretion were found, whereas significantly lower glomerular filtration rate (GFR; inulin clearance) and creatinine clearance (p<0.05) were observed in caffeine

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

    PubMed

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

    2016-01-01

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

  2. Hypotensive effect of the nitrosyl ruthenium complex nitric oxide donor in renal hypertensive rats.

    PubMed

    de Gaitani, Cristiane Masetto; de Melo, Miriam C C; Lunardi, Claure N; de S Oliveira, Fabiana; da Silva, Roberto S; Bendhack, Lusiane M

    2009-05-01

    We have described a new compound (trans-[RuCl([15]aneN(4))NO](2+)), which in vitro releases NO by the action of a reducing agent such as catecholamines. We investigated the effect of this NO donor in lowering the mean arterial pressure (MAP) in severe and moderate renal hypertensive 2K-1C rats. MAP was measured before and after intravenous in bolus injection of the compound in conscious 2K-1C and normotensive (2K) rats. In the hypertensive rats (basal 196.70+/-8.70mmHg, n=5), the MAP was reduced in -34.25+/-13.50mmHg (P<0.05) 6h after administration of 10mmol/L/Kg of the compound in bolus. In normotensive rats the compound had no effect. We have also studied the effect of the injection of 0.1mmol/L/Kg in normotensive (basal 118.20+/-11.25mmHg, n=4), moderate (basal 160.90+/-2.30mmHg, n=6), and severe hypertensive rats (basal 202.46+/-16.74 mmHg, n=6). The compound at the dose of 0.1mmol/L/Kg did not have effect (P>0.05) on MAP of normotensive and moderate hypertensive rats. However, in the severe hypertensive rats (basal 202.46+/-16.70mmHg, n=6) there was a significant reduction on the MAP of -28.64+/-12.45mmHg. The NO donor reduced the MAP of all hypertensive rats in the dose of 10mmol/L/Kg and in the severe hypertensive rats at the dose of 0.1mmol/L/Kg. The compound was not cytotoxic to the rat aortic vascular smooth muscle cells in the concentration of 0.1mmol/L/Kg that produced the maximum relaxation. PMID:19114114

  3. Effects of dietary K on cell-surface expression of renal ion channels and transporters.

    PubMed

    Frindt, Gustavo; Palmer, Lawrence G

    2010-10-01

    Changes in apical surface expression of ion channels and transporters in the superficial rat renal cortex were assessed using biotinylation and immunoblotting during alterations in dietary K intake. A high-K diet increased, and a low-K diet decreased, both the overall and surface abundance of the β- and γ-subunits of the epithelial Na channel (ENaC). In the case of γ-ENaC, the effect was specific for the 65-kDa cleaved form of the protein. The overall amount of α-ENAC was also increased with increasing K intake. The total expression of the secretory K(+) channels (ROMK) increased with a high-K diet and decreased with a low-K diet. The surface expression of ROMK increased with high K intake but was not significantly altered by a low-K diet. In contrast, the amounts of total and surface protein representing the thiazide-sensitive NaCl cotransporter (NCC) decreased with increasing K intake. We conclude that modulation of K(+) secretion in response to changes in dietary K intake involves changes in apical K(+) permeability through regulation of K(+) channels and in driving force subsequent to alterations in both Na delivery to the distal nephron and Na(+) uptake across the apical membrane of the K(+) secretory cells. PMID:20702602

  4. Effects of Parvovirus B19 Infection in Renal Transplant Recipients: A Retrospective Review of Three Cases.

    PubMed

    Krishnan, Prathik; Ramadas, Poornima; Rajendran, Prejith P; Madhavan, Parvathy; Alex, Asha; Jayaschandran, Vivek; Humayun, Shaesta G; Ali, Nicole; Sachdeva, Mala; Flecha, Antonette; Basu, Amit; Bhaskaran, Madhu; Molmenti, Ernesto P

    2015-06-01

    Parvovirus B19 (PVB19) is a DNA virus which causes clinically relevant infection in renal transplant recipients (RTR) leading to significant morbidity. Manifestations include erythropoietin resistant anemia, proteinuria, and glomerulosclerosis in the allograft. Severe infection may require administration of intravenous immunoglobulin, reduction in immunosuppression and transfusions. The major challenge in managing and preventing the infection in RTR involves the act of balancing the decreased level of immunosuppression and the risk of rejection. The objective of this article is to understand the importance of PVB19 infection and its outcome in RTR. We reviewed the medical records of three RTR with confirmed PVB19 infection and recorded patient information including demographics, clinical and laboratory data, management, and outcome. The average time of occurrence of PVB19 infection as transplant was 8.6 weeks and they presented with symptomatic anemia. Elevated creatinine values were noted in two of them. Following treatment, anemia improved and creatinine values returned to baseline. One of them developed an early relapse and had to be treated once again similarly. We emphasize the importance of maintaining a high index of suspicion for PVB19 infection in patients with anemia in the posttransplant phase, especially in patients on higher doses of immunosuppressants. Early and proper treatment can prevent worsening clinical condition and possible effects on the allograft. PMID:26060378

  5. Renal effects of BRAF inhibitors: a systematic review by the Cancer and the Kidney International Network

    PubMed Central

    Wanchoo, Rimda; Jhaveri, Kenar D.; Deray, Gilbert; Launay-Vacher, Vincent

    2016-01-01

    Advanced melanoma has been traditionally unresponsive to standard chemotherapy agents and used to have a dismal prognosis. Genetically targeted small-molecule inhibitors of the oncogenic BRAF V600 mutation or a downstream signaling partner (MEK mitogen-activated protein kinase) are effective treatment options for the 40–50% of melanomas that harbor mutations in BRAF. Selective BRAF and MEK inhibitors induce frequent and dramatic objective responses and markedly improve survival compared with cytotoxic chemotherapy. In the past decade after discovery of this mutation, drugs such as vemurafenib and dabrafenib have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency for the treatment of V600-mutated melanomas. While the initial trials did not signal any renal toxicities with the BRAF inhibitors, recent case reports, case series and FDA adverse reporting systems have uncovered significant nephrotoxicities with these agents. In this article, we systematically review the nephrotoxicities of these agents. Based on recently published data, it appears that there are lower rates of kidney disease and cutaneous lesions seen with dabrafenib compared with vemurafenib. The pathology reported in the few kidney biopsies done so far are suggestive of tubulo interstitial damage with an acute and chronic component. Electrolyte disorders such as hypokalemia, hyponatremia and hypophosphatemia have been reported as well. Routine monitoring of serum creatinine and electrolytes and calculation of glomerular filtration rate prior to the first administration when treating with dabrafenib and vemurafenib are essential. PMID:26985376

  6. Nephroprotective Effect of POLYCAN on Acute Renal Failure Induced by Cisplatin in Rats

    PubMed Central

    Ku, Sae-Kwang; Lee, Young-Joon; Lee, Sung-Dong; Cho, Hyung-Rae; Moon, Seung-Bae; Kim, Ki-Young; Kwon, Young-Sam; Kim, Joo Wan

    2012-01-01

    We performed to evaluate the effect of POLYCAN (β-glucan) on cisplatin-(CDDP-)induced acute renal failure (ARF) in rats. POLYCAN was administered orally once a day for 32 days. Each of 8 rats per group was selected based on the body weight (BW) after acclimatization and they were sacrificed at 5 days after CDDP injection. There was significant (P < 0.05) increase of BW after CDDP dosing in all POLYCAN groups than vehicle control and significant (P < 0.01 or P < 0.05) decrease of absolute and relative kidney weight were detected in all POLYCAN groups compared with vehicle control. In addition, serum BUN and creatinine level in all POLYCAN groups were significantly (P < 0.01 or P < 0.05) lower than vehicle control and the percentage of degenerative regions significantly (P < 0.01) decreased in all POLYCAN groups. As the results of CDDP-induced ARF process, dramatic decrease of the BW, increase of the kidney weight, serum BUN, and creatinine level were detected in vehicle control group compared with sham control group. The changes by CDDP-induced ARF process in POLYCAN groups were significantly and dose-dependently improved compared with vehicle control group. Therefore, POLYCAN has enough potential to develop as a new agent of prevention or treatment for ARF. PMID:23738131

  7. The effect of slice thickness on quantitation of in vivo renal volume with cine computed tomography

    SciTech Connect

    Lerman, L.O.; Bentley, M.D.; Bell, M.R.; Rumberger, J.A.; Romero, J.C. )

    1990-02-26

    The development of fast computed tomography (CT) scanners allows the accurate quantitations of the volume (V) of the in-vivo kidney (K) and its component tissues, using 3 mm thick slices. Utilizing thicker slices may potentially enable the use of shorter scan times with less exposure to contrast media. To determine the relative accuracy of such scans, the right Ks of 14 anesthetized dogs were first scanned, using 3mm thick slices, after a venous bolus injection of iohexol (0.5 cc/kg). The images were then averaged to produce 6 and 10 mm thick slices, and the Vs of the Ks, and their cortical and medullary Vs, determined after boundary identification. Following the scans, the Ks were excised and their Vs determined post-mortem by fluid displacement. The whole K Vs obtained with the 6 and 10 mm thick slices correlated well with those obtained with the 3 mm thick slices. The difference between the in vivo and the post-mortem renal and medullary Vs was consistent with the blood, filtrate and urine contents of the in vivo kidney. In conclusion, the use of 6 and 10 mm thick slices resulted in an overestimation of the in vivo cortical V due to a partial volume effect, which was reflected in a consistent overestimation of KV.

  8. Effect of stimulation of afferent renal nerves on plasma levels of vasopressin

    SciTech Connect

    Caverson, M.M.; Ciriello, J.

    1987-04-01

    Experiments were done in ..cap alpha..-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1/sup 0/) component locked in time with the stimulus and a secondary (2/sup 0/) component that had a long onset latency and that outlasted the stimulation period. The 1/sup 0/ and 2/sup 0/ components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockage with hexamethonium bromide and atropine methylbromide abolished the 1/sup 0/ component. Administration of the vasopressin V/sub 1/-vascular receptor antagonist d(CH/sub 2/)/sub 5/ VAVP during autonomic blockade abolished the 2/sup 0/C component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after simulation were not significantly different from control values. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure.

  9. Adverse Renal and Metabolic Effects Associated with Oral Sodium Phosphate Bowel Preparation

    PubMed Central

    Heher, Eliot C.; Thier, Samuel O.; Rennke, Helmut; Humphreys, Benjamin D.

    2008-01-01

    Colorectal cancer can be prevented by the removal of adenomatous polyps during screening colonoscopy, but adequate bowel preparation is required. Oral sodium phosphate (OSP), an effective bowel purgative, is available over the counter and requires a substantially lower volume than polyethylene glycol-based preparative agents. Accumulating reports implicate OSP in electrolyte disturbances as well as acute kidney injury (AKI) in a syndrome termed phosphate nephropathy (a form of nephrocalcinosis). Despite published case reports and case series, the actual incidence, risk factors, and natural history of phosphate nephropathy remain largely undefined. Several recent observational studies have provided new information on these important issues while supporting a link between OSP and acute phosphate nephropathy as well as the development of chronic kidney disease in elderly patients, many of whom had a normal serum creatinine at the time of OSP ingestion. This review summarizes current knowledge about the renal complications of OSP, risk factors for its development, and the pathophysiology of acute and chronic kidney damage in nephrocalcinosis. PMID:18596115

  10. Renoprotective effect of Egyptian cape gooseberry fruit (Physalis peruviana L.) against acute renal injury in rats.

    PubMed

    Ahmed, Lamiaa Ali

    2014-01-01

    This study aimed to evaluate the renoprotective effect of Physalis peruviana L. extract (PPE) on acute renal injury in rats. Adult male rats (n = 36) were divided into six groups that were fed with basal diet throughout the experiment (33 days). The first group was normal group, the second and the third groups were administered orally with 100 and 150 mg PPE/kg body weight (BW) respectively, the fourth group was injected intraperitoneally with 5 mg/kg BW cisplatin once on the 28th day to induced ARI, and the fifth and sixth groups were treated like the second and the third groups and were injected with cisplatin on the 28th day. Many bioactive compounds were found in PPE. PPE did not cause any changes in the second and third groups compared to normal control group. Administration of PPE prior to cisplatin injection caused significant reduction in relative kidney weight, serum creatinine, urea, blood urea nitrogen, and significant increments in body weight, feed intake, total protein, albumin, and total globulin compared to cisplatin group. Pretreatment with PPE improved kidney histology and diminished the level of thiobarbituric acid reactive substances and enhanced other antioxidant enzymes in kidney homogenate compared to cisplatin group. PMID:24757415

  11. Renoprotective Effect of Egyptian Cape Gooseberry Fruit (Physalis peruviana L.) against Acute Renal Injury in Rats

    PubMed Central

    Ahmed, Lamiaa Ali

    2014-01-01

    This study aimed to evaluate the renoprotective effect of Physalis peruviana L. extract (PPE) on acute renal injury in rats. Adult male rats (n = 36) were divided into six groups that were fed with basal diet throughout the experiment (33 days). The first group was normal group, the second and the third groups were administered orally with 100 and 150 mg PPE/kg body weight (BW) respectively, the fourth group was injected intraperitoneally with 5 mg/kg BW cisplatin once on the 28th day to induced ARI, and the fifth and sixth groups were treated like the second and the third groups and were injected with cisplatin on the 28th day. Many bioactive compounds were found in PPE. PPE did not cause any changes in the second and third groups compared to normal control group. Administration of PPE prior to cisplatin injection caused significant reduction in relative kidney weight, serum creatinine, urea, blood urea nitrogen, and significant increments in body weight, feed intake, total protein, albumin, and total globulin compared to cisplatin group. Pretreatment with PPE improved kidney histology and diminished the level of thiobarbituric acid reactive substances and enhanced other antioxidant enzymes in kidney homogenate compared to cisplatin group. PMID:24757415

  12. Nephroprotective Effect of POLYCAN on Acute Renal Failure Induced by Cisplatin in Rats.

    PubMed

    Ku, Sae-Kwang; Lee, Young-Joon; Lee, Sung-Dong; Cho, Hyung-Rae; Moon, Seung-Bae; Kim, Ki-Young; Kwon, Young-Sam; Kim, Joo Wan

    2012-01-01

    We performed to evaluate the effect of POLYCAN (β-glucan) on cisplatin-(CDDP-)induced acute renal failure (ARF) in rats. POLYCAN was administered orally once a day for 32 days. Each of 8 rats per group was selected based on the body weight (BW) after acclimatization and they were sacrificed at 5 days after CDDP injection. There was significant (P < 0.05) increase of BW after CDDP dosing in all POLYCAN groups than vehicle control and significant (P < 0.01 or P < 0.05) decrease of absolute and relative kidney weight were detected in all POLYCAN groups compared with vehicle control. In addition, serum BUN and creatinine level in all POLYCAN groups were significantly (P < 0.01 or P < 0.05) lower than vehicle control and the percentage of degenerative regions significantly (P < 0.01) decreased in all POLYCAN groups. As the results of CDDP-induced ARF process, dramatic decrease of the BW, increase of the kidney weight, serum BUN, and creatinine level were detected in vehicle control group compared with sham control group. The changes by CDDP-induced ARF process in POLYCAN groups were significantly and dose-dependently improved compared with vehicle control group. Therefore, POLYCAN has enough potential to develop as a new agent of prevention or treatment for ARF. PMID:23738131

  13. Renal effects of BRAF inhibitors: a systematic review by the Cancer and the Kidney International Network.

    PubMed

    Wanchoo, Rimda; Jhaveri, Kenar D; Deray, Gilbert; Launay-Vacher, Vincent

    2016-04-01

    Advanced melanoma has been traditionally unresponsive to standard chemotherapy agents and used to have a dismal prognosis. Genetically targeted small-molecule inhibitors of the oncogenic BRAF V600 mutation or a downstream signaling partner (MEK mitogen-activated protein kinase) are effective treatment options for the 40-50% of melanomas that harbor mutations in BRAF. Selective BRAF and MEK inhibitors induce frequent and dramatic objective responses and markedly improve survival compared with cytotoxic chemotherapy. In the past decade after discovery of this mutation, drugs such as vemurafenib and dabrafenib have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency for the treatment of V600-mutated melanomas. While the initial trials did not signal any renal toxicities with the BRAF inhibitors, recent case reports, case series and FDA adverse reporting systems have uncovered significant nephrotoxicities with these agents. In this article, we systematically review the nephrotoxicities of these agents. Based on recently published data, it appears that there are lower rates of kidney disease and cutaneous lesions seen with dabrafenib compared with vemurafenib. The pathology reported in the few kidney biopsies done so far are suggestive of tubulo interstitial damage with an acute and chronic component. Electrolyte disorders such as hypokalemia, hyponatremia and hypophosphatemia have been reported as well. Routine monitoring of serum creatinine and electrolytes and calculation of glomerular filtration rate prior to the first administration when treating with dabrafenib and vemurafenib are essential. PMID:26985376

  14. Prostaglandin-E1 has a protective effect on renal ischemia/reperfusion-induced oxidative stress and inflammation mediated gastric damage in rats.

    PubMed

    Gezginci-Oktayoglu, Selda; Orhan, Nurcan; Bolkent, Sehnaz

    2016-07-01

    Gastrointestinal complications are frequent in renal transplant recipients. In this regard, renal ischemia/reperfusion injury (IRI)-induced gastric damage seems to be important and there is no data available on the mechanism of this pathology. Because of its anti-inflammatory and anti-oxidant properties, it can be suggested that prostaglandin-E1 (PGE1) protects cells from renal IRI-induced gastric damage. The aim of this study was to investigate the molecular mechanisms of gastric damage induced by renal IRI and the effect of PGE1 on these mechanisms. We set an experiment with four different animal groups: physiological saline-injected and sham-operated rats, PGE1 (20μg/kg)-administered and sham operated rats, renal IRI subjected rats, and PGE1-administered and renal IRI subjected rats. The protective effect of PGE1 on renal IRI-induced gastric damage was determined based on reduced histological damage and lactate dehydrogenase activity. Moreover, we demonstrated that PGE1 shows its protective effect through reducing the production of reactive oxygen species and malondialdehyde levels. During histological examination, we observed the presence of common mononuclear cell infiltration. Therefore, pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β levels were measured and it has been shown that PGE1 suppressed both cytokines. Furthermore, it was found that PGE1 reduced the number of NF-κB(+) and caspase-3(+) inflammatory cells, and also NF-κB DNA-binding activity, while increasing proliferating cell nuclear antigen(+) epithelial cells in the stomach tissue of rats subjected to renal IR. Our data showed that PGE1 has a protective effect on renal IRI-induced oxidative stress and inflammation mediated gastric damage in rats. PMID:27135545

  15. An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure

    PubMed Central

    Zhang, Zhi-Hao; Vaziri, Nosratola D.; Wei, Feng; Cheng, Xian-Long; Bai, Xu; Zhao, Ying-Yong

    2016-01-01

    Chronic renal failure (CRF) is a major public health problem worldwide. Earlier studies have revealed salutary effects of rhubarb extracts in CRF. In this study, we employed lipidomic and metabolomic approaches to identify the plasma biomarkers and to determine the effect of treatment with petroleum ether, ethyl acetate and n-butanol extracts of rhubarb in a rat model of CRF with adenine-induced chronic tubulointerstitial nephropathy. In addition, clinical biochemistry, histological evaluation and pro-fibrotic protein expression were analyzed. Significant changes were found between the CRF and control groups representing characteristic phenotypes of rats with CRF. Treatment with the three rhubarb extracts improved renal injury and dysfunction, either fully or partially reversed the plasma metabolites abnormalities and attenuated upregulation of pro-fibrotic proteins including TGF-β1, α-SMA, PAI-1, CTGF, FN and collagen-1. The nephroprotective effect of ethyl acetate extract was better than other extracts. The differential metabolites were closely associated with glycerophospholipid, fatty acid and amino acid metabolisms. The results revealed a strong link between renal tubulointerstitial fibrosis and glycerophospholipid metabolism and L-carnitine metabolism in the development of CRF. Amelioration of CRF with the three rhubarb extracts was associated with the delayed development and/or reversal the disorders in key metabolites associated with adenine-induced CRF. PMID:26903149

  16. Dual-head lithotripsy in synchronous mode: Acute effect on renal function and morphology in the pig

    PubMed Central

    Handa, Rajash K.; McAteer, James A.; Willis, Lynn R.; Pishchalnikov, Yuri A.; Connors, Bret A.; Ying, Jun; Lingeman, James E.; Evan, Andrew P.

    2008-01-01

    Objective Lithotripters with two shock heads are now available for use in treating patients. However, little information is available by which to judge the safety of treatment with dual pulses. A study was conducted to assess the effect of dual-head lithotripsy on renal function and morphology in a pig model of shock wave (SW) injury. Methods A dual-head electrohydraulic lithotripter (Direx Duet) was used to treat the lower renal pole of anesthetized pigs with a clinical dose of SWs (2400 dual SWs; n=10) delivered in synchronous mode (i.e. both heads fired simultaneously). For comparison, pigs were treated with either 2400 SWs (n=12) or 4800 SWs (n=8) with a conventional electrohydraulic lithotripter (Dornier HM3). Results Dual SW treatment with the Duet lithotripter caused a decline in glomerular filtration rate (GFR, 4.1 ± 1.9 ml/min) with a trend for effective renal plasma flow (RPF, 31 ± 19 ml/min) to also fall. These changes in renal hemodynamics were comparable to decreases in GFR and RPF in response to treatment with 2400 SWs (4.8 ± 0.8 ml/min and 32 ± 10 ml/min, respectively) or 4800 SWs (5.4 ± 1.0 ml/min and 68 ± 14 ml/min, respectively) with the HM3 lithotripter. Linear association analysis showed that the functional response to dual-pulse SWs was less predictable than with conventional SWs. Morphological quantitation of kidney damage expressed as percentage of functional renal volume (FRV), showed that tissue injury with 2400 paired SWs with the Duet (0.96± 0.39% FRV, n=8) was comparable to injury produced by either 2400 single SWs (1.08±0.38% FRV, n=6), or 4800 single SWs (2.71±1.02% FRV, n=6) with the HM3. However, morphological damage appeared less consistent with the Duet (measurable in only 5 of 8 kidneys) than that observed with the HM3 (measurable in all 12 kidneys). Acoustic output and the timing of dual SWs in synchronous mode increased in variability as the electrodes aged, affecting the amplitude and targeting of focal pressures

  17. The protective effects of methyl jasmonate against adriamycin--induced hepatic and renal toxicities.

    PubMed

    Kosoko, A M; Molokwu, C J; Farombi, E O; Ademowo, O G

    2012-12-01

    The aim of the study was to investigate the protective effect of methyl jasmonate (MJ) in adriamycin (ADR) induced hepatic and renal toxicities. 36 BALB/c mice were randomly divided into control, ADR (20 mg/kg), MJ (50 mg/kg) only, MJ (100 mg/kg) only, MJ (50 mg/ kg) + ADR, MJ (100 mg/kg) + ADR groups (n = 6). The 2 doses of MJ was administered for 7 days in MJ only groups, ADR was administered intraperitoneally on the 8th day after pretreatment with the 2 different doses of MJ while ADR was administered on the 8th day only for the ADR only group. The malondialdehyde (MDA), glutathione (GSH), H2O2 generation, superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine in the liver, kidneys and serum samples as applicable were estimated. Tissue MDA, H2O2 generation, and GST activity were markedly elevated while GSH content, CAT and SOD activities were significantly reduced in the tissues when compared to the control (p < 0.05). Pretreatment with MJ ameliorated ADR toxicities, with a significant reduction in serum urea concentration, ALT activity, MDA level, H2O2 generation, GST activity and a significant elevation in GSH content, CAT and SOD activities in the organ tissues. MJ induced significant reduction in MDA level and increase of GSH content in liver and kidney tissues. This study suggests that MJ may play an overall protective effect on ADR-induced toxicities in liver and kidneys and the inhibition of tissue peroxidative damage might contribute to this beneficial effect. PMID:23678646

  18. Brazilin exerts protective effects against renal ischemia-reperfusion injury by inhibiting the NF-κB signaling pathway.

    PubMed

    Jia, Yanyan; Zhao, Jinyi; Liu, Meiyou; Li, Bingling; Song, Ying; Li, Yuwen; Wen, Aidong; Shi, Lei

    2016-07-01

    Renal ischemia-reperfusion (I/R) injury is associated with high morbidity and mortality as there is currently no available effective therapeutic strategy with which to treat this injury. Thus, the aim of this study was to investigate the potential protective effects of brazilin, a major active component of the Chinese medicine Caesalpinia sappan L., against renal I/R injury in vitro and in vivo. Rats were subjected to removal of the right kidney and I/R injury to the left kidney (ischemia for 45 min followed by reperfusion for 24 h). Treatment with brazilin (30 mg/kg, administered intravenously at 30 min prior to ischemia) led to the reversal of I/R-induced changes in serum creatinine (Scr) and blood urea nitrogen (BUN) levels, and also attenuated the histopathological damage induced by I/R. Furthermore, TUNEL assay revealed that brazilin reduced cell necrosis, and significantly decreased the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in renal tissue. Moreover, HK-2 cells were used in order to elucidate the mechanisms responsible for the protective effects of brazilin. The levels of phosphorylated IκBα and the nuclear translocation of nuclear factor-κB (NF-κB) were all evidently decreased by brazilin. These findings suggested that pre-treatment with brazilin protects against I/R-induced renal damage and suppresses the inflammatory response by inhibiting the activation of the NF-κB signaling pathway. PMID:27247107

  19. Effect of renal insufficiency on the active transport of calcium by the small intestine

    PubMed Central

    Baerg, Richard D.; Kimberg, Daniel V.; Gershon, Elaine

    1970-01-01

    The intestinal absorption of calcium is often depressed in patients with chronic renal insufficiency. Furthermore, the malabsorption of calcium and the osteodystrophy which occur in association with chronic renal disease are often “resistant” to vitamin D; the basis for this resistance remains uncertain however. Recent studies by others have emphasized the role of an abnormality in the metabolism of vitamin D in accounting for the alterations in the calcium absorption and the apparent vitamin D-resistance which accompany the uremic syndrome. The present studies with an experimentally uremic animal model demonstrate a defect in the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to the semistarvation associated with renal insufficiency and cannot be corrected by the administration of physiologic amounts of vitamin D3: it is reversed by massive doses of the vitamin. Neither the metabolism of vitamin D3 nor the levels of calcium binding protein activity in the duodenal mucosa are affected by renal insufficiency under the conditions employed in the present studies. The results of the present studies strongly suggest that in addition to the recently proposed mechanism involving an interference with the metabolism of vitamin D renal insufficiency also affects the cellular mechanisms for calcium transport in a manner which, while opposite in direction to that of vitamin D, is independent of a direct interaction with the vitamin or its metabolites. PMID:5422027

  20. Effects of fasting during Ramadan on renal function of patients with chronic kidney disease.

    PubMed

    Mbarki, Houda; Tazi, Nada; Najdi, Adil; Tachfouti, Nabil; Arrayhani, Mohamed; Sqalli, Tarik

    2015-03-01

    Fasting during Ramadan is prohibited when an individual's health is endangered. Little work has been published in this direction in patients with chronic kidney disease (CKD). We aimed to evaluate the impact of fasting during Ramadan on the renal function of patients with CKD, adjusting for the initial degree of renal impairment. We prospectively studied 60 patients with CKD (35 females; mean age 45.6 ± 15.8 years). All study patients were older than 15 years, being followed-up at the nephrology clinic for more than six months, having a stable CKD during the preceding six months and who had fasted during Ramadan the previous year. Patients who had a medical contra-indication for fasting were excluded from the study [severe or resistant arterial hypertension, insulin-requiring diabetes, acute renal failure (ARF), active renal disease, repetitive urolithiasis or terminal chronic renal failure]. Statistical analysis was performed in collaboration with the epidemiology lab at the Fez Medical School using the SPSS software version 17. Three of the study patients developed ARF in the first week and four of them at the end of the month of the study period. The risk of developing ARF was significantly higher for patients with baseline creatinine clearance of <60 mL/min/1.73 m 2 . However, the small sample size does not allow us to draw any firm conclusions on fasting during Ramadan in stable CKD patients. Studies on larger numbers of patients are recommended. PMID:25758882

  1. Protective Effect of Cleistocalyx nervosum var. paniala Fruit Extract against Oxidative Renal Damage Caused by Cadmium.

    PubMed

    Poontawee, Warut; Natakankitkul, Surapol; Wongmekiat, Orawan

    2016-01-01

    Cadmium nephrotoxicity is a serious environmental health problem as it will eventually end up with end stage renal disease. The pathobiochemical mechanism of this toxic heavy metal is related to oxidative stress. This study investigated whether Cleistocalyx nervosum var. paniala fruit extract (CNFE) could protect the kidney against oxidative injury caused by cadmium. Initial analysis of the extract revealed antioxidant abilities and high levels of polyphenols, particularly catechin. Its potential renal benefits was further explored in rats treated with vehicle, CNFE, cadmium (2 mg/kg), and cadmium plus CNFE (0.5, 1, 2 g/kg) for four weeks. Oxidative renal injury was developed after cadmium exposure as evidenced by blood urea nitrogen and creatinine retention, glomerular filtration reduction, renal structural damage, together with increased nitric oxide and malondialdehyde, but decreased antioxidant thiols, superoxide dismutase, and catalase in renal tissues. Cadmium-induced nephrotoxicity was diminished in rats supplemented with CNFE, particularly at the doses of 1 and 2 g/kg. It is concluded that CNFE is able to protect against the progression of cadmium nephrotoxicity, mostly via its antioxidant power. The results also point towards a promising role for this naturally-occurring antioxidant to combat other human disorders elicited by disruption of redox homeostasis. PMID:26805807

  2. Evolution

    NASA Astrophysics Data System (ADS)

    Peter, Ulmschneider

    When we are looking for intelligent life outside the Earth, there is a fundamental question: Assuming that life has formed on an extraterrestrial planet, will it also develop toward intelligence? As this is hotly debated, we will now describe the development of life on Earth in more detail in order to show that there are good reasons why evolution should culminate in intelligent beings.

  3. Systematic study of tensor effects in shell evolution

    SciTech Connect

    Wang, Y. Z.; Zhang, X. Z.; Gu, J. Z.; Dong, J. M.

    2011-05-15

    In the framework of the Hartree-Fock-Bogoliubov approach with the Skyrme interactions SLy5, SLy5+T, SLy5+T{sub w}, and several sets of the TIJ parametrizations (Skyrme effective interaction parametrizations including the tensor terms), the effect of the tensor force on the shell evolution at Z,N=8, 20, and 28 is investigated. It is shown that the evolution of the gap (defined as the energy difference between the last occupied and first unoccupied single-particle orbits) with SLy5+T is similar to that with SLy5+T{sub w}, and the gap values with SLy5+T are smaller than those with SLy5+T{sub w} in the cases of Z,N=8, 20. At Z, N = 28, the gap values with SLy5 are smaller than those with SLy5+T and larger than those with SLy5+T{sub w}. To understand these features, we analyze the spin-orbit potentials with and without the tensor contributions and the radial wave functions of relevant orbits. Meanwhile, we find that the deviation of the calculated gaps with SLy5+T{sub w} from the experimental ones is larger than that with SLy5+T. This indicates that SLy5+T{sub w} is not suitable for investigating the properties of the ground-state gap evolution. Finally, it is seen that the gap evolutions with different sets of the TIJ parametrizations are similar to each other except for the ones with T22, and there is almost no difference between the tensor effect in gap evolution with the perturbative method and the one with the complete fitting method.

  4. Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures.

    PubMed

    Kassemi, Mohammad; Thompson, David

    2016-09-01

    An analytic Population Balance Equation model is used to assess the efficacy of citrate, pyrophosphate, and augmented fluid intake as dietary countermeasures aimed at reducing the risk of renal stone formation for astronauts. The model uses the measured biochemical profile of the astronauts as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating renal calculi subject to biochemical changes brought about by administration of these dietary countermeasures. Numerical predictions indicate that an increase in citrate levels beyond its average normal ground-based urinary values is beneficial but only to a limited extent. Unfortunately, results also indicate that any decline in the citrate levels during space travel below its normal urinary values on Earth can easily move the astronaut into the stone-forming risk category. Pyrophosphate is found to be an effective inhibitor since numerical predictions indicate that even at quite small urinary concentrations, it has the potential of shifting the maximum crystal aggregate size to a much smaller and plausibly safer range. Finally, our numerical results predict a decline in urinary volume below 1.5 liters/day can act as a dangerous promoter of renal stone development in microgravity while urinary volume levels of 2.5-3 liters/day can serve as effective space countermeasures. PMID:27279491

  5. Intra-Renal Oxygenation in Rat Kidneys During Water-loading: Effects of COX Inhibition & NO Donation

    PubMed Central

    Ji, Lin; Li, Lu-Ping; Schnitzer, Thomas; Du, Hongyan; Prasad, Pottumarthi V.

    2010-01-01

    Purpose To evaluate intra-renal oxygenation by blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) in rat kidneys during water-loading and to investigate if the nitric oxide donating moiety in naproxcinod could compensate the effect of cyclooxygenase inhibition of naproxen. Materials and Methods Nineteen male Sprague Dawley rats were divided into three groups and dosed with vehicle, naproxen or naproxcinod by gavage for two weeks. On the day of the experiment, hypotonic saline with glucose was infused intravenously to induce water diuresis. BOLD MRI data to monitor renal oxygenation and timed urine samples for estimation of prostaglandins and urine flow were obtained. Results The data in this study is consistent with previous experience in humans in that pre-treatment with naproxen abolished the improvement in medullary oxygenation during water-loading. In addition, the inhibition of prostaglandins by naproxcinod reached similar levels as naproxen but maintained the improvement in oxygenation in renal medulla during water-loading. Conclusion This suggests that naproxcinod may have less nephrotoxicity and that the nitric oxide donating moiety partially compensates for the hemodynamic effects of prostaglandin inhibition by naproxen. PMID:20677266

  6. Effect of breed, age, weight and gender on radiographic renal size in the dog.

    PubMed

    Lobacz, Monika Anna; Sullivan, Martin; Mellor, Dominic; Hammond, Gawain; Labruyère, Julien; Dennis, Ruth

    2012-01-01

    In the adult dog, kidney length has been reported as 2.98 ± 0.44 times the length of L2 on ventrodorsal views and 2.79 ± 0.46 times the length of L2 on lateral radiographs. Our aim was to test the hypothesis that the suggested maximum normal left kidney size is too high, and to evaluate the effect of breed type, gender, weight and age of the dog on kidney size. Abdominal radiographs of 200 dogs with no evidence of concurrent disease that might have an effect on renal size were included in the study. The mean ratio of kidney length to the second lumbar vertebra length was similar to previous reports. For the right lateral view it measured 2.98 ± 0.60 and for the ventrodorsal view 3.02 ± 0.66. Significant differences of this ratio between skull type were present, especially between brachycephalic and dolichocephalic dogs. On the right lateral view brachycephalic dogs had the highest median LK/L2 ratio of 3.1 (3.20 ± 0.40), whereas for dolichocephalic dogs it was 2.8 (2.82 ± 0.50), and for mesaticephalic dogs it was 2.97 (3.01 ± 0.6). A ratio >3.5 was found only in mesaticephalic dogs on the ventrodorsal view. There was a significant difference in the LK/L2 ratio between small (≤10kg) and large breed dogs (>30kg) where small dogs had a significantly higher LK/L2 ratio. There was no statistically significant relation between this ratio and age or gender. The previously reported ratios for kidney size seem valid, but because skull type has an impact on the LK/L2 ratio, a single normal ratio should not be used for all dogs. PMID:22537277

  7. Xanthine effects on renal proximal tubular function and cyclic AMP metabolism.

    PubMed

    Coulson, R; Scheinman, S J

    1989-02-01

    We evaluated the renal effects of xanthines using two in vitro models: the isolated perfused rat kidney (IPRK) and cultured opossum kidney (OK) cells, a continuous cell line that resembles proximal tubule and responds to parathyroid hormone (PTH). 1,3-Diethyl-8-phenylxanthine (DPX) a potent adenosine receptor antagonist, increased urine volume, glomerular filtration rate, vascular resistance and the fractional excretions of Na, K, Ca and Pi in the IPRK. DPX lowered the Na-dependent uptake of Pi by OK cells. By comparison enprofylline, 3-propylxanthine (ENP), a weak adenosine receptor antagonist, produced a slight elevation in glomerular filtration rate but no changes in electrolyte excretion by IPRK or Pi uptake by OK cells. Both DPX and ENP produced negligible elevations in basal IPRK cAMP. A 1-nM bolus of PTH elevated urinary and perfusate cAMP 50- and 10-fold, respectively. PTH-elevated urinary and perfusate cAMP were augmented further 4- to 7-fold with DPX and 3- to 4-fold with ENP (All IPRK experiments used 50 microM xanthine). OK cells produced a 2-fold cAMP response to 10 nM PTH alone. OK cells treated with 50 microM DPX exhibited no increase in basal but a 13-fold increase in PTH-stimulated cell cAMP. The rank order of potency at 50 microM to augment OK cell cAMP with 10 nM PTH was DPX greater than 1,3-dipropyl-8-cyclopentylxanthine (DPC) greater than 1-methyl-3-isobutylxanthine greater than theobromine greater than theophylline greater than caffeine greater than ENP = no effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2537403

  8. Pulmonary Function in Patients with End-Stage Renal Disease: Effects of Hemodialysis and Fluid Overload.

    PubMed

    Yılmaz, Süreyya; Yildirim, Yasar; Yilmaz, Zülfükar; Kara, Ali Veysel; Taylan, Mahsuk; Demir, Melike; Coskunsel, Mehmet; Kadiroglu, Ali Kemal; Yilmaz, Mehmet Emin

    2016-01-01

    BACKGROUND Respiratory system disorders are one of the most prevalent complications in end-stage renal disease patients on hemodialysis. However, the pathogenesis of impaired pulmonary functions has not been completely elucidated in these patients. We designed a study to investigate acute effects of hemodialysis treatment on spirometry parameters, focusing on the relationship between pulmonary function and fluid status in hemodialysis patients. MATERIAL AND METHODS We enrolled 54 hemodialysis patients in this study. Multifrequency bioimpedance analysis (BIA) was used to assess fluid status before and 30 min after the midweek of hemodialysis (HD). Overhydration (OH)/extracellular water (ECW)% ratio was used as an indicator of fluid status. Fluid overload was defined as OH/ECW ≥7%. Spirometry was performed before and after hemodialysis. RESULTS Forced vital capacity (FVC), FVC%, and forced expiratory volume in the first second (FEV1) levels were significantly increased after hemodialysis. FVC, FVC%, FEV1, FEV1%, mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75), FEF25-75%, peak expiratory flow rate (PEFR), and PEFR% were significantly lower in patients with fluid overload than in those without. OH/ECW ratio was negatively correlated with FVC, FVC%, FEV1, FEV1%, FEF25-75, FEF25-75%, PEFR, and PEFR%. Stepwise multiple regression analysis revealed that male sex and increased ultrafiltration volume were independently associated with higher FVC, whereas increased age and OH/ECW ratio were independently associated with lower FVC. CONCLUSIONS Fluid overload is closely associated with restrictive and obstructive respiratory abnormalities in HD patients. In addition, hemodialysis has a beneficial effect on pulmonary function tests, which may be due to reduction of volume overload. PMID:27497672

  9. Cardiovascular and Renal Effects of Bromocriptine in Diabetic Patients with Stage 4 Chronic Kidney Disease

    PubMed Central

    Mejía-Rodríguez, Oliva; Herrera-Abarca, Jorge E.; Ceballos-Reyes, Guillermo; Avila-Diaz, Marcela; Prado-Uribe, Carmen; Belio-Caro, Francisco; Salinas-González, Antonio; Vega-Gomez, Helios; Alvarez-Aguilar, Cleto; Lindholm, Bengt; García-López, Elvia; Paniagua, Ramón

    2013-01-01

    Objective. The objective of this study was to investigate the effect of bromocriptine (BEC) on left ventricular mass index (LVMI) and residual renal function (RRF) in chronic kidney disease (CKD) patients with type 2 diabetes (T2D). Research Design and Methods. A 6-month double-blind randomized controlled trial was conducted in 28 patients with T2D and stage 4 CKD with increased LVMI. Fourteen patients received BEC (2.5 mg, initially 1 tablet with subsequent increase to three times a day) and 14 received a placebo (PBO; initially 1 tablet with subsequent increase to three times a day). Cardiovascular changes were assessed by monitoring 24 h ambulatory blood pressure, two-dimensional-guided M-mode echocardiography, and N-terminal brain natriuretic peptide (NT-proBNP) plasma levels. RRF was evaluated by creatinine clearance and cystatin-C plasma levels. Results. Both BEC and PBO groups decreased blood pressure—but the effect was more pronounced in the BEC group. Average 24 h, diurnal and nocturnal blood pressures, and circadian profile showed improved values compared to the PBO group; LVMI decreased by 14% in BEC and increased by 8% in PBO group. NT-proBNP decreased in BEC (0.54 ± 0.15 to 0.32 ± 0.17 pg/mL) and increased in PBO (0.37 ± 0.15 to 0.64 ± 0.17 pg/mL). Creatinine clearance did not change in the BEC group and decreased in the PBO group. Conclusions. BEC resulted in a decrease on blood pressure and LVMI. BEC also prevented the progression of CKD while maintaining the creatinine clearance unchanged. PMID:23984312

  10. Pulmonary Function in Patients with End-Stage Renal Disease: Effects of Hemodialysis and Fluid Overload

    PubMed Central

    Yilmaz, Süreyya; Yildirim, Yasar; Yilmaz, Zülfükar; Kara, Ali Veysel; Taylan, Mahsuk; Demir, Melike; Coskunsel, Mehmet; Kadiroglu, Ali Kemal; Yilmaz, Mehmet Emin

    2016-01-01

    Background Respiratory system disorders are one of the most prevalent complications in end-stage renal disease patients on hemodialysis. However, the pathogenesis of impaired pulmonary functions has not been completely elucidated in these patients. We designed a study to investigate acute effects of hemodialysis treatment on spirometry parameters, focusing on the relationship between pulmonary function and fluid status in hemodialysis patients. Material/Methods We enrolled 54 hemodialysis patients in this study. Multifrequency bioimpedance analysis (BIA) was used to assess fluid status before and 30 min after the midweek of hemodialysis (HD). Overhydration (OH)/extracellular water (ECW)% ratio was used as an indicator of fluid status. Fluid overload was defined as OH/ECW ≥7%. Spirometry was performed before and after hemodialysis. Results Forced vital capacity (FVC), FVC%, and forced expiratory volume in the first second (FEV1) levels were significantly increased after hemodialysis. FVC, FVC%, FEV1, FEV1%, mean forced expiratory flow between 25% and 75% of the FVC (FEF25–75), FEF25–75%, peak expiratory flow rate (PEFR), and PEFR% were significantly lower in patients with fluid overload than in those without. OH/ECW ratio was negatively correlated with FVC, FVC%, FEV1, FEV1%, FEF25–75, FEF25–75%, PEFR, and PEFR%. Stepwise multiple regression analysis revealed that male sex and increased ultrafiltration volume were independently associated with higher FVC, whereas increased age and OH/ECW ratio were independently associated with lower FVC. Conclusions Fluid overload is closely associated with restrictive and obstructive respiratory abnormalities in HD patients. In addition, hemodialysis has a beneficial effect on pulmonary function tests, which may be due to reduction of volume overload. PMID:27497672

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

    SciTech Connect

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

    1988-05-01

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

  12. Effect of Hemodialysis on Plasma Myeloperoxidase Activity in End Stage Renal Disease Patients.

    PubMed

    Rao, A Madhusudhana; Apoorva, R; Anand, Usha; Anand, C V; Venu, G

    2012-07-01

    End stage renal disease (ESRD) patients on hemodialysis (HD) have an increased oxidative stress, with a high risk of atherosclerosis and other co-morbid conditions. Recent studies have suggested that myeloperoxidase (MPO)-mediated oxidative stress may play a role in the pathogenesis of cardiovascular complications in dialysis patients. Furthermore, dialysis treatment 'per se' can aggravate oxidative stress. Hence this study was designed to determine whether HD leads to an alteration in the plasma levels of MPO and malondialdehyde (MDA), a marker of oxidative stress in ESRD patients on maintenance HD. To study the effect of HD, plasma MPO and MDA were determined before and after HD in forty ESRD patients (24 men and 16 women, age between 8 and 71 years, median being 40.5 years) on maintenance HD. Plasma MPO and MDA were assayed by spectrophotometric methods. Haematological and other biochemical parameters were obtained from patients' case records. Plasma MPO and MDA levels were significantly higher after HD when compared with pre-dialysis levels (p < 0.05). There was no correlation between MPO and MDA (r = 0.184, p = 0.10) and other biochemical parameters (p > 0.05). However, there was a significant correlation between MPO and MDA with haemodialysis vintage (p < 0.05). In univariate regression analysis duration of HD (β = 1.470, p = 0.045, β = 0.388, p = 0.013), was independently associated with MPO and MDA. Although HD is indispensable for survival of patients with ESRD, it is fraught with undesirable side-effects, such as an increase in the plasma MPO and MDA levels. The elevated levels of MPO contribute to the increased oxidative stress as free radicals are produced by the reaction catalyzed by it. PMID:26405383

  13. Blood pressure responses to renal denervation precede and are independent of the sympathetic and baroreflex effects.

    PubMed

    Grassi, Guido; Seravalle, Gino; Brambilla, Gianmaria; Trabattoni, Daniela; Cuspidi, Cesare; Corso, Rocco; Pieruzzi, Federico; Genovesi, Simonetta; Stella, Andrea; Facchetti, Rita; Spaziani, Domenico; Bartorelli, Antonio; Mancia, Giuseppe

    2015-06-01

    It is still largely unknown whether the neuroadrenergic responses to renal denervation (RD) are involved in its blood pressure (BP)-lowering effects and represent predictors of the BP responses to RD. In 15 treated true resistant hypertensives, we measured before and 15 days, 1, 3, and 6 months after RD clinic, ambulatory and beat-to-beat BP. Measurements included muscle sympathetic nerve traffic (MSNA), spontaneous baroreflex-MSNA sensitivity, and various humoral and metabolic variables. Twelve treated hypertensives served as controls. BP, which was unaffected 15 days after RD, showed a significant decrease during the remaining follow-up period. MSNA and baroreflex did not change at 15-day and 1-month follow-up and showed, respectively, a decrease and a specular increase at 3 and 6 months after RD. No relationship, however, was detected between baseline MSNA and baroreflex, MSNA changes and BP changes. At the 6-month follow-up, the MSNA reduction was similar for magnitude in patients displaying a BP reduction greater or lower the median value. Similarly, the BP reduction detected 6 months after RD was similar in patients displaying a MSNA reduction greater or lower median value. No significant BP and MSNA changes were detected in the control group. Thus, the BP reduction associated with RD seems to precede the MSNA changes and not to display a temporal, qualitative, and quantitative relationship with the MSNA and baroreflex effects. Given the small sample size of the present study further investigations are warranted to confirm the present findings. PMID:25824245

  14. Effect of dexmedetomidine on rats with renal ischemia-reperfusion injury and the expression of tight junction protein in kidney.

    PubMed

    Liu, Yun-En; Tong, Chang-Ci; Zhang, Yu-Biao; Jin, Hong-Xu; Gao, Yan; Hou, Ming-Xiao

    2015-01-01

    To explore the protective effect of dexmedetomidine (Dex) on rats with renal ischemia-reperfusion injury and the influence of Dex on the expression of tight junction protein in kidney. Grouped 40 SPF male rats into 4 groups, sham operation group (group S), ischemia-reperfusion group (group I/R), pretreatment with Dex group (group Pre/Dex), post-treatment with Dex group (group Post/Dex), randomly, 10 rats each group. Rats in group S were anaesthetized and set up with removal of right kidney; rats in group I/R were set up with removal of right kidney and left renal artery clamping for 45 min followed by 60 min reperfusion; rats in group Pre/Dex were intravenous injected with Dex (1 μg/kg) for 30 min after indwelling catheter via femoral vein puncture; rats in group Post/Dex were intravenous injected with Dex (1 μg/kg) for 30 min after left renal reperfusion. The kidneys in each group were made out pathologic slices after 6 h I/R, stained with HE; blood samples were taken with separation plasma, creatinine (Scr) and urea nitrogen (BUN) were detected by automatic biochemical analyzer; IL-1β and TNF-α were detected by Enzyme-linked Immunosorbent Assay (ELISA); the expression level of tight junction protein ZO-1 and protein occludin in kidney were detected by Western-blot. The results of HE staining showed that, comparing to group S, the tissue of kidney in group I/R were damaged heavily with tubules dilatation and inflammation obviously, while lightened in group Pre/Dex and group Post/Dex. The results of detection of renal function and inflammatory factors showed that, comparing to group S, Scr, BUN, IL-1β and TNF-α were all enhanced in group I/R, group Pre/Dex and group Post/Dex, significantly (P < 0.05), while the inflammatory factors in group Pre/Dex and group Post/Dex were lower than in group I/R, significantly (P < 0.05). The results of Western-blot showed that the expression of protein ZO-1 and occludin in group Pre/Dex and group Post/Dex were higher than in

  15. [Effect of Astragali Radix in improving early renal damage in metabolic syndrome rats through ACE2/Mas pathway].

    PubMed

    Wang, Qiong-ying; Liang, Wei; Jiang, Cheng; Li, Ning-yin; Xu, Han; Yang, Mi-na; Lin, Xin; Yu, Heng; Chang, Peng; Yu, Jing

    2015-11-01

    To study the expression of angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang) 1-7 specific receptor Mas protain in renal blood vessels of metabolic syndrome ( MS) rats and its anti-oxidative effect. A total of 80 male SD rats were divided into four groups: the normal control group (NC, the same volume of normal saline), the MS group (high fat diet), the MS + Astragali Radix group (MS + HQ, 6 g x kg(-1) x d(-1) in gavage) and the MS + Valsartan group (MS + XST, 30 mg x kg(-1) x d(-1) in gavage). After four weeks of intervention, their general indexes, biochemical indexes and blood pressure were measured; plasma and renal tissue Ang II, malondialdehyde (MDA) and superoxide demutase (SOD) levels were measured with radioimmunoassay. The protein expressions of Mas receptor, AT1R, ACE and ACE2 were detected by western blot analysis. According to the result, compared with the NC group, the MS group and the MS + HQ group showed significant increases in systolic and diastolic pressures, body weight, fasting glucose, fasting insulin, triglycerides, free fatty acid and Ang II level of MS rats (P < 0.05). The MS + XST group showed notable decreases in systolic and diastolic pressures than that of the MS group. The MS group showed significant increases in the SOD activity and NO level and decrease in the MDA level after being intervened with Astragali Radix. ACE and AT1R protein expressions in renal tissues of the MS group were higher than that in the NC group, but with lower ACE2 and -Mas receptor expressions (all P < 0.05). Compared with the MS group, the MS + HQ group showed significant increase in Mas receptor expression in renal tissues, whereas the MS + XST group showed notable decrease in AT1R (all P < 0.05). In conclusion, Astragali Radix can increase the Mas receptor expressions in renal tissues, decrease ACE expression and change local Ang II, MDA, NO and SOD in kidneys, so as to protect early damages in renal tissues. PMID:27071265

  16. Effects of exercise and excitement on mesenteric and renal dynamics in conscious, unrestrained baboons

    NASA Technical Reports Server (NTRS)

    Vatner, S. F.

    1978-01-01

    Radiotelemetry was used to measure arterial pressure and mesenteric and renal blood flows from nine unrestrained, conscious baboons during periods of rest, moderate exercise, and extreme excitement. A description of the experiments hardware is presented, including artificial depressants phenylcyclidine hydrochloride, 0.5-1.0 mg/kg, and pentobarbital sodium, 15 mg/kg, and an ultrasonic telemetry flow meter. Results showed rising heart rate and arterial pressure coupled with a reduction of mesenteric and renal flows as the level of exercise was increased. These findings are compared with mesenteric and renal flows somewhat above control level, but relatively stable heart rate and arterial pressure, postprandially. Attention is given to a quantitative analysis of the experimental results.

  17. Therapeutic effects of curcumin on the functional disturbances and oxidative stress induced by renal ischemia/reperfusion in rats

    PubMed Central

    Najafi, Houshang; Changizi Ashtiyani, Saeed; Sayedzadeh, Sayed Abolhasan; Mohamadi yarijani, Zeynab; Fakhri, Sajad

    2015-01-01

    Objective: Curcumin has anti-inflammatory and antioxidative properties. The objective of this study was to investigate the therapeutic effects of curcumin on functional disturbances, oxidative stress, and leukocyte infiltration induced by renal ischemia/reperfusion (I/R). Materials and Methods: Animals were randomly divided into 9 groups. The groups with 24-h reperfusion consisted of sham-24h, I/R-24h, and three I/R groups treated with curcumin at 10, 20, or 30 mg kg-1, i.p. after the ischemic period. The 72-h reperfusion groups also included Sham-72h, I/R-72h, I/R treated with curcumin at single dose of 20 mg kg-1, i.p., and I/R group which received three doses of curcumin at 20 mg kg-1, i.p., consecutively. Renal functional injury was assessed by measuring serum creatinine and urea-nitrogen concentrations. Oxidative stress was evaluated by assessment tissue malondialdehyde (MDA) and the ferric reducing/antioxidant power (FRAP) levels. Moreover, renal tissue leukocyte infiltration was measured by histopathology examination. Results: Ischemia/reperfusion resulted in a significant increase in serum concentration of creatinine, urea-nitrogen, tissue MDA level, and leukocytes infiltration as well as reduced FRAP level. Treatment with curcumin in 24-h reperfusion groups could only lead to a significant change in the levels of MDA and FRAP. However, in 72-h reperfusion groups, curcumin was able to correct all functional disturbances, oxidative stress, and leukocytes infiltration with more effectiveness in groups that received three doses of curcumin. Conclusion: The administration of curcumin during 72-h reperfusion following 30 minutes of ischemia can decrease renal oxidative stress and leukocytes infiltration as well as improve kidney function. However, during first 24-h reperfusion, curcumin only decreased oxidative stress. PMID:26693415

  18. Drug utilization evaluation of meropenem and correlation of side effects with renal status of patients in a teaching based hospital.

    PubMed

    Khan, Muhammad Umair; Yousuf, Rabia Ismail; Shoaib, Muhammad Harris

    2014-09-01

    Meropenem is a restricted, broad spectrum and expensive antibiotic. The major consequences of irrational use of restricted antibiotics are increase drug resistance and drug expenditure. The use of antibiotics, specifically restricted antibiotics, must be monitored continuously to increase its adherence to the standard guidelines to avoid such problems. The objective of this study was to evaluate the appropriateness of meropenem use with respect to renal status of patients in a teaching based hospital. A retrospective study was carried out from 1st January 2013 to 30th June 2013 to determine the evaluation of meropenem use in accordance to the criteria developed through national (Infectious disease society of Pakistan) and international guidelines (Health care infection control practices advisory committee). The data was recorded on data collection form by thorough reviewing of patients' medical records. Main outcomes measured were indication, dose, interval, duration, creatinine clearance, complete blood count and culture sensitivity test. Correlation of different variable (side effects and generalized health) was also observed with reference to renal status of patients. Statistical analyses were performed using descriptive statistics. A total of 201 cases of meropenem prescription were identified during the study period. The variable, which was most consistent with the criteria was 'indication', in which 97.52% of meropenem prescription was indicated in diseases encouraged by guidelines. However, the use of meropenem as an empirical therapy was the major problem reported in this study as it adhered to in only 43% of the cases. It was also noted that prevalence of side effects increased when meropenem was prescribed in renal compromised patients, and also observed that generalized health of patients decreased with meronem use in renal unstable patients. Thrombocytopenia was the major problem associated with the meropenem use (37.81%). The study detected various

  19. Protective effects of AT1-receptor blocker and CA antagonist combination on renal function in salt loaded spontaneously hypertensive rats.

    PubMed

    Gjorgjievska, K; Zafirov, D; Jurhar-Pavlova, M; Cekovska, S; Atanasovska, E; Pavlovska, K; Zendelovska, D

    2015-01-01

    Salt sensitive hypertension is known to be a contributing factor for the progression of kidney disease. This study was undertaken to investigate the role of excessive dietary salt on renal function and to evaluate the effect of valsartan and amlodipin given as a combination therapy on blood pressure and parameters specific to the renal function in salt loaded SHR rats. 48 male SHR rats at age of 20 weeks and body weight ranging between 270-350 g were used. SHR rats were divided into 3 groups: control group of rats -SHRC (n = 16) given tab water ad libitum and two salt treated groups in which tab water was replaced with a solution of NaCl (1%) from age of 8 weeks given ad libitum: SHRVAL+AMLO group (n = 16) where investigated drugs were administered at a dose of 10 mg/kg/ b.w. (valsartan) and 5 mg/kg/ b.w. (amlodipin) by gavage and SHR NaCl group (n = 16) that received saline in the same volume and the same time intervals as the SHRVAL+AMLO group. For a period of 12 weeks we have investigated the effect of the VAL+AMLO drug combination on systolic blood pressure (SBP), body weight and renal function tests. Salt loading with 1% solution in the SHR NaCl group has lead to significant increase of blood pressure, proteinuria and decrease in creatinine clearance. Combined treatment with AT1 receptor blocker and calcium antagonist has managed to control blood pressure and ameliorated renal damage. PMID:26076778

  20. Effect of renal function on the pharmacokinetics of fimasartan: a single-dose, open-label, Phase I study

    PubMed Central

    Kim, Seokuee; Lee, Jongtae; Shin, Donghoon; Lim, Kyoung Soo; Kim, Yon Su; Jang, In-Jin; Yu, Kyung-Sang

    2014-01-01

    Background Fimasartan is a novel angiotensin II receptor blocker. Fimasartan is mainly eliminated via biliary excretion, and its urinary elimination is less than 3%. Objective Based on guidance from the United States Food and Drug Administration, a reduced pharmacokinetic (PK) study was conducted to evaluate the effect of renal function on the PK of fimasartan in patients with renal impairment and healthy volunteers. Methods A single centre, single-dose, open-label, healthy volunteer controlled trial was conducted in patients with renal impairment (RI) (estimated glomerular filtration rate lower than 30 mL/min/1.73 m2) and age-, weight- and sex-matched healthy volunteers (estimated glomerular filtration rate higher than 90 mL/min/1.73 m2). All participants received a single oral dose of fimasartan 120 mg, after which serial blood sampling for PK evaluation was conducted. Noncompartmental PK analysis of fimasartan was performed. A mixed-effects model approach was used to identify significant covariates and PK parameters. Results Sixteen subjects were enrolled (8 healthy volunteers and 8 RI patients). The maximum plasma concentrations and areas under the plasma concentration curves of the RI patients were higher than those of the healthy volunteers, with geometric mean ratios of 1.87 and 1.73, respectively. The relative bioavailability of fimasartan from the population PK analysis was 77% higher in the RI patients than in the healthy volunteers. Conclusion The increased drug exposure of fimasartan in RI patients was explained by the increased relative bioavailability. This result can be explained from our knowledge concerning alterations in PK related to renal function. PMID:25336916

  1. Correcting the Shrinkage Effects of Formalin Fixation and Tissue Processing for Renal Tumors: toward Standardization of Pathological Reporting of Tumor Size

    PubMed Central

    Tran, Thu; Sundaram, Chandru P.; Bahler, Clinton D.; Eble, John N.; Grignon, David J.; Monn, M. Francesca; Simper, Novae B.; Cheng, Liang

    2015-01-01

    Given the importance of correctly staging renal cell carcinomas, specific guidelines should be in place for tumor size measurement. While a standard means of renal tumor measurement has not been established, intuitively, tumor size should be based on fresh measurements. We sought to assess the accuracy of postfixation and microscopic measurements of renal tumor size, as compared to fresh measurements and radiographic size. Thirty-four nephrectomy cases performed by a single surgeon were prospectively measured at different time points. The study cases included 23 clear cell renal cell carcinomas, 6 papillary renal cell carcinomas, and 5 other renal tumors. Radiologic tumors were 12.1% larger in diameter than fresh tumors (P<0.01). Furthermore, fresh specimens were 4.6% larger than formalin-fixed specimens (P<0.01), and postfixation measurements were 7.1% greater than microscopic measurements (P<0.01). The overall mean percentage of shrinkage between fresh and histological specimens was 11.4% (P<0.01). Histological processing would cause a tumor stage shift from pT1b to pT1a for two tumors in this study. The shrinkage effects of formalin fixation and histological processing may result in understaging of renal cell carcinomas. The shrinkage factor should be considered when reporting tumor size. PMID:26185538

  2. Effects of size and location of regions of interest examined by use of contrast-enhanced ultrasonography on renal perfusion variables of dogs.

    PubMed

    Macrì, Francesco; Di Pietro, Simona; Liotta, Luigi; Piccionello, Angela Palumbo; Pugliese, Michela; De Majo, Massimo

    2016-08-01

    OBJECTIVE To determine effects of the size and location of regions of interest (ROIs) in the renal cortex of unsedated dogs on renal perfusion variables determined by use of contrast-enhanced ultrasonography (CEUS). ANIMALS 12 client-owned adult (1.5 to 2 years old) Labrador Retrievers (8 males and 4 females; mean ± SD body weight, 27 ± 1.6 kg). PROCEDURES Each dog received 2 bolus injections of sulfur hexafluoride during CEUS. Three small oval ROIs (area of each ROI, 0.11 cm(2)) located in a row with a distance of 1 mm between adjacent ROIs and 1 large oval ROI (area, 1 cm(2)) that encompassed the 3 smaller ROIs were manually drawn in the renal cortex. The ROIs were located at a depth of 1.5 to 2.0 cm in the near field of the renal cortex. Software analysis of time-intensity curves within each ROI was used to identify peak enhancement, time to peak enhancement, regional blood flow, and mean transit time. RESULTS The location and size of the ROIs of unsedated dogs did not cause significant differences in the mean values of the renal perfusion variables. CONCLUSIONS AND CLINICAL RELEVANCE The development of CEUS has provided a unique means for visually examining and quantifying tissue perfusion. Results of this study indicated that it was possible to use small or large ROIs during renal CEUS to evaluate renal perfusion in dogs. PMID:27463550

  3. [Renal elastography].

    PubMed

    Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

    2016-04-01

    Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. PMID:26976058

  4. Models of Spectral Galaxy Evolution including the effects of Dust

    NASA Astrophysics Data System (ADS)

    Möller, C. S.; Fritze-v. Alvensleben, U.; Fricke, K. J.

    To analyse the effects of dust to the UV emission in various galaxy types we present our evolutionary synthesis models which includes dust absorption in a chemically consistent way. The time and redshift evolution of the extinction is based on the evolution of the gas content and metallicity. Comparing our model SED's with templates from Kennicutt's and Kinney et al.'s atlas we show the detailed agreement with integrated spectra of galaxies and point out the importance of aperture effects. We are able to predict the UV fluxes for different galaxy types. Combined with a cosmological model we show the differences in the evolutionary and k-corrections comparing models with and without dust.

  5. The correlation between effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with renal scintigraphy 99mTc-DTPA study

    NASA Astrophysics Data System (ADS)

    Ratnasari, D.; Nazir, F.; Toresano, L. O. H. Z.; Pawiro, S. A.; Soejoko, D. S.

    2016-03-01

    The prevalence of chronic renal diseases in Indonesia has an increasing annual trend, because it is frequently unrecognized and often co-exists with other disease. GFR and ERPF are parameters currently utilized to estimate renal function at routine renal scintigraphy 99m-Tc DTPA study. This study used 99m-Tc DTPA to measure GFR and ERPF. The purpose of this study was to find the correlation between ERPF and GFR, for ERPF analysis with Schlegel's method, and GFR analysis with Gate's method, as well as to find correction factor between both variables. Analysis of renal scintigraphy has been performed at Department of Nuclear Medicine Pertamina Center Hospital to thirty patient images acquired from 2014 to 2015 which were analyzed retrospectively data, using gamma camera dual head with counting method from renal scintigraphy 99m-Tc DTPA study. The calculation was executed by means of both display and manual calculation. Pearson's statistical analysis resulted on Positive Correlation for all data, with ERPF and GFR (display) showing Strongly Positive Correlation (r = 0.82; p- value < 0.05). Standard deviation was found to be 27.58 and 107.64 for GFR and ERPF (display), respectively. Our result indicated that the use of 99mTc-DTPA measure ERPF was not recommended.

  6. In Brief: Evolution teacher survey; Effects of drought on rainforest

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2005-05-01

    More than 30% of teachers responding to an informal survey indicated that they feel pressured to include creationism, intelligent design, or other nonscientific alternatives to evolution in their science classrooms. An experiment to simulate the effects of climate change and severe drought on a parcel of rainforest in the Brazilian Amazon has found that some parts of the affected forest tolerated the dry condition by absorbing water from deeper in the soil.

  7. Calcium transport in canine renal basolateral membrane vesicles. Effects of parathyroid hormone.

    PubMed Central

    Scoble, J E; Mills, S; Hruska, K A

    1985-01-01

    The effects of parathyroid hormone were studied on Ca2+ fluxes in canine renal proximal tubular basolateral membrane vesicles (BLMV). Efflux of Ca2+ from preloaded BLMV was found to be stimulated by an external Na+ gradient, and this was inhibited by the Na+ ionophore, monensin, and enhanced by intravesicular negative electrical potentials, which indicated electrogenic Na+/Ca2+ exchange activity. There was a Na+ gradient independent Ca2+ flux, but membrane binding of Ca2+ was excluded from contributing to the Na+ gradient-dependent efflux. The Na+ gradient-dependent flux of Ca2+ was very rapid, and even 2- and 5-s points may not fully represent absolute initial rates. It was saturable with respect to the interaction of Ca2+ and Na+ with an apparent (5 s) Km for Na+-dependent Ca2+ uptake of 10 microM, and an apparent (5 s) Vmax of 0.33 nmol/mg protein per 5 s. The Na+ concentration that yielded half maximal Ca2+ efflux (2 s) was 11 mM, and the Hill coefficient was two or greater. Both Na+ gradient dependent and independent Ca2+ efflux were decreased in BLMV prepared from kidneys of thyroparathyroidectomized (TPTX) dogs, and both were stimulated by parathyroid hormone (PTH) infusion to TPTX dogs. BLMV from TPTX dogs exhibited significantly reduced maximal stimulation of Na+ gradient-dependent Ca2+ uptake with an apparent (5 s) Vmax of 0.23 nmol/mg protein per 5 s, but the apparent Km was 8 microM, which was unchanged from normal. The Na+ gradient independent Ca2+ uptake was also reduced in BLMV from TPTX dogs compared with normal. Thus, PTH stimulated both Na+/Ca2+ exchange activity and Na+ independent Ca2+ flux. In vivo, the latter could result in an elevation of cytosolic Ca2+ by PTH, and this might contribute to the observed decrease in solute transport in the proximal tubule. Images PMID:3988932

  8. Studies of the effects of FK506 on renal allografting in the beagle dog.

    PubMed

    Ochiai, T; Nagata, M; Nakajima, K; Suzuki, T; Sakamoto, K; Enomoto, K; Gunji, Y; Uematsu, T; Goto, T; Hori, S

    1987-12-01

    The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaensis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2-3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects. PMID:2447688

  9. Anti-Diabetic and Hepato-Renal Protective Effects of Ziyuglycoside II Methyl Ester in Type 2 Diabetic Mice

    PubMed Central

    Son, Dong Ju; Hwang, Seock Yeon; Kim, Myung-Hyun; Park, Un Kyu; Kim, Byoung Soo

    2015-01-01

    Type 2 diabetes is a metabolic disorder caused by abnormal carbohydrate metabolism, and closely associated with abnormal lipid metabolism and hepato-renal dysfunction. This study investigated the anti-diabetic and hepato-renal protective properties of ziyuglycoside I (ZG01) derivative on type 2 diabetes. ZG01 was isolated from roots of Sanguisorba officinalis and chemically modified by deglycosylation and esterification to obtained ziyuglycoside II methyl ester (ZG02-ME). Here, we showed that ZG02-ME has stronger anti-diabetic activity than the original compound (ZG01) through decreasing blood glucose, glycated hemoglobin (HbA1c), and insulin levels in a mouse model of type 2 diabetes (db/db mice). We further found that ZG02-ME treatment effectively ameliorated serum insulin, leptin and C-peptide levels, which are key metabolic hormones, in db/db mice. In addition, we showed that elevated basal blood lipid levels were decreased by ZG02-ME treatment in db/db mice. Furthermore, treatment of ZG02-ME significantly decreased serum AST, ALT, BUN, creatinine, and liver lipid peroxidation in db/db mice. These results demonstrated that compared to ZG01, chemically modified ZG02-ME possess improved anti-diabetic properties, and has hepato-renal protective activities in type 2 diabetes. PMID:26198246

  10. Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy

    PubMed Central

    Kim, Bo Hwan; Lee, Eun Soo; Choi, Ran; Nawaboot, Jarinyaporn; Lee, Mi Young; Lee, Eun Young; Kim, Hyeon Soo

    2016-01-01

    Purpose Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. Materials and Methods Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. Results Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. Conclusion Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway. PMID:26996567

  11. Morphological and cytohistochemical evaluation of renal effects of cadmium-doped silica nanoparticles given intratracheally to rat

    NASA Astrophysics Data System (ADS)

    Coccini, T.; Roda, E.; Barni, S.; Manzo, L.

    2013-04-01

    Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.

  12. The Preventive Effects of Diminazene Aceturate in Renal Ischemia/Reperfusion Injury in Male and Female Rats

    PubMed Central

    2014-01-01

    Background. Angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor (ACE2/Ang-1-7/MasR) appears to counteract most of the deleterious actions of angiotensin-converting enzyme/angiotensin II/angiotensin II receptor 1 (ACE/Ang II/AT1R) in renal ischemia/reperfusion (I/R) injury but ACE2 activity and its levels are sexually dimorphic in the kidney. This study was designed to evaluate the effects of activation endogenous ACE2 using the diminazene aceturate (DIZE) in renal I/R injury in male and female rats. Methods. 36 Wistar rats were divided into two groups of male and female and each group distinct to three subgroups (n = 6). I/R group was subjected to 45 min of bilateral ischemia and 24 h of reperfusion, while treatment group received DIZE (15 mg/kg/day) for three days before the induction of I/R. The other group was assigned as the sham-operated group. Results. DIZE treatment in male rats caused a significant decrease in blood urea nitrogen (BUN), creatinine, liver functional indices, serum malondialdehyde (MDA), and increase kidney nitrite levels (P < 0.05), and in female rats a significant increase in creatinine and decrease serum nitrite levels compared to the I/R group (P < 0.05). Conclusions. DIZE may protect the male kidney from renal I/RI through antioxidant activity and elevation of circulating nitrite level. PMID:25478235

  13. Anti-Diabetic and Hepato-Renal Protective Effects of Ziyuglycoside II Methyl Ester in Type 2 Diabetic Mice.

    PubMed

    Son, Dong Ju; Hwang, Seock Yeon; Kim, Myung-Hyun; Park, Un Kyu; Kim, Byoung Soo

    2015-07-01

    Type 2 diabetes is a metabolic disorder caused by abnormal carbohydrate metabolism, and closely associated with abnormal lipid metabolism and hepato-renal dysfunction. This study investigated the anti-diabetic and hepato-renal protective properties of ziyuglycoside I (ZG01) derivative on type 2 diabetes. ZG01 was isolated from roots of Sanguisorba officinalis and chemically modified by deglycosylation and esterification to obtained ziyuglycoside II methyl ester (ZG02-ME). Here, we showed that ZG02-ME has stronger anti-diabetic activity than the original compound (ZG01) through decreasing blood glucose, glycated hemoglobin (HbA1c), and insulin levels in a mouse model of type 2 diabetes (db/db mice). We further found that ZG02-ME treatment effectively ameliorated serum insulin, leptin and C-peptide levels, which are key metabolic hormones, in db/db mice. In addition, we showed that elevated basal blood lipid levels were decreased by ZG02-ME treatment in db/db mice. Furthermore, treatment of ZG02-ME significantly decreased serum AST, ALT, BUN, creatinine, and liver lipid peroxidation in db/db mice. These results demonstrated that compared to ZG01, chemically modified ZG02-ME possess improved anti-diabetic properties, and has hepato-renal protective activities in type 2 diabetes. PMID:26198246

  14. Effects of pretransplant plasmapheresis and rituximab on recurrence of focal segmental glomerulosclerosis in adult renal transplant recipients

    PubMed Central

    Park, Hoon Suk; Hong, Yuah; Sun, In O; Chung, Byung Ha; Kim, Hyung Wook; Choi, Bum Soon; Park, Cheol Whee; Jin, Dong Chan; Kim, Yong Soo

    2014-01-01

    Background/Aims Recurrent focal segmental glomerulosclerosis (FSGS) following renal transplantation is relatively common. However, the risk factors and optimal pretransplant treatment preventing recurrence of FSGS remain controversial. Methods We retrospectively reviewed 27 adult renal transplant recipients with FSGS over a period of 10 years. We first compared possible risk factors for FSGS recurrence between the recurrence and nonrecurrence groups. Then we evaluated the effect of pretransplant plasmapheresis (PP; n = 4) and PP with rituximab (PP + RTX; n = 5) on recurrence of FSGS after transplantation compared to control patients that were not treated with these modalities. Results There were seven recurrences in 27 patients (25.9%), but there were no significant differences in possible risk factors for FSGS recurrence between the two groups. Recurrence rates between patients with pretransplant PP or PP + RTX and control patients were not significantly different (22.2% vs. 27.7%, p > 0.05). There was also no significant difference in recurrence between the pretransplant PP and PP + RTX groups (25% vs. 20%, p > 0.05). Conclusions Pretransplant PP or PP + RTX do not significantly decrease the recurrence of FSGS in adult renal transplant candidates. PMID:25045296

  15. Comparative effect of propofol versus sevoflurane on renal ischemia/reperfusion injury after elective open abdominal aortic aneurysm repair

    PubMed Central

    Ammar, AS; Mahmoud, KM

    2016-01-01

    Background: Renal injury is a common cause of morbidity and mortality after elective abdominal aortic aneurysm (AAA) repair. Propofol has been reported to protect several organs from ischemia/reperfusion (I/R) induced injury. We performed a randomized clinical trial to compare propofol and sevoflurane for their effects on renal I/R injury in patients undergoing elective AAA repair. Materials and Methods: Fifty patients scheduled for elective AAA repair were randomized to receive propofol anesthesia in group I or sevoflurane anesthesia in group II. Urinary specific kidney proteins (N-acetyl-beta-glucosamidase, alpha-1-microglobulin, glutathione transferase [GST]-pi, GST-alpha) were measured within 5 min of starting anesthesia as a base line (T0), at the end of surgery (T1), 8 h after surgery (T2), 16 h after surgery (T3), and 24 h postoperatively (T4). Serum pro-inflammatory cytokines (tumor necrosis factor-α and interleukin 1-β) were measured at the same time points. In addition, serum creatinine and cystatin C were measured before starting surgery as a baseline and at days 1, 3, and 6 after surgery. Results: Postoperative urinary concentrations of all measured kidney specific proteins and serum pro-inflammatory cytokines were significantly lower in the propofol group. In addition, the serum creatinine and cystatin C were significantly lower in the propofol group compared with the sevoflurane group. Conclusion: Propofol significantly reduced renal injury after elective open AAA repair and this could have clinical implications in situations of expected renal I/R injury. PMID:27375385

  16. Effects of lornoxicam and intravenous ibuprofen on erythrocyte deformability and hepatic and renal blood flow in rats

    PubMed Central

    Arpacı, Hande; Çomu, Faruk Metin; Küçük, Ayşegül; Kösem, Bahadır; Kartal, Seyfi; Şıvgın, Volkan; Turgut, Hüseyin Cihad; Aydın, Muhammed Enes; Koç, Derya Sebile; Arslan, Mustafa

    2016-01-01

    Background Change in blood supply is held responsible for anesthesia-related abnormal tissue and organ perfusion. Decreased erythrocyte deformability and increased aggregation may be detected after surgery performed under general anesthesia. It was shown that nonsteroidal anti-inflammatory drugs decrease erythrocyte deformability. Lornoxicam and/or intravenous (iv) ibuprofen are commonly preferred analgesic agents for postoperative pain management. In this study, we aimed to investigate the effects of lornoxicam (2 mg/kg, iv) and ibuprofen (30 mg/kg, iv) on erythrocyte deformability, as well as hepatic and renal blood flows, in male rats. Methods Eighteen male Wistar albino rats were randomly divided into three groups as follows: iv lornoxicam-treated group (Group L), iv ibuprofen-treated group (Group İ), and control group (Group C). Drug administration was carried out by the iv route in all groups except Group C. Hepatic and renal blood flows were studied by laser Doppler, and euthanasia was performed via intra-abdominal blood uptake. Erythrocyte deformability was measured using a constant-flow filtrometry system. Results Lornoxicam and ibuprofen increased the relative resistance, which is an indicator of erythrocyte deformability, of rats (P=0.016). Comparison of the results from Group L and Group I revealed no statistically significant differences (P=0.694), although the erythrocyte deformability levels in Group L and Group I were statistically higher than the results observed in Group C (P=0.018 and P=0.008, respectively). Hepatic and renal blood flows were significantly lower than the same in Group C. Conclusion We believe that lornoxicam and ibuprofen may lead to functional disorders related to renal and liver tissue perfusion secondary to both decreased blood flow and erythrocyte deformability. Further studies regarding these issues are thought to be essential. PMID:27536068

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

    PubMed

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

    2016-02-01

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

  18. Dental management of people with renal disease and renal transplants.

    PubMed

    Ferguson, C A; Whyman, R A

    1998-09-01

    Chronic renal failure is the result of progressive loss of functioning nephrons leading to loss of renal function and accumulation of excretory products. Loss of the regulatory and excretory functions of the kidneys causes oral manifestations and multiple complications which have implications for dental care. Dental management of patients with renal failure and renal transplants involves consideration of specific haematological and cardiovascular effects, and implications for the prescribing and use of pharmaceuticals. It also requires the dentist to appreciate the potential for involvement of multiple organ systems in the disease process and the implications this has for dental care. The orofacial manifestations of chronic renal failure are secondary to systemic manifestations and are not specific to the diagnosis of end-stage renal disease. PMID:9775650

  19. Acute and long-term renal and metabolic effects of piretanide in congestive cardiac failure.

    PubMed Central

    McNabb, W R; Noormohamed, F H; Lant, A F

    1988-01-01

    1. The renal and metabolic effects of the sulphamoylbenzoic acid diuretic, piretanide, have been studied, under controlled dietary conditions, in 39 patients with congestive cardiac failure. 2. In acute studies, peak saluresis occurred within 4 h of oral piretanide administration; saluresis was complete within 6 h, after which a significant antidiuretic effect was observed. Addition of triamterene, 50 mg, blunted the 0-6 h kaliuretic effect of piretanide. Over 24 h, piretanide, alone, caused insignificant urinary losses of potassium when compared with control. 3. In comparative studies, the piretanide dose-response curve was found to be parallel to that of frusemide over the dose range studied. The 0-6 h saluretic responses of piretanide, 6, 12 and 18 mg, were found to be equivalent to frusemide, 40, 80 and 120 mg respectively. The collective mean ratios of all the saluretic responses to each dose of piretanide with the corresponding dose of frusemide was observed to be 0.99 +/- 0.12, over 0-6 h period, and 0.86 +/- 0.09 over the 24 h period. The relative potency of piretanide, when compared with frusemide was found to be 6.18 (95% confidence limits 4.87-8.33), over the 0-6 h period, and 4.73 (95% confidence limits 3.65-6.14), over 24 h period. 4. In 15 patients in severe cardiac failure, urinary recovery of piretanide, over first 6 h, at the start of treatment was 21.2 +/- 2.1% while efficiency of the diuretic (mmol Na/mg drug) was 47.3 +/- 4.1. Long-term piretanide therapy was continued in the same group for up to and in some cases over 3 years. No other diuretics or potassium supplements were given. Piretanide dosage ranged from 6 to 24 mg day-1 according to clinical need. Plasma potassium fell significantly at 12 and 24 months, though remaining within the normal range. At these same times, significant elevations in both plasma urate and total fasting cholesterol were observed. Two patients developed overt gout on high dose piretanide therapy (24 mg day-1

  20. Sodium-Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport: From Bench to Bedside.

    PubMed

    Mudaliar, Sunder; Polidori, David; Zambrowicz, Brian; Henry, Robert R

    2015-12-01

    Type 2 diabetes is a chronic disease with disabling micro- and macrovascular complications that lead to excessive morbidity and premature mortality. It affects hundreds of millions of people and imposes an undue economic burden on populations across the world. Although insulin resistance and insulin secretory defects play a major role in the pathogenesis of hyperglycemia, several other metabolic defects contribute to the initiation/worsening of the diabetic state. Prominent among these is increased renal glucose reabsorption, which is maladaptive in patients with diabetes. Instead of an increase in renal glucose excretion, which could ameliorate hyperglycemia, there is an increase in renal glucose reabsorption, which helps sustain hyperglycemia in patients with diabetes. The sodium-glucose cotransporter (SGLT) 2 inhibitors are novel antidiabetes agents that inhibit renal glucose reabsorption and promote glucosuria, thereby leading to reductions in plasma glucose concentrations. In this article, we review the long journey from the discovery of the glucosuric agent phlorizin in the bark of the apple tree through the animal and human studies that led to the development of the current generation of SGLT2 inhibitors. PMID:26604280

  1. Protective effects of quercetin and hyperoside on renal fibrosis in rats with unilateral ureteral obstruction

    PubMed Central

    YAN, YANG; FENG, YUAN; LI, WEI; CHE, JIAN-PING; WANG, GUANG-CHUN; LIU, MIN; ZHENG, JUN-HUA

    2014-01-01

    Prevention of renal fibrosis is an important therapeutic strategy in the treatment of obstructive nephropathy. The purpose of the present study was to identify whether the combination of two natural plant-derived flavanoids, quercetin and hyperoside (QH), could inhibit renal fibrosis in the model of unilateral ureteral obstruction (UUO) in rats. QH mixtures (1:1) were fed to Wistar rats, and UUO ligation was performed on all the rats with the exception of the sham group. Masson’s trichrome staining was used for interstitial fibrosis, while immunohistochemistry and western blot analysis were used to detect the expression of α-smooth muscle actin (SMA) and fibronectin (FN). In the QH group, the expression of SMA and FN was significantly lower than that in the untreated UUO group. In addition, QH administration significantly inhibited the SMA and FN expression of mesangial cells induced by interleukin-1β. Consequently, it was evident that combinational QH therapy prevented UUO-induced renal fibrosis. Based on these findings, the combinatorial intervention of phytomedicine may present an improved treatment strategy for renal fibrotic disease. PMID:25120589

  2. Radiation Recoil Effects on the Dynamical Evolution of Asteroids

    NASA Astrophysics Data System (ADS)

    Cotto-Figueroa, Desiree

    The Yarkovsky effect is a radiation recoil force that results in a semimajor axis drift in the orbit that can cause Main Belt asteroids to be delivered to powerful resonances from which they could be transported to Earth-crossing orbits. This force depends on the spin state of the object, which is modified by the YORP effect, a variation of the Yarkovsky effect that results in a torque that changes the spin rate and the obliquity. Extensive analyses of the basic behavior of the YORP effect have been previously conducted in the context of the classical spin state evolution of rigid bodies (YORP cycle). However, the YORP effect has an extreme sensitivity to the topography of the asteroids and a minor change in the shape of an aggregate asteroid can stochastically change the YORP torques. Here we present the results of the first simulations that self-consistently model the YORP effect on the spin states of dynamically evolving aggregates. For these simulations we have developed several algorithms and combined them with two codes, TACO and pkdgrav. TACO is a thermophysical asteroid code that models the surface of an asteroid using a triangular facet representation and which can compute the YORP torques. The code pkdgrav is a cosmological N-body tree code modified to simulate the dynamical evolution of asteroids represented as aggregates of spheres using gravity and collisions. The continuous changes in the shape of an aggregate result in a different evolution of the YORP torques and therefore aggregates do not evolve through the YORP cycle as a rigid body would. Instead of having a spin evolution ruled by long periods of rotational acceleration and deceleration as predicted by the classical YORP cycle, the YORP effect is self-limiting and stochastic on aggregate asteroids. We provide a statistical description of the spin state evolution which lays out the foundation for new simulations of a coupled Yarkovsky/YORP evolution. Both self-limiting YORP and to a lesser

  3. New chemical evolution analytical solutions including environment effects

    NASA Astrophysics Data System (ADS)

    Spitoni, E.

    2015-07-01

    In the last years, more and more interest has been devoted to analytical solutions, including inflow and outflow, to study the metallicity enrichment in galaxies. In this framework, we assume a star formation rate which follows a linear Schmidt law, and we present new analytical solutions for the evolution of the metallicity (Z) in galaxies. In particular, we take into account environmental effects including primordial and enriched gas infall, outflow, different star formation efficiencies and galactic fountains. The enriched infall is included to take into account galaxy-galaxy interactions. Our main results can be summarized as: (i) when a linear Schmidt law of star formation is assumed, the resulting time evolution of the metallicity Z is the same either for a closed-box model or for an outflow model. (ii) The mass-metallicity relation for galaxies which suffer a chemically enriched infall, originating from another evolved galaxy with no pre-enriched gas, is shifted down in parallel at lower Z values, if compared to the closed box model. (iii) When a galaxy suffers at the same time a primordial infall and a chemically enriched one, the primordial infall always dominates the chemical evolution. (iv) We present new solutions for the metallicity evolution in a galaxy which suffers galactic fountains and an enriched infall from another galaxy at the same time. The analytical solutions presented here can be very important to study the metallicity (oxygen), which is measured in high-redshift objects. These solutions can be very useful: (a) in the context of cosmological semi-analytical models for galaxy formation and evolution, and (b) for the study of compact groups of galaxies.

  4. Effects of a Renal Rehabilitation Exercise Program in Patients with CKD: A Randomized, Controlled Trial

    PubMed Central

    Rossi, Ana P.; Burris, Debra D.; Lucas, F. Leslie; Crocker, Gail A.

    2014-01-01

    Background and objectives Patients with CKD have a high prevalence of cardiovascular disease associated with or exacerbated by inactivity. This randomized, controlled study investigated whether a renal rehabilitation exercise program for patients with stages 3 or 4 CKD would improve their physical function and quality of life. Design, setting, participants, & measurements In total, 119 adults with CKD stages 3 and 4 were randomized, and 107 of these patients proceeded to usual care or the renal rehabilitation exercise intervention consisting of usual care plus guided exercise two times per week for 12 weeks (24 sessions). Physical function was determined by three well established performance-based tests: 6-minute walk test, sit-to-stand test, and gait-speed test. Health-related quality of life was assessed by the RAND 36-Item Short Form Health Survey. Results At baseline, no differences in self-reported level of activity, 6-minute walk test, and sit-to-stand test scores were observed between the usual care (n=48) and renal rehabilitation exercise (n=59) groups, although baseline gait-speed test score was higher in the renal rehabilitation exercise group (P<0.001). At follow-up, the renal rehabilitation exercise group but not the usual care group showed significant improvements in the 6-minute walk test (+210.4±266.0 ft [19% improvement] versus −10±219.9 ft; P<0.001), the sit-to-stand test (+26.9±27% of age prediction [29% improvement] versus +0.7±12.1% of age prediction; P<0.001), and the RAND-36 physical measures of role functioning (P<0.01), physical functioning (P<0.01), energy/fatigue levels (P=0.01), and general health (P=0.03) and mental measure of pain scale (P=0.04). The renal rehabilitation exercise regimen was generally well tolerated. Conclusions A 12-week/24-session renal rehabilitation exercise program improved physical capacity and quality of life in patients with CKD stages 3 and 4. Longer follow-up is needed to determine if these findings will

  5. Prolonged urocortin 2 administration in experimental heart failure: sustained hemodynamic, endocrine, and renal effects.

    PubMed

    Rademaker, Miriam T; Charles, Christopher J; Ellmers, Leigh J; Lewis, Lynley K; Nicholls, M Gary; Richards, A Mark

    2011-06-01

    Although acute administration of urocortin 2 has beneficial actions in heart failure, the integrated hemodynamic, hormonal, and renal effects of sustained urocortin 2 treatment in this disease have not been investigated. In the current study, we administered a 4-day infusion of a vehicle control (0.9% saline; n=6) or urocortin 2 (0.75 μg/kg per hour; n=6) to sheep with pacing-induced heart failure. Compared with time-matched controls, infusion of urocortin 2 produced rapid (30-minute) and persistent (4-day) improvements in cardiac contractility (day 4: control 905±73 versus urocortin 2 1424±158 mm Hg/s; P<0.001) and output (2.6±0.1 versus 3.8±0.3 L/min; P<0.001), together with reductions in left atrial pressure (28±1 versus 12±1 mm Hg; P<0.001) and peripheral resistance (30±2 versus 20±2 mm Hg/L per min; P<0.001). In contrast, urocortin 2-induced falls in mean arterial pressure were not established until the second day (day 4: 74±2 versus 72±2 mm Hg; P<0.05). Prolonged urocortin 2 administration was associated with sustained (days 0 to 4) declines in plasma renin activity (day 4: 1.33±0.27 versus 0.73±0.20 nmol/L per hour; P<0.001), aldosterone (970±383 versus 396±96 pmol/L; P<0.05), vasopressin (2.4±0.8 versus 1.3±0.1 pmol/L; P<0.05), endothelin 1 (7.2±0.7 versus 4.5±0.4 pmol/L; P<0.01), and atrial (269±27 versus 150±19 pmol/L; P<0.001) and B-type (65±9 versus 29±6 pmol/L; P<0.001) natriuretic peptides, as well as an acute transient rise in plasma cortisol (day 1: P<0.001). Chronic urocortin 2 also persistently augmented urinary sodium (day 4: 4-fold increase; P<0.001) and creatinine (1.4-fold; P<0.001) excretion and creatinine clearance (1.5-fold; P<0.01) compared with control. Food consumption was temporarily suppressed (P<0.05). In conclusion, 4-day urocortin 2 administration induces sustained improvements in hemodynamics and renal function, in association with inhibition of multiple vasoconstrictor/volume-retaining systems. These

  6. Effects of low-molecular-weight-chitosan on the adenine-induced chronic renal failure rats in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Zhi, Xuan; Han, Baoqin; Sui, Xianxian; Hu, Rui; Liu, Wanshun

    2015-02-01

    The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37° for 24 h to obtain LMWC. In vitro, the effect of LMWC on the proliferation of renal tubular epithelial cells (RTEC) showed that it had no cytotoxic effect and could promote cell growth. For the in vivo experiment, chronic renal failure rats induced by adenine were randomly divided into control group, Niaoduqing group, and high-, medium- and low-dose LMWC groups. For each group, we detected serum creatinine (SCR), blood urea nitrogen (BUN), and total superoxide dismutase (T-SOD), glutathione oxidase (GSH-Px) activities of renal tissue, and obtained the ratio of kidney weight/body weight, pathological changes of kidney. The levels of serum SCR, BUN were higher in the adenine-induced rats than those in the control group, indicating that the rat chronic renal failure model worked successfully. The results after treatment showed that LMWC could reduce the SCR and BUN levels and enhance the activities/levels of T-SOD and GSH-PX in kidney compared to control group. Histopathological examination revealed that adenine-induced renal alterations were restored by LMWC at three tested dosages, especially at the low dosage of 100 mg kg-1 d-1.

  7. Association between occupational exposure to arsenic and neurological, respiratory and renal effects

    SciTech Connect

    Halatek, Tadeusz Sinczuk-Walczak, Halina; Rabieh, Sasan; Wasowicz, Wojciech

    2009-09-01

    Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n = 16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and {beta}{sub 2}-microglobulin ({beta}{sub 2}M) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m{sup 3}). The contents of lead did not exceed the TLV (0.05 mg/m{sup 3}). Low CC16 levels in serum (12.1 {mu}g/l) of workers with SNS and VEP symptoms and highest level As-U (x{sub a} 39.0 {mu}g/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum {beta}{sub 2}M and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system.

  8. Drug-induced renal disorders.

    PubMed

    Ghane Shahrbaf, Fatemeh; Assadi, Farahnak

    2015-01-01

    Drug-induced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acid-base and fluid electrolytes disorders. Certain drugs can cause alteration in intraglomerular hemodynamics, inflammatory changes in renal tubular cells, leading to acute kidney injury (AKI), tubulointerstitial disease and renal scarring. Drug-induced nephrotoxicity tends to occur more frequently in patients with intravascular volume depletion, diabetes, congestive heart failure, chronic kidney disease, and sepsis. Therefore, early detection of drugs adverse effects is important to prevent progression to end-stage renal disease. Preventive measures requires knowledge of mechanisms of drug-induced nephrotoxicity, understanding patients and drug-related risk factors coupled with therapeutic intervention by correcting risk factors, assessing baseline renal function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations. PMID:26468475

  9. Modelling evolution of asteroid's rotation due to the YORP effect

    NASA Astrophysics Data System (ADS)

    Golubov, Oleksiy; Lipatova, Veronika; Scheeres, Daniel J.

    2016-05-01

    The Yarkovsky--O'Keefe--Radzievskii--Paddack (or YORP) effect is influence of light pressure on rotation of asteroids. It is the most important factor for evolution of rotation state of small asteroids, which can drastically alter their rotation rate and obliquity over cosmologic timescales.In the poster we present our program, which calculates evolution of ratation state of small asteroids subject to the YORP effect. The program accounts for both axial and obliquity components of YORP, takes into account the thermal inertia of the asteroid's soil, and the tangential YORP. The axial component of YORP is computed using the model by Steinberg and Sari (AJ, 141, 55). The thermal inertia is accounted for in the framework of Golubov et al. 2016 (MNRAS, stw540). Computation of the tangential YORP is based on a siple analytical model, whose applicability is verified via comparison to exact numeric simulations.We apply the program to different shape models of asteroids, and study coupled evolution of their rotation rate and obliquity.

  10. Parental effects in ecology and evolution: mechanisms, processes and implications

    PubMed Central

    Badyaev, Alexander V.; Uller, Tobias

    2009-01-01

    As is the case with any metaphor, parental effects mean different things to different biologists—from developmental induction of novel phenotypic variation to an evolved adaptation, and from epigenetic transference of essential developmental resources to a stage of inheritance and ecological succession. Such a diversity of perspectives illustrates the composite nature of parental effects that, depending on the stage of their expression and whether they are considered a pattern or a process, combine the elements of developmental induction, homeostasis, natural selection, epigenetic inheritance and historical persistence. Here, we suggest that by emphasizing the complexity of causes and influences in developmental systems and by making explicit the links between development, natural selection and inheritance, the study of parental effects enables deeper understanding of developmental dynamics of life cycles and provides a unique opportunity to explicitly integrate development and evolution. We highlight these perspectives by placing parental effects in a wider evolutionary framework and suggest that far from being only an evolved static outcome of natural selection, a distinct channel of transmission between parents and offspring, or a statistical abstraction, parental effects on development enable evolution by natural selection by reliably transferring developmental resources needed to reconstruct, maintain and modify genetically inherited components of the phenotype. The view of parental effects as an essential and dynamic part of an evolutionary continuum unifies mechanisms behind the origination, modification and historical persistence of organismal form and function, and thus brings us closer to a more realistic understanding of life's complexity and diversity. PMID:19324619

  11. Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure

    PubMed Central

    Konkalmatt, Prasad R.; Asico, Laureano D.; Zhang, Yanrong; Yang, Yu; Drachenberg, Cinthia; Zheng, Xiaoxu; Han, Fei; Jose, Pedro A.; Armando, Ines

    2016-01-01

    Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing of Drd2 using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue of Drd2 expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vector with DRD2. Renal Drd2 siRNA treatment decreased the renal expression of DRD2 protein by 55%, and DRD2 AAV treatment increased the renal expression of DRD2 protein by 7.5- to 10-fold. Renal-selective DRD2 rescue reduced the expression of proinflammatory factors and kidney injury, preserved renal function, and normalized systolic and diastolic blood pressure. These results demonstrate that the deleterious effects of renal-selective Drd2 silencing on renal function and blood pressure were rescued by renal-selective overexpression of DRD2. Moreover, the deleterious effects of 45-minute bilateral ischemia/reperfusion on renal function and blood pressure in mice were ameliorated by a renal-selective increase in DRD2 expression by the retrograde ureteral infusion of DRD2 AAV immediately after the induction of ischemia/reperfusion injury. Thus, 14 days after ischemia/reperfusion injury, the renal expression of profibrotic factors, serum creatinine, and blood pressure were lower in mice infused with DRD2 AAV than in those infused with control AAV. These results indicate an important role of renal DRD2 in limiting renal injury and preserving normal renal function and blood pressure. PMID:27358912

  12. Effects of electron temperature anisotropy on proton mirror instability evolution

    NASA Astrophysics Data System (ADS)

    Ahmadi, Narges; Germaschewski, Kai; Raeder, Joachim

    2016-06-01

    Proton mirror modes are large amplitude nonpropagating structures frequently observed in the magnetosheath. It has been suggested that electron temperature anisotropy can enhance the proton mirror instability growth rate while leaving the proton cyclotron instability largely unaffected, therefore causing the proton mirror instability to dominate the proton cyclotron instability in Earth's magnetosheath. Here we use particle-in-cell simulations to investigate the electron temperature anisotropy effects on proton mirror instability evolution. Contrary to the hypothesis, electron temperature anisotropy leads to excitement of the electron whistler instability. Our results show that the electron whistler instability grows much faster than the proton mirror instability and quickly consumes the electron-free energy so that there is no electron temperature anisotropy left to significantly impact the evolution of the proton mirror instability.

  13. Strain rate effects on soot evolution in turbulent nonpremixed flames

    NASA Astrophysics Data System (ADS)

    Lew, Jeffry K.; Mueller, Michael E.; Mahmoud, Saleh; Alwahabi, Zeyad T.; Dally, Bassam B.; Nathan, Graham J.

    2015-11-01

    Large Eddy Simulations (LES) of turbulent nonpremixed ethylene/hydrogen/nitrogen (2/2/1 by volume) jet flames are conducted to investigate the effects of global strain rate on soot evolution. The exit strain rate is varied by fixing the Reynolds number as the burner diameter and exit velocity are altered. A detailed integrated LES approach is employed that includes a nonpremixed flamelet model that accounts for heat losses from radiation, a transport equation model to account for unsteadiness in polycyclic aromatic hydrocarbon (PAH) evolution, a detailed soot model based on the Hybrid Method of Moments, and a novel presumed subfilter PDF model for soot-turbulence interactions. As the strain rate increases, the maximum soot volume fraction decreases due to the suppression of PAH formation. This trend with increasing strain rate is validated against experimental measurements conducted at The University of Adelaide.

  14. Magnetic field effects on plant growth, development, and evolution

    PubMed Central

    Maffei, Massimo E.

    2014-01-01

    The geomagnetic field (GMF) is a natural component of our environment. Plants, which are known to sense different wavelengths of light, respond to gravity, react to touch and electrical signaling, cannot escape the effect of GMF. While phototropism, gravitropism, and tigmotropism have been thoroughly studied, the impact of GMF on plant growth and development is not well-understood. This review describes the effects of altering magnetic field (MF) conditions on plants by considering plant responses to MF values either lower or higher than those of the GMF. The possible role of GMF on plant evolution and the nature of the magnetoreceptor is also discussed. PMID:25237317

  15. Congenital Seminal Vesicle Cyst and Ipsilateral Renal Agenesis (Zinner Syndrome): A Rare Association and Its Evolution from Early Childhood to Adolescence

    PubMed Central

    Kanavaki, Aikaterini; Vidal, Isabelle; Merlini, Laura; Hanquinet, Sylviane

    2015-01-01

    Zinner syndrome, the association of congenital seminal vesicle cyst and ipsilateral renal agenesis, is more often reported in adults or older adolescents. We present a case of a boy, followed up in our hospital since birth for right renal agenesis who at the age of 4 years presented a right paravesical cyst on ultrasound. The cyst was initially considered as an ureterocele. The diagnosis of Zinner syndrome was made later, at the age of 15 years by ultrasound and magnetic resonance imaging; at that moment the cyst had increased in size and had changed in aspect. This malformation should be considered in the differential diagnosis of a pelvic cyst in male patients with renal agenesis. PMID:26788458

  16. Congenital ureteropelvic junction obstruction: physiopathology, decoupling of tout court pelvic dilatation-obstruction semantic connection, biomarkers to predict renal damage evolution.

    PubMed

    Alberti, C

    2012-02-01

    The widespread use of fetal ultrasonography results in a frequent antenatally observation of hydronephrosis, ureteropelvic junction obstruction (UPJO) accounting for the greatest fraction of congenital obstructive nephropathy. UPJO may be considered, in most cases, as a functional obstructive condition, depending on defective fetal smooth muscle/nerve development at this level, with lack of peristaltic wave propagation--aperistaltic segment--and, therefore, poor urine ejection from the renal pelvis into the ureter. The UPJO-related physiopathologic events are, at first, the compliant dilatation of renal pelvis that, acting as hydraulic buffer, protects the renal parenchyma from the rising intrapelvic pressure-related potential damages, and, subsequently, beyond such phase of dynamic balance, the tubular cell stretch-stress induced by increased intratubular pressure and following parenchymal inflammatory lesions: inflammatory infiltrates, fibroblast proliferation, activation of myofibroblasts, tubulo-interstitial fibrosis. Reactive oxygen species (ROS), nitric oxide (NO), several chemo- and cytokines, growth factors, prostaglandins and eicosanoids, angiotensin-II are the main pathogenetic mediators of the obstructive nephropathy. Apoptosis of tubular cells is the major cause of the tubular atrophy, together with epithelial-mesenchymal transdifferentiation. Some criticisms on tout court semantic renal pelvis dilatation-obstruction connection have been raised considering that the renal pelvis expansion isn't, in any case, linked to an ostructive condition, as it may be verified by diuretic (furosemide) renogram together with scintiscan-based evaluation of differential renal function. In this regard, rather than repetitive invasive nuclear procedures that expose the children to ionizing radiations, an intriguing noninvasive strategy, based on the evaluation of urinary biomarkers and urinary proteome, can define the UPJO-related possible progress of parenchymal lesions

  17. Effect of low dose nicotinic acid on hyperphosphatemia in patients with end stage renal disease.

    PubMed

    Zahed, N S; Zamanifar, N; Nikbakht, H

    2016-01-01

    Hyperphosphatemia is a risk factor for ectopic calcification and coronary artery diseases in end stage renal diseases (ESRD). The aim of this study was to assess the effect of low-dose nicotinic acid on hyperphosphatemia in patients with ESRD. This randomized, double-blind clinical trial was done on 70 ESRD patients with serum phosphoure ≥5.5 mg/dl. Patients were randomly divided into two equal groups (n = 35) and the intervention group received niacin 25 mg/day as the initial dose. After 4 weeks, in patients who did not respond to treatment, niacin dose was increased up to 50 mg/dl. At the end of week 8, in case there was no treatment effect, the dose was raised to 100 mg/day. The appropriate response to treatment was defined as serum phosphorous level reductions <5.5 mg/dl. The age was 50.5 ± 14.3 years and duration of dialysis 5.1 ± 5.3 months. In the niacin group, mean phosphorus level decreased from 6.7 ± 0.84 mg/dl at the end of the 1(st) month to 5.8 ± 1.0 mg/dl at the end of the 2(nd) month and to 4.4 ± 1.4 mg/dl at the end of the 3(rd) month (P = 0.004). In the placebo group, mean phosphorus level increased from 6.5 ± 1.2 mg/dl to 7.2 ± 0.91 mg/dl at the end of the 3(rd) month (P = 0.006). In the niacin group, high density lipoprotein (HDL) increased significantly from 45.00 ± 14.9 to 47.2 ± 11.6 (P = 0.009). We conclude that niacin (100 mg/day) decreased phosphorus serum level and increased HDL serum level in patients on dialysis. PMID:27512294

  18. Effect of low dose nicotinic acid on hyperphosphatemia in patients with end stage renal disease

    PubMed Central

    Zahed, N. S.; Zamanifar, N.; Nikbakht, H.

    2016-01-01

    Hyperphosphatemia is a risk factor for ectopic calcification and coronary artery diseases in end stage renal diseases (ESRD). The aim of this study was to assess the effect of low-dose nicotinic acid on hyperphosphatemia in patients with ESRD. This randomized, double-blind clinical trial was done on 70 ESRD patients with serum phosphoure ≥5.5 mg/dl. Patients were randomly divided into two equal groups (n = 35) and the intervention group received niacin 25 mg/day as the initial dose. After 4 weeks, in patients who did not respond to treatment, niacin dose was increased up to 50 mg/dl. At the end of week 8, in case there was no treatment effect, the dose was raised to 100 mg/day. The appropriate response to treatment was defined as serum phosphorous level reductions <5.5 mg/dl. The age was 50.5 ± 14.3 years and duration of dialysis 5.1 ± 5.3 months. In the niacin group, mean phosphorus level decreased from 6.7 ± 0.84 mg/dl at the end of the 1st month to 5.8 ± 1.0 mg/dl at the end of the 2nd month and to 4.4 ± 1.4 mg/dl at the end of the 3rd month (P = 0.004). In the placebo group, mean phosphorus level increased from 6.5 ± 1.2 mg/dl to 7.2 ± 0.91 mg/dl at the end of the 3rd month (P = 0.006). In the niacin group, high density lipoprotein (HDL) increased significantly from 45.00 ± 14.9 to 47.2 ± 11.6 (P = 0.009). We conclude that niacin (100 mg/day) decreased phosphorus serum level and increased HDL serum level in patients on dialysis. PMID:27512294

  19. Effect of Icodextrin Solution on the Preservation of Residual Renal Function in Peritoneal Dialysis Patients

    PubMed Central

    Chang, Tae Ik; Ryu, Dong-Ryeol; Yoo, Tae-Hyun; Kim, Hyung Jong; Kang, Ea Wha; Kim, Hyunwook; Chang, Jae Hyun; Kim, Dong Ki; Moon, Sung Jin; Yoon, Soo Young; Han, Seung Hyeok

    2016-01-01

    Abstract Although icodextrin solution has been highlighted in the fluid management compared to glucose-based solutions, proof of a beneficial effect of icodextrin solution on residual renal function (RRF) is lacking. We conducted a multicenter prospective randomized controlled open-label trial to investigate whether icodextrin solution can preserve RRF. One hundred patients with urine volume ≥750 mL/day from 8 centers in Korea were randomly assigned to receive 1 exchange of icodextrin solution for a ≥8 hour-dwell time and 2 exchanges of 1.5% glucose-based biocompatible neutral pH solution or 1 exchange of ≥2.5% and 2 exchanges of 1.5% glucose-based biocompatible solutions. Using mixed-effects general linear models, we analyzed changes in residual glomerular filtration rate (GFR) and daily urine volume at 1 year. Forty-nine patients were assigned to the icodextrin group and 51 to the glucose solution group. During follow-up, the slope of the decline in residual GFR was −0.170 mL/min/month/1.73 m2 in the icodextrin group, while it was −0.155 mL/min/month/1.73 m2 in the glucose solution group (95% confidence interval [CI], −0.06 to 0.10; P = 0.701). Daily urine volume decreased faster in the glucose solution group than in the icodextrin group (−31.02 vs −11.88 mL per month; 95% CI, −35.85 to −2.44; P = 0.025). Results were consistent when we analyzed using intention-to-treat and per protocol principles. There were no differences in fluid status, peritoneal ultrafiltration, and peritoneal transport between groups during follow-up. This study clearly showed that icodextrin solution preserves residual urine volume better than glucose solution. PMID:27043667

  20. Improvement of renal function after opening occluded atherosclerotic renal arteries.

    PubMed

    Kanamori, Hiroshi; Toma, Masanao; Fukatsu, Atsushi

    2009-09-01

    Percutaneous transluminal renal angioplasty (PTRA) with stenting has been effective in the control of hypertension, renal function and pulmonary edema caused by atherosclerotic renal artery stenosis (ARAS). However, concerning the viability of renal function, this procedure has not been fully established, especially in the presence of renal atrophy or severe renal parenchymal disease. We report a dramatically improved case of acute renal failure caused by acute worsening ARAS treated by stenting. A 72-year-old female was admitted for accelerated renal dysfunction (serum ceatinine; 1.2-2.3 mg/dl) and hypertension (190/100 mmHg). At 10 days after admission, the patient's serum ceatinine increased to 6.7 mg/dl, her pulmonary edema was exaggerated and hemodialysis was required. Ultrasonography showed bilateral high-echoic kidneys, but no apparent finding of renal artery stenosis (RAS). At day 15, computed tomographic angiography indicated bilateral ostial RAS. Renal angiography demonstrated total occlusion of the right and severe (90%) disease in the left. ARAS was diagnosed by intravascular ultrasonography. The guidewire was inserted in both renal arteries, PTRA with stenting was performed in the right and a stent was directly implanted in the left. Immediately, each kidney enlarged to almost normal size, leading to satisfactory urination. She was released from hemodialysis the next day since her serum creatinine was normal and the pulmonary edema was improved. Although there is still no reliable prognostic factor including resistive index or kidney size, it is important that PTRA with stenting in ARAS should be considered in a case of accelerated renal dysfunction because of the possible improvement. PMID:19726830

  1. The Effect of Autophagy on Inflammation Cytokines in Renal Ischemia/Reperfusion Injury.

    PubMed

    Ling, Haibin; Chen, Hongguang; Wei, Miao; Meng, Xiaoyin; Yu, Yonghao; Xie, Keliang

    2016-02-01

    Acute kidney injury (AKI) is characterized by a rapid loss of kidney function and an antigen-independent inflammatory process that causes tissue damage, which was one of the main manifestations of kidney ischemia/reperfusion (I/R). Recent studies have demonstrated autophagy participated in the pathological process of acute kidney injury. In this study, we discuss how autophagy regulated inflammation response in the kidney I/R. AKI was performed by renal I/R. Autophagy activator rapamycin (Rap) and inhibitor 3-methyladenine (MA) were used to investigate the role of autophagy on kidney function and inflammation response. After the experiment, kidney tissues were obtained for the detection of autophagy-related protein microtubule-associated protein light chain 3(LC3)II, Beclin1, and Rab7 and lysosome-associated membrane protein type (LAMP)2 protein by reverse transcription-polymerase chain reaction (PT-PCR) and Western blotting, and histopathology and tissue injury scores also. The blood was harvested to measure kidney function (creatinine (Cr) and blood urea nitrogen (BUN) levels) after I/R. Cytokines TNF-α, IL-6, HMGB1, and IL-10 were measured after I/R. I/R induced the expression of LC3II, Beclin1, LAMP2, and Rab7. The activation and inhibition of autophagy by rapamycin and 3-MA were promoted and attenuated histological and renal function in renal I/R rats, respectively. Cytokines TNF-α, IL-6, and HMGB1 were decreased, and IL-10 was further increased after activation of autophagy treated in I/R rats, while 3-MA exacerbated the pro-inflammatory cytokines TNF-α, IL-6, HMGB1, and anti-inflammatory cytokine IL-10 in renal I/R. I/R can activated the autophagy, and autophagy increase mitigated the renal injury by decreasing kidney injury score, levels of Cr and BUN after renal I/R, and inflammation response via regulating the balance of pro-inflammation and anti-inflammation cytokines. PMID:26412257

  2. Effects of Nigella sativa oil and ascorbic acid against oxytetracycline-induced hepato-renal toxicity in rabbits

    PubMed Central

    Abdel-Daim, Mohamed M.; Ghazy, Emad W.

    2015-01-01

    Objective(s): Oxytetracycline (OTC) is a broad spectrum antibiotic widely used for treatment of a wide range of infections. However, its improper human and animal use leads to toxic effects, including hepatonephrotoxicity. Our objective was to evaluate protective effects of Nigella sativa oil (NSO) and/or ascorbic acid (AA), against OTC-induced hepatonephrotoxicity in rabbits. Materials and Methods: Forty male white New Zealand rabbits were divided into 5 groups of eight each. The 1st group (control) was given saline. The 2nd group was given OTC (200 mg/kg, orally). The 3rd and 4th groups were orally administered NSO and AA (2 ml/kg and 200 mg/kg respectively) 1 hr before OTC administration at the same dose regimen used for the 2nd group. Both NSO and AA were given in combination for the 5th group along with OTC administration. Serum biochemical parameters related to liver and kidney injury were evaluated, and lipid peroxidation as well as antioxidant markers in hepatic and renal tissues were examined. Results: OTC-treated animals revealed significant alterations in serum biochemical hepato-renal injury markers, and showed a markedly increase in hepato-renal lipid peroxidation and inhibition in tissue antioxidant biomarkers. NSO and AA protect against OTC-induced serum and tissue biochemical alterations when each of them is used alone or in combination along with OTC treatment. Furthermore, both NSO and AA produced synergetic hepatoprotective and antioxidant properties. Conclusion: The present study revealed the preventive role of NSO and/or AA against the toxic effects of OTC through their free radical-scavenging and potent antioxidant activities. PMID:25945233

  3. Effect of melatonin supplementation and cross-fostering on renal glutathione system and development of hypertension in spontaneously hypertensive rats.

    PubMed

    Siew-Keah, Lee; Sundaram, Arunkumar; Sirajudeen, K N S; Zakaria, Rahimah; Singh, H J

    2014-03-01

    Antenatal and postnatal environments are hypothesised to influence the development of hypertension. This study investigates the synergistic effect of cross-fostering and melatonin supplementation on the development of hypertension and renal glutathione system in spontaneously hypertensive rats (SHR). In one experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy. Immediately following delivery, 1-day-old male pups were fostered either to SHR (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until weaning on day 21. Upon weaning, melatonin supplementation was continued to these pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured. Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was not significantly different from that in Mel-shr-SHR. Renal glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It appears that combination of cross-fostering and melatonin supplementation exerts no synergistic effect on delaying the rise in blood pressure in SHR. The elevated GPx and GST activities are likely to be due to the effect of melatonin supplementation. PMID:23975651

  4. Harvest-induced evolution and effective population size.

    PubMed

    Kuparinen, Anna; Hutchings, Jeffrey A; Waples, Robin S

    2016-06-01

    Much has been written about fishery-induced evolution (FIE) in exploited species, but relatively little attention has been paid to the consequences for one of the most important parameters in evolutionary biology-effective population size (N e). We use a combination of simulations of Atlantic cod populations experiencing harvest, artificial manipulation of cod life tables, and analytical methods to explore how adding harvest to natural mortality affects N e, census size (N), and the ratio N e/N. We show that harvest-mediated reductions in N e are due entirely to reductions in recruitment, because increasing adult mortality actually increases the N e/N ratio. This means that proportional reductions in abundance caused by harvest represent an upper limit to the proportional reductions in N e, and that in some cases N e can even increase with increased harvest. This result is a quite general consequence of increased adult mortality and does not depend on harvest selectivity or FIE, although both of these influence the results in a quantitative way. In scenarios that allowed evolution, N e recovered quickly after harvest ended and remained higher than in the preharvest population for well over a century, which indicates that evolution can help provide a long-term buffer against loss of genetic variability. PMID:27247617

  5. Cardiovascular and renal effects of weight reduction in obesity and the metabolic syndrome.

    PubMed

    Cohen, Jordana B; Cohen, Debbie L

    2015-05-01

    Obesity is a critical public health issue worldwide. Patients with obesity have markedly increased morbidity and mortality compared to the general population. The increased health risks of obesity in part are due to its close association with each of the other components of the metabolic syndrome, including hypertension, dyslipidemia, and insulin resistance. Accordingly, obese individuals are at particularly increased risk of cardiovascular disease and chronic kidney disease. Modest weight loss results in improvements in serum cholesterol levels, blood pressure, and glycemic profiles. Lifestyle interventions for weight loss have long been the mainstay of treatment in obesity. However, the existing literature demonstrates limited weight loss sustainability and inconsistent cardiovascular and renal benefits using these modalities. In addition to improvements in intermediate risk factors, surgical interventions provide a more lasting impact on long-term cardiovascular and renal outcomes, though carry higher short-term risks due to perioperative complications. PMID:25833456

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

    NASA Astrophysics Data System (ADS)

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

    2007-04-01

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

  7. The evolution of cooperation by the Hankshaw effect.

    PubMed

    Hammarlund, Sarah P; Connelly, Brian D; Dickinson, Katherine J; Kerr, Benjamin

    2016-06-01

    The evolution of cooperation-costly behavior that benefits others-faces one clear obstacle. Namely, cooperators are always at a competitive disadvantage relative to defectors, individuals that reap the benefits, but evade the cost of cooperation. One solution to this problem involves genetic hitchhiking, where the allele encoding cooperation becomes linked to a beneficial mutation, allowing cooperation to rise in abundance. Here, we explore hitchhiking in the context of adaptation to a stressful environment by cooperators and defectors with spatially limited dispersal. Under such conditions, clustered cooperators reach higher local densities, thereby experiencing more mutational opportunities than defectors. Thus, the allele encoding cooperation has a greater probability of hitchhiking with alleles conferring stress adaptation. We label this probabilistic enhancement the "Hankshaw effect" after the character Sissy Hankshaw, whose anomalously large thumbs made her a singularly effective hitchhiker. Using an agent-based model, we reveal a broad set of conditions that allow the evolution of cooperation through this effect. Additionally, we show that spite, a costly behavior that harms others, can evolve by the Hankshaw effect. While in an unchanging environment these costly social behaviors have transient success, in a dynamic environment, cooperation and spite can persist indefinitely. PMID:27110846

  8. Shape Effect in Aggregation and Thermal Evolution of Comet Nuclei

    NASA Astrophysics Data System (ADS)

    Lasue, Jeremie; Coradini, A.; Levasseur-Regourd, A. C.; Botet, R.; De Sanctis, M. C.; Capria, M. T.; Magni, G.; Turrini, D.

    2007-10-01

    Comet nuclei are considered as the most pristine bodies of the Solar System. Their study consequently sheds an important light on the processes occurring during the initial stages of the solar system formation. Simulations have been developed in our teams to describe new aspects of comet formation and evolution. Particle aggregation simulations taking into account age-related cohesive energy of cometesimals during accretions in the Kuiper belt can be used to interpret the layered structure and surface features observed for comet 9P/Tempel 1 [1] and quantify the tensile strengths of these objects. Thermal evolution models of comet nuclei have been rather successful in explaining global aspects of comet observations [2]. A new quasi-3D approach for non-spherically shaped comet nuclei has been developed to analyse the effect of the irregular shapes (non-spherical shapes, mountain-like and crater-like features) of comet nuclei on their thermal evolution, on the local crust formation and the onset of their activity. Our simulations suggest that depressions on the surface play a role in the internal stratification of the nucleus and can disappear in a comet's lifetime [3]. New simulations specifically designed for the orbital history and irregular shape of 67P/Churyumov-Gerasimenko will be presented. These tensile strength indications and activity predictions will provide vital clues for the international Rosetta mission rendezvous that will provide further constraints on the formation and evolution processes of comets. [1] Belton et al., Icarus 187, 332 (2007) [2] DeSanctis et al., Astron. Astrophys. 444, 605 (2005) [3] Lasue et al., in preparation This research has been funded by the French Space Agency (CNES)

  9. Genome-wide profiling to analyze the effects of FXR activation on mouse renal proximal tubular cells

    PubMed Central

    Gui, Ting; Gai, Zhibo

    2015-01-01

    To assess the effect of farnesoid X receptor (FXR), a bile acid nuclear receptor, on renal proximal tubular cells, primary cultured mouse kidney proximal tubular cells were treated with GW4064 (a FXR agonist) or DMSO (as controls) overnight. Analysis of gene expression in the proximal tubular cells by whole genome microarrays indicated that FXR activation induced genes involved in fatty acid degradation and oxidation reduction. Among them, genes involved in glutathione metabolism were mostly induced. Here we describe in details the contents and quality controls for the gene expression and related results associated with the data uploaded to Gene Expression Omnibus (accession number GSE70296). PMID:26697325

  10. Genome-wide profiling to analyze the effects of FXR activation on mouse renal proximal tubular cells.

    PubMed

    Gui, Ting; Gai, Zhibo

    2015-12-01

    To assess the effect of farnesoid X receptor (FXR), a bile acid nuclear receptor, on renal proximal tubular cells, primary cultured mouse kidney proximal tubular cells were treated with GW4064 (a FXR agonist) or DMSO (as controls) overnight. Analysis of gene expression in the proximal tubular cells by whole genome microarrays indicated that FXR activation induced genes involved in fatty acid degradation and oxidation reduction. Among them, genes involved in glutathione metabolism were mostly induced. Here we describe in details the contents and quality controls for the gene expression and related results associated with the data uploaded to Gene Expression Omnibus (accession number GSE70296). PMID:26697325

  11. Environmental evolution: Effects of the origin and evolution of life on Planet Earth

    SciTech Connect

    Margulis, L.; Olendzenski, L.

    1992-01-01

    This book is a multiauthored textbook in planetary evolutionary biogeochemistry, emphasizing the major effects biota have had on the planetary environment and based on a long standing, one semister course at Boston University. A series of chapters described planetary atmospheres in the inner solar system, alternative views on the chemical origin of life, present-day microbial communities and the structures they build, the endosymbiotic origin of eukaryotic cells, and the fossil record of the late Precambrian. Four concluding chapters discuss the Phanerozoic, including the Gaia hypotheseis, plate tectonics, plant secondary compounds, and the role of chromosome fission in mammaliean evolution. A section on assignments, presentations, supplementary material, and background reading, and a comprehensive glossary are included.

  12. Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Cabozantinib.

    PubMed

    Nguyen, Linh; Holland, Jaymes; Ramies, David; Mamelok, Richard; Benrimoh, Natacha; Ciric, Sabrina; Marbury, Thomas; Preston, Richard A; Heuman, Douglas M; Gavis, Edith; Lacy, Steven

    2016-09-01

    Cabozantinib is a tyrosine kinase inhibitor approved for the treatment of patients with progressive, metastatic medullary thyroid cancer. Two clinical pharmacology studies were conducted to characterize single-dose pharmacokinetics (PK) of cabozantinib in renally or hepatically impaired subjects. Study 1 enrolled 10 subjects, each with mild or moderate impairment of renal function; 12 healthy subjects were matched to the moderate group for age, sex, and body mass index (BMI). Study 2 enrolled 8 males each with mild or moderate hepatic impairment; 10 healthy males were matched to the moderate group for age, BMI, and ethnicity. All subjects received one 60 mg cabozantinib oral capsule dose followed by PK sampling over 21 days. Plasma concentration and protein binding were determined by liquid chromatography tandem mass spectrometry and equilibrium dialysis, respectively. PK parameters were computed using noncompartmental methods. Geometric least squared mean (LSM) ratios for plasma cabozantinib AUC0-∞ for impaired to normal organ function cohorts were (1) approximately 30% and 6% higher in subjects with mild and moderate renal impairment, respectively, and (2) approximately 81% and 63% higher in subjects with mild and moderate hepatic impairment, respectively. The percentage of unbound drug was slightly higher in both moderately impaired cohorts. No deaths or discontinuations due to adverse events occurred in either study. Cabozantinib should be used with caution in subjects with mild or moderate renal impairment. Subjects with mild or moderate hepatic impairment administered cabozantinib should be monitored closely for potential treatment-emergent drug toxicity that may necessitate a dose hold or reduction. PMID:26865195

  13. Effect of tabs on the evolution of an axisymmetric jet

    NASA Technical Reports Server (NTRS)

    Zaman, K. B. M. Q.; Samimy, M.; Reeder, M. F.

    1991-01-01

    The effect of vortex generators, in the form of small tabs at the nozzle exit, on the evolution of an axisymmetric jet was investigated experimentally over a jet Mach number range of 0.34 to 1.81. The effects of one, two, and four tabs were studied in comparison with the corresponding case without a tab. Each tab introduced an indentation in the shear layer, apparently through the action of streamwise vortices which appeared to be of the trailing vortex type originating from the tips of the tab rather that of the necklace vortex type originating from the base of the tab. The resultant effect of two tabs, placed at diametrically opposite locations, was to essentially bifurcate the jet. The influence of the tabs was essentially the same at subsonic and supersonic conditions indicating that compressibility has little to do with the effect.

  14. Developmental plasticity and the evolution of parental effects.

    PubMed

    Uller, Tobias

    2008-08-01

    One of the outstanding challenges for evolutionary biologists is to understand how developmental plasticity can influence the evolutionary process. Developmental plasticity frequently involves parental effects, which might enable adaptive and context-dependent transgenerational transmission of phenotypic strategies. However, parent-offspring conflict will frequently result in parental effects that are suboptimal for parents, offspring or both. The fitness consequences of parental effects at evolutionary equilibrium will depend on how conflicts can be resolved by modifications of developmental processes, suggesting that proximate studies of development can inform ultimate questions. Furthermore, recent studies of plants and animals show how studies of parental effects in an ecological context provide important insights into the origin and evolution of adaptation under variable environmental conditions. PMID:18586350

  15. Cardiovascular abnormalities in end stage renal failure: the effect of anaemia or uraemia?

    PubMed Central

    Morris, K P; Skinner, J R; Hunter, S; Coulthard, M G

    1994-01-01

    Children with end stage renal failure and anaemia have an increased cardiac index and often gross ventricular hypertrophy. Correction of anaemia with recombinant human erythropoietin (r-HuEpo) for less than six months results in a reduction in the cardiac index without a significant reduction in left ventricular hypertrophy. Seven children receiving dialysis (group 1) were studied to determine whether a reduction in left ventricular hypertrophy would occur after a 12 month period of r-HuEpo. A decrease in the cardiac index was seen by six months, and a significant reduction in left ventricular mass index and cardiothoracic ratio was seen by 12 months. Successful renal transplantation also results in a reduction in the cardiac index and left ventricular hypertrophy, but the relative contributions of correction of anaemia and correction of biochemical disturbance is unknown because they usually improve simultaneously. To investigate this, six children (group 2) who already had a mean haemoglobin concentration of 107 g/l while receiving dialysis were followed up for 12 months after successful transplantation. They showed no significant change in haemoglobin concentration, but a dramatic improvement in biochemistry. There was no significant change in cardiovascular function. Anaemia is the more dominant influence on cardiovascular function in end stage renal failure. PMID:7944530

  16. Diagnostic effects of edge sharpening filtration and magnification on digitally subtracted renal images.

    PubMed

    Kimme-Smith, C; Gomes, A S; Cochran, S T; Barbaric, Z L; Lois, J F

    1986-01-01

    The improved appearance of digital radiographs filtered to improve local contrast and sharpen edges has not increased acceptance of these images by radiologists. Furthermore, many radiologists assert that correct diagnosis is not improved with these filtered images. This study was designed to test this assertion for digital subtraction angiograms (DSA) of renal images. Four experiments are described. First, phantom studies identified filters and their parameters thought likely to be acceptable and useful in diagnosing renal images formed by DSA. Second, these filters and parameters were then tested on medical images to assess their acceptance by radiologists. Third, display modes of windowing, positive/negative presentation, and magnification were varied for filtered and unfiltered images to assess preferences of radiologists. Fourth, filtered and unfiltered magnified images were used to test improved diagnosis. In the final experiment, 148 images from 33 renal studies (15 normal, 18 abnormal) were magnified, gray level windowed, and filtered. Diagnosis was not improved by the two edge sharpening filters tested. PMID:3540567

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

    SciTech Connect

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

    2008-12-01

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

  18. Effect of Erythropoietin on Lymphocytes Apoptosis in Experimental Chronic Renal Failure.

    PubMed

    Osikov, M V; Telesheva, L F; Ageev, Yu I

    2015-07-01

    Recombinant human erythropoietin was injected intraperitoneally in a total dose of 900 U/kg to rats with experimental chronic renal failure. Suspension of lymphocytes from animals with chronic renal failure was used in vitro, erythropoietin was used in concentrations of 30, 15, 7.5, 3.75, and 1.88 U/liter. Intact cells (Annexin-5-FITC(-)/7-AAD(-)), cells with early signs of apoptosis (Annexin-5-FITC(+)/7-AAD(-)), cells with late signs of apoptosis and partially necrotic cells (Annexin-5-FITC(+)/7-AAD(+)), as well as cells with early signs of necrosis (Annexin-5-FITC(-)/7-AAD(+)) were differentiated by fl ow cytometry. It was found that the number of peripheral blood lymphocytes with early and late signs of apoptosis and necrosis increased in chronic renal failure. Erythropoietin at a total dose of 900 U/kg reduced the number of blood lymphocytes with signs of apoptosis and necrosis and thus elevated the number of intact lymphocytes. Erythropoietin in concentrations ranging from 1.88 to 30.0 U/liter dose dependently lowered the number of lymphocytes with early signs of apoptosis and the number of lymphocytes with the signs of late apoptosis and necrosis in vitro. PMID:26205722

  19. Effect of diet on the incidence of and mortality owing to gastritis and renal disease in captive cheetahs (Acinonyx jubatus) in South Africa.

    PubMed

    Lane, E P; Miller, S; Lobetti, R; Caldwell, P; Bertschinger, H J; Burroughs, R; Kotze, A; van Dyk, A

    2012-01-01

    Seventy-two adult cheetahs were evaluated for the degree of gastritis by endoscopic biopsy and for renal disease by serum creatinine. Cheetahs free of Grade 3 gastritis and renal disease were placed on Trial A; remaining cheetahs were placed on Trial B, which ran concurrently. All cheetahs were monitored for 4 years. Cheetahs exited Trial A and entered Trial B if they developed Grade 3 gastritis or renal disease. Cheetahs exited Trial B if they developed clinical gastritis or renal disease that required a dietary change or aggressive medical therapy or died owing to either disease. Cheetahs on Trial A were fed either a supplemented meat diet (N = 26) or commercial cat food (N = 22). Cheetahs on Trial B were fed either the same meat diet (N = 28) or a commercial dry cat food formulated for renal disease (N = 16). Cheetahs fed meat on Trial A had a daily hazard of developing Grade 3 gastritis 2.21 times higher (95% CI 0.95-5.15) than cheetahs fed commercial cat food. This hazard was not statistically significant (P = 0.07). Mean gastritis scores were not significantly different between the two groups. Cheetahs fed commercial cat food in both Trials had lower serum urea levels and higher creatinine levels than those fed meat. Evidence for the effect of diet in cheetahs with gastritis and/or renal disease (Trial B) was inconclusive. The number of cheetahs dying of gastritis or renal disease at the facility has dropped markedly since the study began. These results indicate that diet may play an important role in the incidence of Grade 3 gastritis and that dietary and/or therapeutic management of gastritis may reduce mortality owing to gastritis and renal disease in captive cheetahs. PMID:22083933

  20. Effects of acute beta-adrenoceptor blockade with metoprolol on the renal response to dopamine in normal humans.

    PubMed Central

    Olsen, N V; Lang-Jensen, T; Hansen, J M; Plum, I; Thomsen, J K; Strandgaard, S; Leyssac, P P

    1994-01-01

    The present study investigated the contribution of adrenergic beta 1-receptor stimulation to the cardiovascular and renal effects of low-dose dopamine in eight normal, water-loaded humans. Metoprolol (100 mg) or placebo was administered orally at 08.00 h in a randomized, double-blind fashion on two different days. Renal clearance studies were performed during a 1 h baseline period, two 1 h periods with dopamine infusion (3 micrograms kg-1 min-1), and a 1 h recovery period. Cardiac output was measured by an ultrasonic Doppler method, and lithium clearance (CLLi) was used to estimate proximal tubular outflow. Baseline values of heart rate, systolic pressure and mean arterial pressure decreased with metoprolol compared with placebo, but cardiac output, effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were not significantly changed. Metoprolol significantly decreased baseline CLLi and sodium clearance (CLNa) by 19% (P < 0.01) and 34% (P < 0.01), respectively. Metoprolol blunted the dopamine-induced increases in heart rate and systolic pressure, but cardiac output increased to the same extent on both study days by 26% (placebo, P < 0.05) and by 31% (metoprolol, P < 0.01), respectively. With and without metoprolol, dopamine did not significantly change GFR, and the percentage increases in ERPF were similar on the two study days (40% (P < 0.001) and 42% (P < 0.001), respectively). Dopamine increased CLLi and CLNa by 31% (P < 0.01) and 114% (P < 0.01), respectively, with placebo, and by 36% (P < 0.01) and 114% (P < 0.01), respectively, with metoprolol. Values during infusion remained significantly lower with metoprolol compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8018456

  1. Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine.

    PubMed

    Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Salsoso, Rocío; Miguel-Carrasco, José L; Fortuño, Ana; Revilla, Elisa; Mate, Alfonso; Vázquez, Carmen M

    2016-10-01

    Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (•) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc. PMID:26918530

  2. Solar wind effects on atmosphere evolution at Venus and Mars

    NASA Technical Reports Server (NTRS)

    Luhmann, Janet G.; Bauer, S. J.

    1992-01-01

    The weak intrinsic magnetism of Venus and Mars leaves these planets subject to some unique atmospheric loss processes. This paper reviews the ways in which material seems to be removed by the solar wind interaction, including atmospheric ion pickup by the solar wind, bulk removal and outflow of ionospheric plasma, and atmospheric sputtering by pickup ions. The factors in the planets' and sun's histories, such as planetary magnetism, solar luminosity, and past solar wind properties, that must ultimately be folded into considerations of the effects of the solar wind interaction on atmosphere evolution are discussed.

  3. Pharmacokinetics in renal disease.

    PubMed

    Levy, G

    1977-04-01

    The physiologic perturbations associated with renal disease can have a pronounced effect on the kinetics of elimination of drugs and their metabolites from the body. Drugs are ordinarily cleared from the body by a number of routes, each of which can be characterized by a clearance value. The sum of these clearances (renal, hepatic, etc.) is the total or body clearance which is inversely proportional to the steady-state plasma concentration produced by a given drug dosage regimen. The quantitative contribution of each route of elimination to the metabolic fate of a drug is proportional to the clearance value of that route relative to the body clearance. As a first approximation, the reduction in the renal clearance of a drug caused by renal disease is proportional to the reduction in the renal clearance of creatinine. The metabolic (biotransformation) clearance of many extensively plasma protein bound drugs is proportional to their free fraction (ratio of concentrations of free to total drug) in plasma. Since severe renal disease causes a reduction in the plasma protein binding of many drugs, the metabolic clearance of such drugs will be increased. The contribution of hemodialysis to the total clearance of a drug depends on the magnitude of the clearance obtained by hemodialysis relative to the magnitude of the body clearance of the drug on a day between dialyses. To compensate for the increased elimination of a drug during hemodialysis, the dosing rate (i.e., the dose per unit of time) must be increased by the factor (hemodialysis clearance and body clearance):body clearance, where body clearance is that during a day between dialyses. Further dosage compensation may be needed if body clearance is increased during hemodialysis due to decreased plasma protein binding of the drug. Under certain conditions, an increased accumulation of pharmacologically active drug metabolites during renal failure becomes a matter of serious concern. PMID:851113

  4. In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells.

    PubMed

    Heussner, A H; Dietrich, D R; O'Brien, E

    2006-04-01

    Hundreds of mycotoxins are known to date and many of them are of great interest with regard to human and animal health since they are detected frequently in plant-derived products. Various mycotoxins may occur simultaneously, depending on the environmental and substrate conditions. Considering this coincident production, it is very likely, that humans and animals are always exposed to mixtures rather than to individual compounds. Therefore, future risk assessments should consider mixture toxicity data. This is particularly true for ochratoxin A (OTA), ochratoxin B (OTB), citrinin (CIT) and occasionally for patulin (PAT) as they are all produced by a number of Penicillium and Aspergillus species. Therefore, these four toxins were chosen to study the interactive effects in vitro, using the well-established porcine renal cell line LLC-PK1 and the MTT reduction test as a cytotoxicity endpoint. By application of a step-wise approach to test combination toxicity, using various full factorial as well as a central composite experimental designs, the interactive (synergistic) cytotoxic effects of the these four toxins were assessed. The results obtained in this study confirm a potential for interactive (synergistic) effects of CIT and OTA and possibly other mycotoxins in cells of renal origin. PMID:16140496

  5. Combined effects of tumor necrosis factor alpha and radiation in the treatment of renal cell carcinoma grown as radia spheroids.

    PubMed

    Van Moorselaar, R J; Schwachöfer, J H; Crooijmans, R P; Van Stratum, P; Debruyne, F M; Schalken, J A

    1990-01-01

    We have investigated the antiproliferative effects of Tumor Necrosis Factor Alpha (TNF) and radiation on a recently described rat renal cell tumor line grown as multicellular tumor spheroids (MTS). Treatment commenced when the spheroids had reached a diameter of 250 microns. TNF was diluted in the tissue culture medium in different concentrations, ranging from 250-1000 ng/ml. TNF monotherapy had a dose-dependent inhibiting effect on spheroid growth. Single-dose irradiation with 2, 4 or 6 Gy also retarded spheroids significantly in their growth. In the combination treatment the highest dose of TNF (1000 ng/ml) was added 4 hours prior to radiation. TNF could not induce a potentiation of the radiation injury at 2 Gy. The combination with 4 Gy, however, had additive and the combination with 6 Gy synergistic antiproliferative effects; in these treatment regimens respectively 2 and 5 out of 24 spheroids were controlled, i.e. cured. These experiments suggest that TNF in combination with radiotherapy may be beneficial for the treatment of renal cell carcinoma or cancer in general. PMID:2285257

  6. Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

    PubMed Central

    Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

    2012-01-01

    Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

  7. Renal failure after ruptured aneurysm.

    PubMed

    Abbott, W M; Abel, R M; Beck, C H; Fischer, J E

    1975-09-01

    The effectiveness of an intravenous nutritional program plus aggressive dialysis was studied in 32 patients with renal failure following ruptured abdominal aortic aneurysm. Each patient was managed postoperatively with a renal failure fluid regimen, consisting of the eight essential amino acids plus dextrose in conjunction with peritoneal dialysis and hemodialysis. This regimen induced salutary metabolic effects temporarily improving the patient's condition in most instances. No technical or septic complications associated with the intravenous dietary therapy occurred. However, the incidence of recovery of renal function was low, and the overall patient survival was only 12.5%. The experience indicates that although this program has been shown to be efficacious in some patients with acute renal failure, it seems of little benefit in those whose renal failure follows ruptured aortic aneurysm. PMID:808197

  8. Protective effect of epimedium combined with oligomeric proanthocyanidins on exercise-induced renal ischemia-reperfusion injury of rats

    PubMed Central

    Zhang, Hua; Sun, Xiao-Qin; Cao, Jian-Min; Zhou, Hai-Tao; Guo, Xian; Wang, Yi

    2014-01-01

    Objective: This paper studied the protective effect and mechanism of epimedium combined with oligomeric proanthocyanidins on exercise-induced renal ischemia-reperfusion injury of rats. Methods: In the experiment, the rats were given exhaustive swimming training and then their blood urea nitrogen (BUN) and other biochemical indexes were measured after they were given gastric perfusion with 6.01 g/kg doze of epimedium and 50 mg/kg doze of oligomeric proanthocyanidins for 56 days. Results: The result indicated that 8 weeks of over training led to ischemia-reperfusion injury of rats. Moreover, their kidney tissues were significantly changed pathologically and renal functions drastically damaged. BUN and serum creatinine increased and EOM group (P < 0.05), OPCOM group (P < 0.05) and EOPCOM group (P < 0.01) were lower than OM group. EOPCOM group was lower than OPCOM group. SOD activity decreased, EOM group (P < 0.05), OPCOM group (P < 0.05), EOPCOM group (P < 0.01) higher than OM group, and EOPCOM group (P < 0.05) higher than OPCOM group. The content of MDA increased, EOM group (P < 0.05), OPCOM group (P < 0.05), EOPCOM group (P < 0.01) lower than OM group, and EOPCOM group (P < 0.05) lower than OPCOM group. Conclusion: Both epimedium and oligomeric proanthocyanidins can boost SOD activity, clean oxygen radicals, clean and alleviate peroxidation of lipids, which exert protection on exercise-induced renal ischemia-reperfusion. The two combined yield a much better result. PMID:25664099

  9. [Renal disease].

    PubMed

    Espinosa-Cuevas, María de Los Ángeles

    2016-09-01

    Chronic renal failure in its various stages, requires certain nutritional restrictions associated with the accumulation of minerals and waste products that cannot be easily eliminated by the kidneys. Some of these restrictions modify the intake of proteins, sodium, and phosphorus. Milk and dairy products are sources of these nutrients. This article aims to inform the reader about the benefits including milk and dairy products relying on a scientific and critical view according to the clinical conditions and the stage of renal disease in which the patient is. PMID:27603894

  10. Renal organogenesis

    PubMed Central

    2011-01-01

    The increasing prevalence of chronic kidney disease in the absence of new treatment modalities has become a strong driver for innovation in nephrology. An increasing understanding of stem cell biology has kindled the prospects of regenerative options for kidney disease. However, the kidney itself is not a regenerative organ, as all the nephrons are formed during embryonic development. Here, we will investigate advances in the molecular genetics of renal organogenesis, including what this can tell us about lineage relationships, and discuss how this may serve to inform us about both the normal processes of renal repair and options for regenerative therapies. PMID:22198432

  11. [Renal colic].

    PubMed

    Pinheiro, J M

    1999-01-01

    The appropriate approach to renal colic, which should be known by the family doctor, is presented. The incidence of this condition in the emergency department of a large general hospital is described as well as the physiopathology of pain, its clinical aspects and the therapeutic attitudes. Renal colic is frequent, it is often possible to diagnose the clinical aspects and general practitioners have the competence for treatment. The use of analgesic drugs, in the correct dosage, is enough to relieve pain and suffering in most of the patients. PMID:10423866

  12. Evolution of the violin: The law of effect in action.

    PubMed

    Wasserman, Edward A; Cullen, Patrick

    2016-01-01

    As is true for most other human inventions, the origin of the violin is unknown. What is known is that this popular and versatile instrument has notably changed over the course of several hundred years. At issue is whether those evolutionary changes in the construction of the violin are the result of premeditated, intelligent design or whether they arose through a trial-and-error process. Recent scientific evidence favors the latter account. Our perspective piece puts these recent empirical findings into a comprehensive selectionist framework. According to this view, the many things we do and make--like violins--arise from a process of variation and selection which accords with the law of effect. Contrary to popular opinion, there is neither mystique nor romance in this process; it is as fundamental and ubiquitous as the law of natural selection. As with the law of natural selection in the evolution of organisms, there is staunch resistance to the role of the law of effect in the evolution of human inventions. We conclude our piece by considering several objections to our perspective. PMID:26569015

  13. Advanced glycosylation endproducts block the antiproliferative effect of nitric oxide. Role in the vascular and renal complications of diabetes mellitus.

    PubMed

    Hogan, M; Cerami, A; Bucala, R

    1992-09-01

    Advanced glycosylation endproducts (AGEs) accumulate on long-lived tissue proteins such as basement membrane collagen and have been implicated in many of the long-term complications of diabetes mellitus. These products originate from glucose-derived Schiff base and Amadori products but undergo a series of complex rearrangement reactions to form ultimately protein-bound, fluorescent heterocycles. AGEs can react with and chemically inactivate nitric oxide (NO), a potent endothelial cell-derived vasodilator and antiproliferative factor. Since mesenchymal cell proliferation is an early and characteristic lesion of diabetic vasculopathy and glomerulopathy, we investigated the possibility that collagen-bound AGEs functionally inactivate the antiproliferative effect of NO. In model cell culture systems, AGEs were found to block the cytostatic effect of NO on aortic smooth muscle and renal mesangial cells. The inactivation of endothelial cell-derived NO by basement membrane AGEs may represent a common pathway in the development of the accelerated vascular and renal disease that accompany long-term diabetes mellitus. PMID:1522220

  14. Effects of telmisartan and olmesartan on insulin sensitivity and renal function in spontaneously hypertensive rats fed a high fat diet.

    PubMed

    Yanagihara, Hayato; Ushijima, Kentaro; Arakawa, Yusuke; Aizawa, Ken-Ichi; Fujimura, Akio

    2016-07-01

    Although telmisartan, an angiotensin II receptor blocker (ARB), has an agonistic action for proliferator-activated receptor (PPAR)-γ in vitro, it remains to be determined whether telmisartan exerts such an action in vivo using a non-toxic dose (<5 mg/kg in rats). To address the issue, telmisartan (2 mg/kg) and olmesartan (2 mg/kg), another ARB without PPAR-γ agonistic action, were given to spontaneously hypertensive rats (SHR) fed a high fat diet (HFD). HFD decreased plasma adiponectin, and caused insulin resistance, hypertriglyceridemia and renal damage, which were improved by ARBs. Protective effects of telmisartan and olmesartan did not significantly differ. In addition, in vitro study showed that 1 μM of telmisartan did not elevate the mRNA expression of adipose protein 2, which is a PPAR-γ-stimulated adipogenic marker gene, in preadipocytes with 3% albumin. To obtain 1 μM of plasma concentration, oral dose of telmisartan was calculated to be 6 mg/kg, which indicates that PPAR-γ agonistic action is negligible with a non-toxic dose of telmisartan (<5 mg/kg) in rats. This study showed that 2 mg/kg of telmisartan and olmesartan ameliorated insulin resistance, hypertriglyceridemia and renal damage in SHR fed a HFD. As beneficial effects of telmisartan and olmesartan did not significantly differ, these were mediated through the PPAR-γ-independent actions. PMID:27430988

  15. Effect of Huai Qi Huang on Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells through miR-200a

    PubMed Central

    Pu, Jinyun; Zhang, Yu; Zhou, Jianhua

    2016-01-01

    Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is a vital mechanism of renal fibrosis. Mounting evidence suggests that miR-200a expression decreases in tubular epithelial cells in unilateral ureteral obstruction (UUO) rats. Moreover, it has been demonstrated that Huai Qi Huang (HQH) can ameliorate tubulointerstitial damage in adriamycin nephrosis and delay kidney dysfunction in primary glomerular disease. However, the effect of HQH on EMT of tubular epithelial cells in UUO rats and its molecular mechanism is unclear. In order to explore the effect of HQH on EMT and its molecular mechanism in renal fibrosis, in vitro and in vivo experiments were performed in our study. Our results showed that HQH increased miR-200a expression in UUO rats and in TGF-β1 stimulated NRK-52E cells. Meanwhile, HQH decreased ZEB1 and ZEB2 (the transcriptional repressors of E-cadherin), α-SMA expression in renal tubular epithelial cells in vitro and in vivo. Furthermore, we found that HQH protected kidney from fibrosis in UUO rats. The results demonstrated that HQH regulated miR-200a/ZEBs pathway and inhibited EMT process, which may be a mechanism of protecting effect on tubular cells in renal fibrosis. PMID:26884796

  16. Effects of recombinant human brain natriuretic peptide on renal function in patients with acute heart failure following myocardial infarction

    PubMed Central

    Wang, Yanbo; Gu, Xinshun; Fan, Weize; Fan, Yanming; Li, Wei; Fu, Xianghua

    2016-01-01

    Objective: To investigate the effect of recombinant human brain natriuretic peptide (rhBNP) on renal function in patients with acute heart failure (AHF) following acute myocardial infarction (AMI). Methods: Consecutive patients with AHF following AMI were enrolled in this clinical trial. Eligible patients were randomly assigned to receive rhBNP (rhBNP group) or nitroglycerin (NIT group). Patients in the rhBNP group received rhBNP 0.15 μg /kg bolus injection after randomization followed by an adjusted-dose (0.0075-0.020 μg/kg/min) for 72 hours, while patients in NIT received infusion of nitroglycerin with an adjusted-dose (10-100 μg/kg/min) for 72 hours in NIT group. Standard clinical and laboratory data were collected. The levels of serum creatinine (SCr), urea, β-2 microglobulin and cystatin C were measured at baseline and repeated at the end of the 24, 48 and 72 hours after infusion. The primary end point was the incidence of acute renal dysfunction, which was defined as an increase in SCr > 0.5 mg/dl (> 44.2 μmol/L) or 25% above baseline SCr value. The occurrence of major adverse cardiac event (MACE) was followed up for 1 month. Results: Of the 50 patients enrolled, 26 were randomly assigned to rhBNP and 24 to nitroglycerin (NIT). There were no significant differences in baseline characteristics between the two groups (all P > 0.05). The baseline concentrations of SCr, urea, β-2 microglobulin and cystatin C at admission were similar in the two groups. However, the concentrations of SCr and urea were significantly higher in rhBNP group than those in NIT group at hour 24 and 48 after treatments (all P < 0.01). For both groups, the concentrations of SCr, urea, β-2 microglobulin and cystatin C were not significant changed compared with baseline levels. The levels of systolic blood pressure (SBP) and diastolic blood pressures (DBP) at admission were also similar between the two groups. In rhBNP group, levels of SBP and DBP decreased significantly at hour 24

  17. Glucuretic effects and renal safety of dapagliflozin in patients with type 2 diabetes

    PubMed Central

    2015-01-01

    Dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor approved as a treatment for type 2 diabetes mellitus (T2DM) in the United States, the European Union and other countries. Dapagliflozin increases renal glucose excretion in an insulin-independent manner, and its mechanism of action is complementary to those of other antidiabetes medications. When used as monotherapy or in combination with other oral antidiabetes medications or insulin, dapagliflozin improves glycemic measures in patients with T2DM. Dapagliflozin treatment is also associated with weight reduction and a decrease in blood pressure, both of which may be beneficial in patients with T2DM. Because of its mechanism of action, dapagliflozin has a low intrinsic propensity to cause hypoglycemia. Overall, dapagliflozin is well tolerated, with the frequency of most adverse events similar to that seen with placebo. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in dapagliflozin-treated groups compared with placebo groups. In the clinical development program, more cases of newly diagnosed bladder cancer were reported for patients treated with dapagliflozin (0.17%) compared with placebo or comparator (0.03%). Although there were not enough cases to determine causality, dapagliflozin should not be used in patients with bladder cancer and should be used with caution in patients with a history of bladder cancer. Dapagliflozin may decrease glomerular filtration rate (GFR), especially in elderly patients and patients with impaired renal function. Renal function should be monitored before initiation of dapagliflozin. Dapagliflozin should not be used in patients with an estimated GFR <60 ml/min/1.73 m2. No cardiovascular safety signals have been detected for dapagliflozin, and a long-term cardiovascular outcomes study is ongoing. Evidence from clinical trials suggests that dapagliflozin is a promising new treatment option for T2DM. PMID

  18. Effect of gene polymorphisms on the levels of calcineurin inhibitors in Indian renal transplant recipients.

    PubMed

    Ashavaid, T; Raje, H; Shalia, K; Shah, B

    2010-07-01

    The outcome of renal transplantation is improved by cyclosporine and tacrolimus. However, its success is limited by drug-induced nephrotoxicity. Therefore, monitoring their levels is important. These levels are influenced mainly by CYP3A4, CYP3A5 and MDR- 1 genes. These levels also affect target molecules of CNIs, mainly IL-2. Inter-individual differences in these levels have been attributed to SNPs in these genes and hence study of these SNPs assumes significance. So far no study has been carried out on Indian renal transplant recipients covering the SNPs of the genes involved in metabolism, efflux and drug target of CNIs, hence the data is lacking for Indian population. The aim is to study A-392G SNP of CYP3A4, A6986G SNP of CYP3A5, C3435T SNP of MDR-1 and T-330G SNP of IL-2 genes and correlate with CNI blood levels. Hundred healthy subjects and 100 consecutive renal transplant recipients; 56 on CsA and 44 on tacrolimus were genotyped by PCR followed by restriction enzyme assay for mentioned SNPs. No significant difference was observed between level/dose (L/D) ratio of CNIs and CYP3A4 and IL-2 SNPs. However, median L/D ratio for tacrolimus was significantly higher in subjects with CYP3A5*3/*3 (n = 24) (P = 0.011) and MDR- 1 3435TT (n = 18) (P = 0.0122). The findings from this study show that homozygous mutant patients for CYP3A5 and MDR-1 gene SNPs could be managed with lower tacrolimus dose to avoid nephrotoxicity. PMID:21072155

  19. Effect of gene polymorphisms on the levels of calcineurin inhibitors in Indian renal transplant recipients

    PubMed Central

    Ashavaid, T.; Raje, H.; Shalia, K.; Shah, B.

    2010-01-01

    The outcome of renal transplantation is improved by cyclosporine and tacrolimus. However, its success is limited by drug-induced nephrotoxicity. Therefore, monitoring their levels is important. These levels are influenced mainly by CYP3A4, CYP3A5 and MDR- 1 genes. These levels also affect target molecules of CNIs, mainly IL-2. Inter-individual differences in these levels have been attributed to SNPs in these genes and hence study of these SNPs assumes significance. So far no study has been carried out on Indian renal transplant recipients covering the SNPs of the genes involved in metabolism, efflux and drug target of CNIs, hence the data is lacking for Indian population. The aim is to study A-392G SNP of CYP3A4, A6986G SNP of CYP3A5, C3435T SNP of MDR-1 and T-330G SNP of IL-2 genes and correlate with CNI blood levels. Hundred healthy subjects and 100 consecutive renal transplant recipients; 56 on CsA and 44 on tacrolimus were genotyped by PCR followed by restriction enzyme assay for mentioned SNPs. No significant difference was observed between level/dose (L/D) ratio of CNIs and CYP3A4 and IL-2 SNPs. However, median L/D ratio for tacrolimus was significantly higher in subjects with CYP3A5*3/*3 (n = 24) (P = 0.011) and MDR- 1 3435TT (n = 18) (P = 0.0122). The findings from this study show that homozygous mutant patients for CYP3A5 and MDR-1 gene SNPs could be managed with lower tacrolimus dose to avoid nephrotoxicity. PMID:21072155

  20. Renal effects of fresh water-induced hypo-osmolality in a marine adapted seal

    NASA Technical Reports Server (NTRS)

    Ortiz, R. M.; Wade, C. E.; Costa, D. P.; Ortiz, C. L.

    2002-01-01

    With few exceptions, marine mammals are not exposed to fresh water; however quantifying the endocrine and renal responses of a marine-adapted mammal to the infusion of fresh water could provide insight on the evolutionary adaptation of kidney function and on the renal capabilities of these mammals. Therefore, renal function and hormonal changes associated with fresh water-induced diuresis were examined in four, fasting northern elephant seal ( Mirounga angustirostris) (NES) pups. A series of plasma samples and 24-h urine voids were collected prior to (control) and after the infusion of water. Water infusion resulted in an osmotic diuresis associated with an increase in glomerular filtration rate (GFR), but not an increase in free water clearance. The increase in excreted urea accounted for 96% of the increase in osmotic excretion. Following infusion of fresh water, plasma osmolality and renin activity decreased, while plasma aldosterone increased. Although primary regulators of aldosterone release (Na(+), K(+) and angiotensin II) were not significantly altered in the appropriate directions to individually stimulate aldosterone secretion, increased aldosterone may have resulted from multiple, non-significant changes acting in concert. Aldosterone release may also be hypersensitive to slight reductions in plasma Na(+), which may be an adaptive mechanism in a species not known to drink seawater. Excreted aldosterone and urea were correlated suggesting aldosterone may regulate urea excretion during hypo-osmotic conditions in NES pups. Urea excretion appears to be a significant mechanism by which NES pups sustain electrolyte resorption during conditions that can negatively affect ionic homeostasis such as prolonged fasting.

  1. Tofacitinab in Renal Transplantation

    PubMed Central

    Zand, Martin S.

    2013-01-01

    Tofacitinib (tositinib, CP-690,550) is a small molecule inhibitor of Janus associated kinases, primarily JAK3 and JAK2, which inhibits cytokine signaling through the IL-2Rγ chain. In this article, we review the mechanism of action of tofacitinib, and pre-clinical and clinical data regarding its use in solid organ transplantation thus far. It is hoped that tofacitinib may form the basis for calcineurin-free immunosuppression, improving renal function while eliminating calcineurin inhibitor renal toxicity. Current studies suggest that tofacitinib is an effective immunosuppressive agent for renal transplantation, but it's use in current protocols carries an increased risk of CMV, BK, and EBV viral infection, anemia and leukopenia, and post-transplant lymphoproliferative disorder. PMID:23849222

  2. Renal adaptation during hibernation

    PubMed Central

    Martin, Sandra L.; Jain, Swati; Keys, Daniel; Edelstein, Charles L.

    2013-01-01

    Hibernators periodically undergo profound physiological changes including dramatic reductions in metabolic, heart, and respiratory rates and core body temperature. This review discusses the effect of hypoperfusion and hypothermia observed during hibernation on glomerular filtration and renal plasma flow, as well as specific adaptations in renal architecture, vasculature, the renin-angiotensin system, and upregulation of possible protective mechanisms during the extreme conditions endured by hibernating mammals. Understanding the mechanisms of protection against organ injury during hibernation may provide insights into potential therapies for organ injury during cold storage and reimplantation during transplantation. PMID:24049148

  3. The effect of hypoxia-induced intrauterine growth restriction on renal artery function.

    PubMed

    Verschuren, M T C; Morton, J S; Abdalvand, A; Mansour, Y; Rueda-Clausen, C F; Compston, C A; Luyckx, V; Davidge, S T

    2012-10-01

    The risk of developing cardiovascular diseases is known to begin before birth and the impact of the intrauterine environment on subsequent adult health is currently being investigated from many quarters. Following our studies demonstrating the impact of hypoxia in utero and consequent intrauterine growth restriction (IUGR) on the rat cardiovascular system, we hypothesized that changes extend throughout the vasculature and alter function of the renal artery. In addition, we hypothesized that hypoxia induces renal senescence as a potential mediator of altered vascular function. We demonstrated that IUGR females had decreased responses to the adrenergic agonist phenylephrine (PE; pEC50 6.50 ± 0.05 control v. 6.17 ± 0.09 IUGR, P < 0.05) and the endothelium-dependent vasodilator methylcholine (MCh; E max 89.8 ± 7.0% control v. 41.0 ± 6.5% IUGR, P < 0.001). In IUGR females, this was characterised by increased basal nitric oxide (NO) modulation of vasoconstriction (PE pEC50 6.17 ± 0.09 IUGR v. 6.42 ± 0.08 in the presence of the NO synthase inhibitor N-nitro-l-arginine methyl ester hydrochloride (l-NAME; P < 0.01) but decreased activated NO modulation (no change in MCh responses in the presence of l-NAME), respectively. In contrast, IUGR males had no changes in PE or MCh responses but demonstrated increased basal NO (PE pEC50 6.29 ± 0.06 IUGR v. 6.42 ± 0.12 plus l-NAME, P < 0.01) and activated NO (E max 37.8 ± 9.4% control v. -0.8 ± 13.0% plus l-NAME, P < 0.05) modulation. No significant changes were found in gross kidney morphology, proteinuria or markers of cellular senescence in either sex. In summary, renal vascular function was altered by hypoxia in utero in a sex-dependent manner but was unlikely to be mediated by premature renal senescence. PMID:25102262

  4. The effect of chronic renal failure on the benzoylecgonine blood level: a case report.

    PubMed

    Guillaud, Daniel A; Jones, Prentiss; Prahlow, Joseph A

    2015-06-01

    Chronic renal failure results in reduced elimination of a variety of substances within the blood, including numerous drugs and their metabolites. This report describes a case of a man who died in jail, after less than 48 hours of being incarcerated, wherein postmortem toxicology testing revealed a blood benzoylecgonine level of 0.25 mg/L with no cocaine detected, suggesting possible recent cocaine use in jail. Autopsy and investigation revealed severe underlying cardiovascular disease and dialysis-dependent CRF, thus accounting for the elevated benzoylecgonine levels and allaying concerns that the man obtained and used cocaine in jail. PMID:25881815

  5. Dynamical Evolution of Asteroids and Meteoroids Using the Yarkovsky Effect

    NASA Technical Reports Server (NTRS)

    Bottke, William F., Jr.; Vokrouhlicky, David; Rubincam, David P.; Broz, Miroslav; Smith, David E. (Technical Monitor)

    2001-01-01

    The Yarkovsky effect is a thermal radiation force which causes objects to undergo semimajor axis drift and spin up/down as a function of their spin, orbit, and material properties. This mechanism can be used to (i) deliver asteroids (and meteoroids) with diameter D < 20 km from their parent bodies in the main belt to chaotic resonance zones capable of transporting this material to Earth-crossing orbits, (ii) disperse asteroid families, with drifting bodies jumping or becoming trapped in mean-motion and secular resonances within the main belt, and (iii) modify the rotation rates of asteroids a few km in diameter or smaller enough to explain the excessive number of very fast and very slow rotators among the small asteroids. Accordingly, we suggest that nongravitational forces, which produce small but meaningful effects on asteroid orbits and rotation rates over long timescales, should now be considered as important as collisions and gravitational perturbations to our overall understanding of asteroid evolution.

  6. Type of hemodialysis and preference for behavioral involvement: interactive effects on adherence in end-stage renal disease.

    PubMed

    Christensen, A J; Smith, T W; Turner, C W; Holman, J M; Gregory, M C

    1990-01-01

    Examined the effects of hemodialysis type (i.e., staff controlled, in center vs. patient controlled, home) and patient preference for behavioral involvement on adherence and emotional adjustment in a sample of 53 patients with end-stage renal disease. Consistent with person x treatment interaction models, higher levels of preference for behavioral involvement were associated with better dietary adherence (i.e., lower serum potassium) for patients receiving dialysis at home but worse dietary adherence for patients receiving treatment in a dialysis center. A similar though weaker patient x treatment type matching pattern was observed for fluid-intake adherence (i.e., interdialytic weight gain). No effects were observed for patients' self-reported depression levels. Possible mechanisms for the interactional effect on adherence are discussed. PMID:2331980

  7. OKT3 escalating dose regimens provide effective therapy for renal allograft rejection.

    PubMed

    Woodle, E S; Bruce, D S; Josephson, M; Cronin, D; Newell, K A; Millis, J M; Piper, J B; O'Laughlin, R; Thistlethwaite, J R

    1996-08-01

    Dose-response relationships for anti-CD3 monoclonal antibody (mAb) therapy remain undefined, particularly with respect to higher dose ranges. The clinical efficacy and safety of an OKT3 dosing regimen that incorporates higher doses (escalating dose regimens) was examined in a pilot trial. Patients undergoing acute rejection were treated with a 7-d course of OKT3 in which the daily OKT3 dose was escalated during treatment course (daily doses 5, 5, 5, 5, 10, 15, 25 mg). The total amount of OKT3 given was equal to a standard 14-d course (70 mg). A total of 10 primary cadaveric renal transplant recipients were treated, and data analyzed from a median follow up of 5 months (range 3-13 months). Pre-OKT3 immunosuppressive therapy consisted of ATGAM induction therapy (n = 8), and corticosteroid rejection therapy (n = 6, 18.6 +/- 11.4 mg/kg). Median time of first rejection was 32 d (12-48 d) and median time to OKT3 was 33 d (range 15-42 d). Pre-OKT3 histology (by Banff criteria) included: mild ACR (n = 6), moderate ACR (n = 2), AVR (n = 1), ACR and acute transplant glomerulopathy (n = 1). Rejection reversal rate with escalating dose OKT3 was 100%, and each patient experienced a rapid reversal of rejection (i.e. reversal within 14 d initiation of OKT3 therapy). Six recurrent rejection episodes were diagnosed in 5 patients with a median time to recurrent rejection of 30 d following cessation of OKT3 therapy. All recurrent rejection episodes were successfully treated (FK 506 n = 4, corticosteroids n = 1, and OKT3 n = 1). CMV disease was limited to a single episode of CMV viremia in one patient. PTLD was observed in one patient who had coexisting vascular rejection at the time of PTLD diagnosis. Short- and long-term graft function is excellent (pre-rejection baseline creatinine 1.8 +/- 0.4 mg/dl, current creatinine 1.75 +/- 0.4 mg/dl). Monitoring of OKT3 serum levels revealed that patients maintained therapeutic serum levels for an average of 4 d following the last OKT3 dose

  8. HOXA13 exerts a beneficial effect in albumin-induced epithelial-mesenchymal transition via the glucocorticoid receptor signaling pathway in human renal tubular epithelial cells.

    PubMed

    Peng, Li; He, Qingnan; Li, Xiaoyan; Shuai, Lanjun; Chen, Haixia; Li, Yongzhen; Yi, Zhuwen

    2016-07-01

    Previous studies have suggested that albumin-induced renal tubular epithelial cell injury contributes to renal interstitial fibrosis. Epithelial-mesenchymal transition (EMT) is known to be a key mechanism in the pathogenesis and progression of renal interstitial fibrosis. Homeobox protein HOX‑A13 (HOXA13) is a nuclear transcriptional factor that has been reported to be involved in renal fibrosis. However, the mechanism underlying the effect of HOXA13 in human serum albumin (HSA)‑induced EMT in HKC renal tubular epithelial cells remains to be elucidated. Thus, the aim of the present study was to investigate the role of HOXA13 in HSA‑induced EMT in HKC cells and the potential mechanism of the glucocorticoid receptor (GR) signaling pathway. The protein and mRNA expression levels of HOXA13, cytokeratin, and vimentin were determined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction in HKC cells, which were co‑incubated with HSA at different concentrations or for different time periods. The results demonstrated that HOXA13 mRNA and protein expression decreased in a dose‑ and time‑dependent manner when induced by HSA in HCK cells. The liposomal transfection experiment suggested that overexpression of HOXA13 activated the GR signal, which inhibits HSA-induced EMT. HOXA13 is involved in HSA‑induced EMT in HKC cells and upregulation of HOXA13 exerts a beneficial effect in EMT, which may be associated with the GR signaling pathway. PMID:27176855

  9. Direct effect of vanadium on citrate uptake by rat renal brush border membrane vesicles (BBMV).

    PubMed

    Sato, Kazuhiro; Kusaka, Yukinori; Akino, Hironobu; Kanamaru, Hiroshi; Okada, Kenichiro

    2002-07-01

    Vanadium pentoxide is used as a catalyst and a ferrovanadium alloy ingredient in automotive steels and in jet engines and airframes. In addition, vanadium is found in fuel oils. Thus, occupational exposures to vanadium pentoxide and trioxide may occur during the cleaning of oil-fired ship boilers, and from oil-fired power station boilers. Occupational exposure to vanadium pentoxide induces green tongue, asthmatic symptoms and albuminuria with cast. Urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In this study, we exposed rat renal brush border membrane vesicles (BBMV) to vanadium pentoxide and examined their citrate uptake characteristics. The preincubation of BBMV with 1 mM V2O5 for 8 hours significantly inhibited citrate uptake compared with that of BBMV without V2O5, preincubation. These findings indicate that the preincubation of BBMV with vanadium pentoxide results in a time-dependent inhibition of citrate uptake by BBMV. These findings might contribute to nephrotoxicity in vanadium exposure. PMID:12141377

  10. Temporary abdominal closure: a prospective evaluation of its effects on renal and respiratory physiology.

    PubMed

    Sugrue, M; Jones, F; Janjua, K J; Deane, S A; Bristow, P; Hillman, K

    1998-11-01

    This study prospectively analyzed outcomes in 49 consecutive patients undergoing temporary abdominal closure (TAC) between 1993 and 1996 at a single university hospital. There were 37 males and 12 females, mean age was 57 years (range, 25-79 years), mean Acute Physiology and Chronic Health Evaluation score was 27 (+7.8 SD), and mean Simplified Acute Physiology II score was 53.0 (+/-15.4). The reason for TAC was decompression in 22 patients, inability to close the abdomen in 10 patients, to facilitate reexploration for sepsis in 8 patients, and multifactorial in 9 patients. After TAC, there was a significant reduction in intra-abdominal pressure from 24.2+/-9.3 to 14.1+/-5.5 mm Hg and improvement in lung dynamic compliance from 24.1+/-7.9 to 27.6+/-9.4 mL/cm H2O (p < 0.05). Although 10 patients experienced brisk diuresis, there was no significant improvement in renal function; in fact, serum creatinine increased. The median length of stay was 35 days (range, 1-232 days). The mean number of abdominal operations after mesh insertion was 2.6+/-2.4. There were 21 deaths, for a standardized mortality rate of 0.80. Although it achieved significant reductions in abdominal pressures and improved lung dynamic compliance, TAC did not result in improved renal function or patient oxygenation. PMID:9820703

  11. Continuous intragastric delivery of fenoldopam: relationship between plasma concentration and effects on renal function.

    PubMed Central

    Ziemniak, J A; Boppana, V K; Cyronak, M J; Beck, T R; Familiar, R G; Dubb, J W; Allison, N L; Stote, R M

    1988-01-01

    1. The pharmacodynamics of the dopamine DA1 agonist fenoldopam were examined in six healthy male volunteers after constant intragastric infusions of fenoldopam at dosages of 0, 10, 25, 50 and 75 mg h-1 for 6 h. 2. Hourly p-aminohippurate (PAH) clearance was used to assess fenoldopam induced renal plasma flow changes. Marked dose-related increases in renal plasma flow were noted with a maximal increase of 65% over baseline values of 711 ml min-1 being seen at the 75 mg h-1 rate. No changes in sodium excretion and glomerular filtration rate were observed. 3. Mean steady-state fenoldopam plasma concentrations were related to mean PAH clearance based on an Emax model (r = 0.996) with an Emax of 1350 ml min-1 and an EC50 of 6.2 ng ml-1. 4. Mean steady-state plasma concentrations of fenoldopam-7-sulphate and fenoldopam-8-sulphate failed to increase with dose but were linearly correlated to mean PAH changes (r = 0.998, r = 0.981 respectively). 5. These results support the concept of extending fenoldopam's duration of action through the development of an oral sustained delivery system. PMID:2896014

  12. Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma

    PubMed Central

    Nakamura, Ritsuko; Oyama, Takeru; Tajiri, Ryosuke; Mizokami, Atsushi; Namiki, Mikio; Nakamoto, Masaru; Ooi, Akishi

    2015-01-01

    Neural epidermal growth factor-like like (NELL) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL1 and functions of NELL2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL1 and NELL2 in renal cell carcinoma (RCC) using clinical specimens and cell lines. We show that, whereas NELL1 and NELL2 proteins are strongly expressed in renal tubules in non-cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas. Silencing of NELL1 and NELL2 mRNA expression was also detected in RCC cell lines. Analysis of NELL1/2 promoter methylation status indicated that the CpG islands in the NELL1 and NELL2 genes are hypermethylated in RCC cell lines. NELL1 and NELL2 bind to RCC cells, suggesting that these cells express a receptor for NELL1 and NELL2 that can transduce signals. Furthermore, we found that both NELL1 and NELL2 inhibit RCC cell migration, and NELL1 further inhibits RCC cell adhesion. These results suggest that silencing of NELL gene expression by promoter hypermethylation plays roles in RCC progression by affecting cancer cell behavior. PMID:25726761

  13. The Renal Protective Effect of Jiangya Tongluo Formula, through Regulation of Adrenomedullin and Angiotensin II, in Rats with Hypertensive Nephrosclerosis

    PubMed Central

    Han, Lin; Ma, Yan; Qin, Jian-guo; Li, Li-na; Gao, Yu-shan; Zhang, Xiao-yu; Guo, Yi; Song, Lin-mei; Luo, Yan-ni; Chi, Xiao-yi

    2015-01-01

    We investigated the effect of Jiangya Tongluo (JYTL) formula on renal function in rats with hypertensive nephrosclerosis. A total of 21 spontaneously hypertensive rats (SHRs) were randomized into 3 groups: valsartan (10 mg/kg/d valsartan), JYTL (14.2 g/kg/d JYTL), and a model group (5 mL/kg/d distilled water); Wistar Kyoto rats comprised the control group (n = 7, 5 mL/kg/d distilled water). Treatments were administered by gavage every day for 8 weeks. Blood pressure, 24-h urine protein, pathological changes in the kidney, serum creatinine, and blood urea nitrogen (BUN) levels were estimated. The contents of adrenomedullin (ADM) and angiotensin II (Ang II) in both the kidney and plasma were evaluated. JYTL lowered BP, 24-h urine protein, serum creatinine, and BUN. ADM content in kidneys increased and negatively correlated with BP, while Ang II decreased and negatively correlated with ADM, but there was no statistically significant difference of plasma ADM between the model and the treatment groups. Possibly, activated intrarenal renin-angiotensin system (RAS) plays an important role in hypertensive nephrosclerosis and the protective function of ADM via local paracrine. JYTL may upregulate endogenous ADM level in the kidneys and antagonize Ang II during vascular injury by dilating renal blood vessels. PMID:26557147

  14. The Long-Term Effects of Prematurity and Intrauterine Growth Restriction on Cardiovascular, Renal, and Metabolic Function

    PubMed Central

    Chan, Patricia Y. L.; Morris, Jonathan M.; Leslie, Garth I.; Kelly, Patrick J.; Gallery, Eileen D. M.

    2010-01-01

    Objective. To determine relative influences of intrauterine growth restriction (IUGR) and preterm birth on risks of cardiovascular, renal, or metabolic dysfunction in adolescent children. Study Design. Retrospective cohort study. 71 periadolescent children were classified into four groups: premature small for gestational age (SGA), premature appropriate for gestational age (AGA), term SGA, and term AGA. Outcome Measures. Systolic blood pressure (SBP), augmentation index (Al), glomerular filtration rate (GFR) following protein load; plasma glucose and serum insulin levels. Results. SGA had higher SBP (average 4.6 mmHg) and lower GFR following protein load (average 28.5 mL/min/1.73 m2) than AGA. There was no effect of prematurity on SBP (P = .4) or GFR (P = .9). Both prematurity and SGA were associated with higher AI (average 9.7%) and higher serum insulin levels 2 hr after glucose load (average 15.5 mIU/L) than all other groups. Conclusion. IUGR is a more significant risk factor than preterm birth for later systolic hypertension and renal dysfunction. Among children born preterm, those who are also SGA are at increased risk of arterial stiffness and metabolic dysfunction. PMID:21197428

  15. Effect of Hydroxyurea Treatment on Renal Function Parameters: Results from the Multi-Center Placebo-Controlled BABY HUG Clinical Trial for Infants with Sickle Cell Anemia

    PubMed Central

    Alvarez, Ofelia; Miller, Scott T.; Wang, Winfred C.; Luo, Zhaoyu; McCarville, M. Beth; Schwartz, George J.; Thompson, Bruce; Howard, Thomas; Iyer, Rathi V.; Rana, Sohail R.; Rogers, Zora R.; Sarnaik, Sharada A.; Thornburg, Courtney D.; Ware, Russell E.

    2012-01-01

    Background Children with sickle cell anemia (SCA) often develop hyposthenuria and renal hyperfiltration at an early age, possibly contributing to the glomerular injury and renal insufficiency commonly seen later in life. The Phase III randomized double-blinded Clinical Trial of Hydroxyurea in Infants with SCA (BABY HUG) tested the hypothesis that hydroxyurea can prevent kidney dysfunction by reducing hyperfiltration. Procedure 193 infants with SCA (mean age 13.8 months) received hydroxyurea 20 mg/kg/day or placebo for 24 months. 99mTc diethylenetriaminepentaacetic acid (DTPA) clearance, serum creatinine, serum cystatin C, urinalysis, serum and urine osmolality after parent-supervised fluid deprivation, and renal ultrasonography were obtained at baseline and at exit to measure treatment effects on renal function. Results At exit children treated with hydroxyurea had significantly higher urine osmolality (mean 495 mOsm/kg H2O compared to 452 in the placebo group, p=0.007) and a larger percentage of subjects taking hydroxyurea achieved urine osmolality >500 mOsm/kg H2O. Moreover, children treated with hydroxyurea had smaller renal volumes (p=0.007). DTPA-derived glomerular filtration rate (GFR) was not significantly different between the two treatment groups, but was significantly higher than published norms. GFR estimated by the Chronic Kidney Disease in Children Schwartz formula was the best non-invasive method to estimate GFR in these children, as it was the closest to the DTPA-derived GFR. Conclusion Treatment with hydroxyurea for 24 months did not influence GFR in young children with SCA. However, hydroxyurea was associated with better urine concentrating ability and less renal enlargement, suggesting some benefit to renal function. PMID:22294512

  16. Evolution of Planetary Ice-Ocean Systems: Effects of Salinity

    NASA Astrophysics Data System (ADS)

    Allu Peddinti, D.; McNamara, A. K.

    2015-12-01

    Planetary oceanography is enjoying renewed attention thanks to not only the detection of several exoplanetary ocean worlds but also due to the expanding family of ocean worlds within our own star system. Our solar system is now believed to host about nine ocean worlds including Earth, some dwarf planets and few moons of Jupiter and Saturn. Amongst them, Europa, like Earth is thought to have an ice Ih-liquid water system. However, the thickness of the Europan ice-ocean system is much larger than that of the Earth. The evolution of this system would determine the individual thicknesses of the ice shell and the ocean. In turn, these thicknesses can alter the course of evolution of the system. In a pure H2O system, the thickness of the ice shell would govern if heat loss occurs entirely by conduction or if the shell begins to convect as it attains a threshold thickness. This switch between conduction-convection regimes could determine the longevity of the subsurface ocean and hence define the astrobiological potential of the planetary body at any given time. In reality, however, the system is not pure water ice. The detected induced magnetic field infers a saline ocean layer. Salts are expected to act as an anti-freeze allowing a subsurface ocean to persist over long periods but the amount of salts would determine the extent of that effect. In our current study, we use geodynamic models to examine the effect of salinity on the evolution of ice-ocean system. An initial ocean with different salinities is allowed to evolve. The effect of salinity on thickness of the two layers at any time is examined. We also track how salinity controls the switch between conductive-convective modes. The study shows that for a given time period, larger salinities can maintain a thick vigorously convecting ocean while the smaller salinities behave similar to a pure H2O system leading to a thick convecting ice-shell. A range of salinities identified can potentially predict the current state

  17. Use of urinary renal biomarkers to evaluate the nephrotoxic effects of melamine or cyanuric acid in non-pregnant and pregnant rats.

    PubMed

    Bandele, O J; Stine, C B; Ferguson, M; Black, T; Olejnik, N; Keltner, Z; Evans, E R; Crosby, T C; Reimschuessel, R; Sprando, R L

    2014-12-01

    Although traditional assessments of renal damage detect loss of kidney function, urinary renal biomarkers are proposed to indicate early changes in renal integrity. The recent adulteration of infant formula and other milk-based foods with melamine revealed a link between melamine ingestion and nephropathy. Thus, the effects of melamine and related analogs (e.g., cyanuric acid) should be assessed in other potentially sensitive groups. We evaluated whether urinary Kim-1, clusterin, and osteopontin could detect the effects of high doses of melamine or cyanuric acid in pregnant and non-pregnant female rats gavaged with 1000 mg/kg bw/day for 10 days. We demonstrate that these biomarkers can differentiate the severity of effects induced by melamine or cyanuric acid. All melamine-treated animals experienced adverse effects; however, pregnant rats were most sensitive as indicated by increased SCr, BUN, and kidney weights, decreased body weight, and presence of renal crystals. These effects coincided with elevated urinary biomarker levels as early as day 2 of exposure. One cyanuric acid-treated rat displayed effects similar to melamine, including increased urinary biomarker levels. This work illustrates that these biomarkers can detect early effects of melamine or cyanuric acid crystal-induced nephropathy and further supports the use of urinary protein immunoassays as a powerful, non-invasive method to assess nephrotoxicity. PMID:25455896

  18. Caerulein and morphine in a model of visceral pain. Effects on the hypotensive response to renal pelvis distension in the rat.

    PubMed

    Brasch, H; Zetler, G

    1982-05-01

    In pentobarbital-anaesthetized rats (60 mg/kg, i.p.) renal pelvis distension with a pressure of 80 cm H2O caused a decline in mean arterial blood pressure. This pressure response, which disappeared rapidly after cessation of the distension, was used to study the effects of analgesic drugs known to be effective in renal colic pain in man. Morphine (0.75 and 1 mg/kg, s.c.) and the decapeptide caerulein (1.6, 4 and 8 microgram/kg, s.c.) abolished the pressure response. The effects of the largest doses lasted for at least 30 min. Ineffective in this respect were (a) desulphated caerulein (40 microgram/kg, s.c.) and (b) additional doses of pentobarbital (20 and 40 mg/kg, s.c.). This shows (a) the importance of the sulphated tyrosine (known from previous studies on central effects) and (b) the missing influence of the depth of anaesthesia. Naloxone (0.5 mg/kg, s.c.) abolished the effect of morphine (1 mg/kg, s.c.) but failed to influence that of caerulein (8 microgram/kg, s.c.). Even a fourfold dose of naloxone (2 mg/kg, s.c.) did not weaken the effect of caerulein. Naloxone, per se, was ineffective. These results suggest different mechanisms of the present effects of morphine and caerulein. It appears that renal pelvis distension in the anaesthetized rat can serve as a model of renal colic. PMID:7110376

  19. Mother Knows Best: Epigenetic Inheritance, Maternal Effects, and the Evolution of Human Intelligence

    ERIC Educational Resources Information Center

    Bjorklund, David F.

    2006-01-01

    Contemporary evolution biology has recognized the role of development in evolution. Evolutionarily oriented psychologists have similarly recognized the role that behavioral plasticity, particularly early in development, may have had on the evolution of species, harking back to the ideas of Baldwin (the Baldwin effect). Epigenetic theories of…

  20. Mutational effects on stability are largely conserved during protein evolution.

    PubMed

    Ashenberg, Orr; Gong, L Ian; Bloom, Jesse D

    2013-12-24

    Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation. PMID:24324165

  1. Effects of D-glucose, 2-deoxy-D-glucose and D-xylose on renal function in the rat.

    PubMed Central

    Garland, H O; Singh, H J

    1988-01-01

    1. Standard renal clearance techniques were used to investigate the effects of 2.5, 5 and 10% D-glucose, 2.5% 2-deoxy-D-glucose and 2.5% D-xylose on kidney function in male rats. 2. There was no consistent effect of D-glucose on urinary sodium output except with 10% D-glucose, where sodium excretion was raised compared to controls. 3. An increased urinary calcium output was seen in all D-glucose-infused rats compared to controls. Values obtained for 2.5, 5 and 10% glucose were respectively 32, 61 and 58% above control data. Neither 2-deoxy-D-glucose nor D-xylose produced a calciuresis. 4. The increased urinary calcium excretion in D-glucose rats was the result of a reduction in fractional calcium reabsorption. Glomerular filtration rate (GFR) was unchanged. It was not dependent upon glycosuria or a diuresis. PMID:3418534

  2. Renal Replacement Therapy.

    PubMed

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients' clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the "Tower of Babel" of critical care nephrology. PMID:26918174

  3. Renal Replacement Therapy

    PubMed Central

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology. PMID:26918174

  4. Renal denervation and hypertension.

    PubMed

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  5. Thermal evolution of Mercury: Effects of volcanic heat-piping

    NASA Astrophysics Data System (ADS)

    Multhaup, K.

    2009-09-01

    A 1D thermal evolution model of Mercury is presented. It accounts for stagnant lid convection, mantle differentiation and inner core growth. Early MESSENGER results indicate that—contrary to prior conclusions drawn from Mariner 10 imagery—volcanism has indeed played a significant role in Mercury's past. To study the effects of mantle heat bypassing the stagnant lid by means of volcanic heat-piping, contrasting end-member models are considered. Results show how break-down of mantle convection and onset of inner core growth are influenced by the mode of heat removal. Structural models of present day Mercury are presented. Their dependence on the core sulphur contents predominates that on the choice of mantle heat removal. However, the latter clearly controls the timing of thermal history events.

  6. The Mozart effect: tracking the evolution of a scientific legend.

    PubMed

    Bangerter, Adrian; Heath, Chip

    2004-12-01

    Theories of the diffusion of ideas in social psychology converge on the assumption that shared beliefs (e.g., social representations, rumours and legends) propagate because they address the needs or concerns of social groups. But little empirical research exists demonstrating this link. We report three media studies of the diffusion of a scientific legend as a particular kind of shared belief. We studied the Mozart effect (ME), the idea that listening to classical music enhances intelligence. Study 1 showed that the ME elicited more persistent media attention than other science reports and this attention increased when the ME was manifested in events outside of science. Study 2 suggested that diffusion of the ME may have responded to varying levels of collective anxiety. Study 3 demonstrated how the content of the ME evolved during diffusion. The results provide evidence for the functionality of diffusion of ideas and initial elements for a model of the emergence and evolution of scientific legends. PMID:15601511

  7. Renal Denervation

    PubMed Central

    Pan, Tao; Guo, Jin-he; Teng, Gao-jun

    2015-01-01

    Abstract Type 2 diabetes mellitus (T2DM) is a group of metabolic diseases of multiple etiologies. Although great progress has been made, researchers are still working on the pathogenesis of T2DM and how to best use the treatments available. Aside from several novel pharmacological approaches, catheter-based sympathetic renal denervation (RDN) has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. In this article, we will summarize herein the role sympathetic activation plays in the progression of T2DM and review the recent clinical RDN experience in glucose metabolism. We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2015. Studies were included if a statistical relationship was investigated between RDN and T2DM. The quality of each included study was assessed by Newcastle–Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did meta-regression analysis. Finally, we identified 4 eligible articles. In most studies, RDN achieved via novel catheter-based approach using radiofrequency energy has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. But the DREAMS-Study showed that RDN did not change median insulin sensitivity nor systemic sympathetic activity. Firstly, the current published studies lacked a proper control group, along with the sample capacity was small. Also, data obtained in the subgroups of diabetic patients were not separately analyzed and the follow-up period was very short. In addition, a reduction in blood pressure accounts for the improvements in glucose metabolism and insulin resistance cannot be excluded. If the favorable result of better glucose metabolism is confirmed in large-scale, randomized studies

  8. Effect of Chronic Bile Duct Obstruction on Renal Handling of Salt and Water

    PubMed Central

    Better, Ori S.; Massry, Shaul G.

    1972-01-01

    Renal sodium reabsorption and the concentrating and diluting abilities of the kidney were evaluated in the same trained mongrel dogs before and after chronic common bile duct ligation (BDL). Glomerular filtration rate (GFR) and CPAH were not altered by BDL. The natriuretic response to a standardized infusion of 0.45% solution of NaCl was markedly blunted by BDL (P < 0.01); calculated distal sodium delivery was significantly less in experiments after BDL than in control studies. Furthermore, the fractional reabsorption of sodium at the diluting segment for any given rate of distal delivery was enhanced by BDL. Similarly, CH2O/100 ml GFR for a given sodium delivery was higher after BDL than control values. Maximal urinary concentration (Uosm-max) was lower after BDL, and the mean Uosm-max for the whole group of animals was 60% of the control value (P < 0.001). Mean maximal TH2O/100 ml GFR after BDL was not different from control values; however, TcH2O/100 ml GFR for a given Cosm/100 ml GFR was lower after BDL in three dogs only. The sodium content of the inner part of renal medulla after BDL was significantly lower than the values obtained in control animals. The excretion of an oral water load in the conscious state was impaired after BDL; although all animals excreted hypotonic urine, urinary osmolality was usually higher after BDL than in control studies. Maximal urinary concentration and the excretion of an oral water load were not affected by sham operation. These studies demonstrate that chronic, common bile duct ligation is associated with (a) enhanced sodium reabsorption both in the proximal and diluting segments of the nephron, (b) a defect in attaining maximal urinary concentration, (c) diminished sodium content in the renal papilla, and (d) impaired excretion of a water load. The results suggest that decreased distal delivery of sodium may underlie the abnormality in the concentrating mechanism and in the inability to normally excrete a water load. In

  9. Effect of mitochondrial potassium channel on the renal protection mediated by sodium thiosulfate against ethylene glycol induced nephrolithiasis in rat model

    PubMed Central

    Baldev, N.; Sriram, R.; Prabu, P.C.; Gino, A. Kurian

    2015-01-01

    ABSTRACT Purpose: Sodium thiosulfate (STS) is clinically reported to be a promising drug in preventing nephrolithiasis. However, its mechanism of action remains unclear. In the present study, we investigated the role of mitochondrial KATP channel in the renal protection mediated by STS. Materials and Methods: Nephrolithiasis was induced in Wistar rats by administrating 0.4% ethylene glycol (EG) along with 1% ammonium chloride for one week in drinking water followed by only 0.75% EG for two weeks. Treatment groups received STS, mitochondrial KATP channel opener and closer exclusively or in combination with STS for two weeks. Results: Animals treated with STS showed normal renal tissue architecture, supported by near normal serum creatinine, urea and ALP activity. Diazoxide (mitochondria KATP channel opening) treatment to the animal also showed normal renal tissue histology and improved serum chemistry. However, an opposite result was shown by glibenclamide (mitochondria KATP channel closer) treated rats. STS administered along with diazoxide negated the renal protection rendered by diazoxide alone, while it imparted protection to the glibenclamide treated rats, formulating a mitochondria modulated STS action. Conclusion: The present study confirmed that STS render renal protection not only through chelation and antioxidant effect but also by modulating the mitochondrial KATP channel for preventing urolithiasis. PMID:26742969

  10. Disorder effects in the evolution from BCS to BEC superfluidity

    NASA Astrophysics Data System (ADS)

    Han, Li; de Melo, Carlos A. R. Sa

    2009-03-01

    We discuss the effects of disorder on the critical temperature of superfluids during the evolution from BCS to BEC. For s-wave superfluids we find that the critical temperature is weakly affected by disorder in the BCS regime as described in Anderson’s theorem, even less affected by disorder at zero chemical potential (near unitarity), but strongly affected by disorder in the BEC regime, where Anderson's theorem does not apply. This suggests that the superfluid is more robust to the effects of disorder at the interaction parameter where the chemical potential vanishes (close to unitarity). We construct a three dimensional phase diagram of critical temperature, disorder and interaction parameter [1], and show that there are regions of localized superfluidity, as well as insulating regions due to Anderson localization of fermions (BCS regime) and molecular bosons (BEC regime). The phase diagram for higher angular momentum (e.g. p-wave and d-wave) is also analyzed, where the effects of disorder are much more dramatic in the BCS regime in comparison to the s-wave case because pair breaking is strong, while the disorder effects in BEC regime are similar to what occurs in the s-wave case. [1] Li Han, C. A. R. Sa de Melo, arXiv:0812.xxxx

  11. The effect of perinatal taurine on adult renal function does not appear to be mediated by taurine’s inhibition of the renin-angiotensin system

    PubMed Central

    Roysommuti, Sanya; Kritsongsakchai, Angkana; Wyss, J. Michael

    2016-01-01

    This study tests the hypothesis that perinatal taurine supplementation alters adult renal function by inhibition of the renin-angiotensin system. Female Sprague-Dawley rats were fed normal rat chow and given water alone (Control) or water containing an angiotensin converting enzyme inhibitor (captopril, 400 mg/ml) from conception until delivery (FD) or from delivery until weaning (LD). After weaning, the rats received normal rat chow and tap water. At 7–8 weeks of age, renal function at rest and after acute saline load was studied in conscious, restrained male rats. Body weight, mean arterial pressure, heart rate, effective renal blood flow, and renal vascular resistance were not significantly different among the three groups. Compared to Control, glomerular filtration rate, but not filtration fraction, significantly increased after saline load in both FD and LD groups. Water excretion significantly increased only in FD compared to Control, while fractional water excretion was significantly increased after saline load in both FD and LD groups. Sodium excretion significantly increased after saline load only in FD, while both captopril-treated groups significantly decreased fractional sodium excretion. Potassium excretion significantly increased in both FD and LD groups, while fractional potassium excretion significantly increased at rest in FD and decreased in LD groups after saline load. These effects of perinatal RAS inhibition on adult renal function contrast sharply, and are opposite in many cases to, the effects of perinatal taurine supplementation. Thus, these data suggest that perinatal taurine supplementation does not alter adult renal function through its ability to inhibit the perinatal RAS. PMID:25833535

  12. Deceased donor renal transplantation and the disruptive effect of commercial transplants: the experience of Oman.

    PubMed

    Mohsin, N; Al-Busaidy, Q; Al-Marhuby, H; Al-Lawati, J; Daar, A S

    2014-01-01

    The Oman Renal Transplantation Program was established in 1988 as a joint venture between Sultan Qaboos University and the Ministry of Health. It began with both living related donor (LRD) and deceased donor (DD) transplants. Over the next nine years, while the LRD programme progressed relatively well, there were only thirteen DD transplants. Two of the DD kidneys were obtained from overseas via an active collaboration with the Euro-transplant organisation, and one DD kidney was obtained from Saudi Arabia within the Gulf Cooperative Council exchange programme. The rest of the DD kidneys were obtained in Oman. The Omani DD programme, although it was a pioneering effort in the Gulf region at the time, was not entirely sustainable. In this paper we focus on the challenges we encountered. Among the major challenges was the absence of resources to establish a dedicated DD programme and particularly the failure to develop a cadre of dedicated transplant coordinators. PMID:25160966

  13. Evaluation of the effect of dietary lycopene, the main carotenoid in tomato (Lycopersicon esculentum), on the in vivo renal reducing ability by a radiofrequency electron paramagnetic resonance method.

    PubMed

    Yoshida, Kazutaka; Yokoyama, Hidekatsu; Oteki, Takaaki; Matsumoto, Gaku; Aizawa, Koichi; Inakuma, Takahiro

    2011-04-13

    Although it has been reported that dietary lycopene, the main carotenoid in tomato, improved drug-induced nephropathy, there are no reports on the effect of orally administered lycopene on the in vivo renal reducing (i.e., antioxidant) ability. The radiofrequency electron paramagnetic resonance (EPR) method is a unique technique by which the in vivo reducing ability of an experimental animal can be studied. In this study, the in vivo changes in the renal reducing ability of rats orally administered lycopene were investigated using a 700 MHz EPR spectrometer equipped with a surface-coil-type resonator. Rats were fed either a control diet or a diet containing lycopene. After 2 weeks, in vivo EPR measurements were conducted. The renal reducing ability of lycopene-treated rats was significantly greater than that of the control. This is the first verification of in vivo antioxidant enhancement via dietary lycopene administration. PMID:21381743

  14. Local renal ischemia during burn shock in rat effected by thromboxane A2 and serotonin.

    PubMed

    Haugan, A; Kirkebø, A

    1986-01-01

    Intermittent patchy ischemia in the renal cortex during traumatic shock has previously been observed in dogs and rats. In recent experiments on rats a high rate of abrupt changes in local blood flow was observed after scalding. To try to reveal endogenous factors causing such ischemic episodes, we scalded six series of anesthetized rats (50% of body surface for 30 s in 80 degrees C water) and measured arterial pressure (AP), hematocrit (Hct), and local renal cortical blood flow (RCF). RCF was recorded by the local H2 washout technique. After scalding, RCF decreased markedly in all series whereas AP was relatively well preserved. In accordance with previous experiments, 11% of the washout curves recorded 0-75 min after scalding showed abrupt changes in local blood flow, rising to 27% during the next 60 min in drug-untreated rats. In contrast, blocking of serotonin S2 receptors with Ketanserin abolished the phenomenon. However, in rats treated with the prostaglandin synthesis blockers, indomethacin (general) or 3-ethyl pyridin (thromboxane A2 blocker), the phenomenon was observed in only 2-3% of the washout curves. Furthermore, after blocking the AngII receptors by saralasin or alpha receptors by phentolamine in separate series, the frequency of abrupt flow shifts was reduced in comparison to the frequency in untreated rats. The results indicate that intermittent, patchy vasoconstriction is mediated by serotonin and thromboxane A2 (TxA2), probably released from platelets. The occurrence of ischemic episodes also depends on the local AngII and alpha-adrenergic tonus present after scalding. PMID:3021355

  15. The Dose-Dependent Effect of Nesiritide on Renal Function in Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Xiong, Bo; Wang, Chunbin; Yao, Yuanqing; Huang, Yuwen; Tan, Jie; Cao, Yin; Zou, Yanke; Huang, Jing

    2015-01-01

    Background Conflicting renal effects of nesiritide have been reported in patients with acute decompensated heart failure. To answer this controversy, we performed a meta-analysis of randomized controlled trials to evaluate the influence of nesiritide on renal function in patients with acute decompensated heart failure. Methods Articles were obtained from PubMed, Medline, Cochrane Library and reference review. Randomized controlled studies that investigated the effects of continuous infusion of nesiritide on renal function in adult patients with acute decompensated heart failure were included and analyzed. Fixed-effect model was used to estimate relative risk (RR) and weight mean difference (WMD). The quality assessment of each study, subgroup, sensitivity, and publication bias analyses were performed. Results Fifteen randomized controlled trials were eligible for inclusion. Most of included studies had relatively high quality and no publication bias was found. Overall, compared to control therapies, nesiritide might increase the risk of worsening renal function in patients with acute decompensated heart failure (RR 1.08, 95% CI 1.01–1.15, P = 0.023). In subgroup analysis, high-dose nesiritide strongly associated with renal dysfunction (RR 1.54, 95% CI 1.19-2.00, P = 0.001), but no statistical differences were observed in standard-dose (RR 1.04, 95% CI 0.98-1.12, P = 0.213), low-dose groups (RR 1.01, 95% CI 0.74-1.37, P = 0.968) and same results were identified in the subgroup analysis of placebo controlled trials. Peak mean change of serum creatinine from baseline was no significant difference (WMD -2.54, 95% CI -5.76-0.67, P = 0.121). Conclusions In our meta-analysis, nesiritide may have a dose-dependent effect on renal function in patients with acute decompensated heart failure. High-dose nesiritide is likely to increase the risk of worsening renal function, but standard-dose and low-dose nesiritide probably have no impact on renal function. These findings

  16. Renal effects of Mammea africana Sabine (Guttiferae) stem bark methanol/methylene chloride extract on L-NAME hypertensive rats

    PubMed Central

    Nguelefack-Mbuyo, Elvine Pami; Dimo, Théophile; Nguelefack, Télesphore Benoit; Dongmo, Alain Bertrand; Kamtchouing, Pierre; Kamanyi, Albert

    2010-01-01

    Objective: The present study aims at evaluating the effects of methanol/methylene chloride extract of the stem bark of Mammea africana on the renal function of L-NAME treated rats. Material and Methods: Normotensive male Wistar rats were divided into five groups respectively treated with distilled water, L-NAME (40 mg/kg/day), L-NAME + L-arginine (100 mg/kg/day), L-NAME + captopril (20 mg/kg/day) or L-NAME + M. africana extract (200 mg/kg/day) for 30 days. Systolic blood pressure was measured before and at the end of treatment. Body weight was measured at the end of each week. Urine was collected 6 and 24 h after the first administration and further on day 15 and 30 of treatment for creatinine, sodium and potassium quantification, while plasma was collected at the end of treatment for the creatinine assay. ANOVA two way followed by Bonferonni or one way followed by Tukey were used for statistical analysis. Results: M. africana successfully prevented the rise in blood pressure and the acute natriuresis and diuresis induced by L-NAME. When given chronically, the extract produced a sustained antinatriuretic effect, a non-significant increase in urine excretion and reduced the glomerular hyperfiltration induced by L-NAME. Conclusions: The above results suggest that the methanol/methylene chloride extract of the stem bark of M. africana may protect kidney against renal dysfunction and further demonstrate that its antihypertensive effect does not depend on a diuretic or natriuretic activity. PMID:20927244

  17. Exocyst Sec10 protects renal tubule cells from injury by EGFR/MAPK activation and effects on endocytosis

    PubMed Central

    Fogelgren, Ben; Zuo, Xiaofeng; Buonato, Janine M.; Vasilyev, Aleksandr; Baek, Jeong-In; Choi, Soo Young; Chacon-Heszele, Maria F.; Palmyre, Aurélien; Polgar, Noemi; Drummond, Iain; Park, Kwon Moo; Lazzara, Matthew J.

    2014-01-01

    Acute kidney injury is common and has a high mortality rate, and no effective treatment exists other than supportive care. Using cell culture models, we previously demonstrated that exocyst Sec10 overexpression reduced damage to renal tubule cells and speeded recovery and that the protective effect was mediated by higher basal levels of mitogen-activated protein kinase (MAPK) signaling. The exocyst, a highly-conserved eight-protein complex, is known for regulating protein trafficking. Here we show that the exocyst biochemically interacts with the epidermal growth factor receptor (EGFR), which is upstream of MAPK, and Sec10-overexpressing cells express greater levels of phosphorylated (active) ERK, the final step in the MAPK pathway, in response to EGF stimulation. EGFR endocytosis, which has been linked to activation of the MAPK pathway, increases in Sec10-overexpressing cells, and gefitinib, a specific EGFR inhibitor, and Dynasore, a dynamin inhibitor, both reduce EGFR endocytosis. In turn, inhibition of the MAPK pathway reduces ligand-mediated EGFR endocytosis, suggesting a potential feedback of elevated ERK activity on EGFR endocytosis. Gefitinib also decreases MAPK signaling in Sec10-overexpressing cells to levels seen in control cells and, demonstrating a causal role for EGFR, reverses the protective effect of Sec10 overexpression following cell injury in vitro. Finally, using an in vivo zebrafish model of acute kidney injury, morpholino-induced knockdown of sec10 increases renal tubule cell susceptibility to injury. Taken together, these results suggest that the exocyst, acting through EGFR, endocytosis, and the MAPK pathway is a candidate therapeutic target for acute kidney injury. PMID:25298525