[Evaluation of risk factors and prognosis on diodone-induced acute kidney injury according to ESUR and KDIGO criteria].

OBJECTIVE: To investigate the incidence, risk factors and prognosis for contrast-induced acute kidney injury (CI-AKI) according to ESUR and KDIGO criteria in patients undergoing angiography.
 METHODS: We evaluated 260 patients undergoing angiography and/or intervention therapy from April 2011 to January 2012 in the Second Xiangya Hospital of Central South University. All patients received low-osmolality contrast agent (ioversol). Serum creatinine was measured before angiography or at 48 or 72 h after procedure. The multivariate logistic regression was used to analyze the risk factors of CI-AKI. The major adverse events were observed in a year of follow-up.
 RESULTS: Among the 260 patients, 23 experienced CI-AKI and the incidence was 8.8% according to ESUR criteria. Twelve patients experienced CI-AKI and the incidence was 4.6% according to KDIGO criteria. The multivariate logistic regression analysis showed that diabetes mellitus and dehydration were the independent risk factors for CI-AKI according to ESUR criteria; In another KDIGO criteria, chronic kidney disease (CKD), hypercholesterolemia and diabetes mellitus were the independent risk factors for CI-AKI. The prognosis study showed that the mortality of patients with CI-AKI were significantly higher than those without CI-AKI (P<0.05).
 CONCLUSION: The incidence of CI-AKI is associated with diagnostic criteria. Diabetes mellitus, CKD, dehydration and hypercholesterolemia were the independent risk factors for CI-AKI. CI-AKI is a relevant factor for mortality in a year after angiography and/or intervention therapy.

Coumarin-based, electron-trapping iridium complexes as highly efficient and stable phosphorescent emitters for organic light-emitting diodes.

A new class of coumarin-based iridium tris-cyclometalated complexes has been developed. These complexes are highly emissive, with emission colors ranging from green to orange-red. Besides modification of ligand structures, color tuning was realized by incorporation of ligands with different electrochemical properties in a heteroleptic structure. The organic light-emitting diodes (OLEDs) using these compounds as emissive dopants are highly efficient and stable. Unlike other Ir(III) phosphorescent dopants, these coumarin-based Ir(III) dopants can effectively trap and transport electrons in the emissive layer.

Transport of 99mTc-MAG3 via rat renal organic anion transporter 1.

UNLABELLED: Recently, complementary DNA (cDNA) encoding a p-aminohippurate (PAH) transporter designated rat organic anion transporter 1 (OAT1) was isolated. OAT1, a multispecific organic anion transporter at the basolateral membrane, is exclusively expressed in the middle segment of the proximal tubule in the rat kidney. It has been proposed that OAT1 is indirectly involved in PAH uptake via the Na(+) dicarboxylate cotransporter. In this study, in molecular biologic experiments using OAT1-expressing Xenopus laevis oocytes, we obtained evidence that (99m)Tc-mercaptoacetylglycylglycylglycine (MAG3) is transported via OAT1. METHODS: Capped OAT1 complementary RNA (cRNA) was synthesized from library plasmid cDNA linearized with BamHI using in vitro transcription. Defolliculated oocytes were injected with 10 ng of OAT1 cRNA. Two to 3 d after injection, uptake of (99m)Tc-MAG3 was measured using ND96 solution containing 18.5 kBq of (99m)Tc-MAG3. Before the uptake experiments, OAT1-expressing oocytes were preincubated for 2 h with 1 mmol/L glutarate (a dicarboxylate), to generate an outwardly directed glutarate gradient. Then, after incubation for 60 min at room temperature, radioactivity of oocytes was determined. For the inhibition experiments, uptake was assessed in the absence or presence of inhibitor: 2 mmol/L of PAH, o-iodohippurate (OIH), probenecid, 3,5-diiodo-4-pyridone-N-acetate (iodopyracet), furosemide, ethacrynic acid, glucoheptonate, maleic acid, L-Tyr, or tetraethylammonium (TEA) or 0.1 mmol/L of 2,4-dinitrophenol (DNP). RESULTS: Na(+) had a significant effect on (99m)Tc-MAG3 uptake (P < 0.05). Accumulated glutarate stimulated simultaneous (99m)Tc-MAG3 uptake and glutarate excretion (P < 0.001). The following compounds significantly inhibited (99m)Tc-MAG3 uptake: PAH, 8.5% +/- 16.2% of (99m)Tc-MAG3 uptake in the absence of an inhibitor; OIH, 26.4% +/- 21.7%; probenecid, 29.1% +/- 12.4%; iodopyracet, 15.8% +/- 7.9%; furosemide, 30.5% +/- 15.7%; ethacrynic acid, 21.6% +/- 10.6%; glucoheptonate, 35.6% +/- 22.6%; and maleic acid, 60.1% +/- 18.7%. (99m)Tc-MAG3 accumulation in Xenopus laevis oocytes was not significantly inhibited by TEA, L-Tyr, or DNP. CONCLUSION: The following substances had a cis-inhibitory effect on (99m)Tc-MAG3 transport: PAH, OIH, probenecid, iodopyracet, furosemide, ethacrynic acid, and glucoheptonate. Glutarate had a trans-stimulative effect on (99m)Tc-MAG3 transport. (99m)Tc-MAG3 acts as a substrate of OAT1, an organic anion/dicarboxylate exchanger.

[The effect of cimetidine on the renal excretion of verografin and iodamide in dogs]. / Vliianie tsimetidina na pochechnuiu ékskretsiiu verografina i iodamida u sobak.

The intravenous injection of cimetidine in a dose of 20 mg/kg enhanced verografine and iodamide excretion in chronic canine experiments. The higher verografine and iodamide excretion was due to their increased renal tubular secretion. In dogs, cimetidine unchanged the secretion of cardiotrast, a test agent for anionic transport. Possible extrarenal mechanisms of action of cimetidine on verografine and iodamide transport were also examined.

Effect of iodopyracet on renal excretion of sulfamethizole in rabbits.

To predict quantitatively drug interaction kinetics from the single-drug clearance studies, we examined the effect of iodopyracet (IOD) on sulfamethizole (SMZ) excretion in rabbits. Even though the decline of systemic IOD plasma concentration was linear, the renal clearance of SMZ decreased significantly in the presence of IOD. The results could be described by a perfusion model incorporated with the competitive inhibition for tubular secretion. For IOD with a high extraction ratio, it was suggested that a heavy load of the drug was supplied to the sites of secretion and caused the saturation of transport systems, even though the renal excretion kinetics were apparently linear in respect to the systemic circulation. These facts indicated that a linear relationship between the concentrations in the systemic circulation and at the sites of tubular secretion can not always be presumed. Consequently, SMZ-IOD interaction study stressed the importance of the drug concentrations at the sites of interaction for quantitative elucidation of drug-drug interactions.

Kinetic studies on drug disposition in rabbits. I. Renal excretion of iodopyracet and sulfamethizole.

In order to quantify the renal handling of iodopyracet (IOD) and sulfamethizole (SMZ), single-drug clearance studies in rabbits were performed under quasi-steady state conditions with stepwise increasing the infusion rate of IOD or SMZ. Although concentration dependence of plasma protein binding was observed for both drugs, the urinary excretion rate of IOD was proportional to its total plasma concentration at low total plasma concentrations of 0.05-0.8 mM. On the other hand, the relationship between urinary excretion rate and total plasma concentration of SMZ was a concave-ascending curve at low plasma concentrations and the renal clearance of SMZ was sensitive to changes in plasma protein binding. However, renal clearances referenced to unbound plasma concentration at total plasma concentrations of 0.05 mM for IOD and SMZ were 9.5 and 38 l/h, respectively. Those values were much greater than the effective plasma flow in rabbits. These facts indicated that the intrinsic clearances at the sites of tubular secretion were high and that the rates of secretion were fully or partially limited by the renal plasma flow. Furthermore it was suggested that unbound drug was liberated from plasma protein at the sites of tubular secretion. The data obtained at high plasma concentrations indicated that the tubular secretion of IOD had capacity limited characteristics and that the urinary excretion of SMZ involved tubular reabsorption as well as saturable tubular secretion. From the data obtained, a perfusion-limited pharmacokinetic model was constructed characterizing the excretory processes, namely, glomerular filtration, passive tubular reabsorption, saturable tubular secretion and reequilibrium between bound and unbound drugs in plasma. For both drugs, the estimates for bulk flow rate were reasonable values of effective renal plasma flow and the dissociation constants for tubular secretion agreed well with those for in vitro renal cortex accumulation, suggesting that the kinetic model based on physiological concepts was useful for the understanding of the drug elimination processes.

[The renal transport of cardiotrast, verografin and iodamide]. / Pochechnyi transport kardiotrasta, verografina i iodamida.

In chronic experiments on dogs it was shown that verografin and iodamide are excreted from the body not only by filtration but by tubular excretion as well. The maximal transport of verografin and iodamide is significantly lower than that of cardiotrast. In experiments on rats similar results were obtained. Concurrent administration of verografin and iodamide with cardiotrast decreases their excretion in the urine in rats that is probably due to competition for the common transport system in the epithelium of renal tubules.

[Effect of taktivin on diuresis and tubular cardiotrast secretion in the kidney]. / Vliianie taktivina na mocheotdelenie i kanal'tsevuiu sekretsiiu kardiotrasta v pochke.

The effect of a new immunomodulator taktivin (7-20 micrograms/kg subcutaneously, for 6 days) on the diuresis and tubular transport of cardiotrast (diodrast) was studied on rats. taktivin was shown to increase the tubular transport of the xenobiotic without significant changes in glomerular filtration and renal excretion of water, sodium, potassium, uric acid and creatinine. Possible mechanism of taktivin's action on the tubular transport of xenobiotics is discussed.

Physiologically based pharmacokinetic model for the renal clearance of iodopyracet and the interaction with probenecid in the dog.

Plasma kinetics and renal excretion of iodopyracet (3.0 g, administered i.v.) with and without concomitant administration of probenecid were studied in the beagle dog. Pharmacokinetic analysis revealed that tubular secretion is the predominant route of excretion, and that secretion is inhibited by probenecid. A physiologically based kidney model is proposed comprising all the functional characteristics of the kidney that determine the excretion of iodopyracet, i.e. renal plasma flow, urine flow, protein binding, glomerular filtration, tubular secretion, and tubular accumulation. The model enabled an accurate description and analysis of the measured plasma levels and renal excretion rates. Renal clearance of iodopyracet is characterized by supply-limited elimination at low plasma concentrations and capacity-limited elimination at high plasma levels. The interaction with probenecid could be adequately described with the model by competitive inhibition of the carrier-mediated uptake of iodopyracet into the tubular cells. Model calculations showed that in the control experiments tubular secretion was accompanied by a pronounced accumulation of iodopyracet within the cells, which was clearly diminished in the presence of probenecid.

[Tubular secretion of cardiotrast in the progeny of rats receiving it throughout pregnancy]. / Kan al'tsevaia sekretsiia kardiotrasta u potomstva krys, poluchavshikh ego na protiazhenii beremennosti.

Administration of cardiotrast (50-80 mg twice a day subcutaneously) during pregnancy was shown to induce a significant suppression of tubular secretion of the xenobiotic in the offspring. When cardiotrast was given only in the postnatal period, tolerance failed to develop.

[Effect of zixoryn on diuresis and renal transport of xenobiotics]. / Vliianie ziksorina na mocheotdelenie i transport ksenobiotikov v pochke.

A new inducer of the monooxygenase system zixoryn (oral dose--100 mg/kg, for 4 days) increased the excretion and maximum tubular transport of cardiotrast (diodrast) in rats. Zixoryn had no effect on daily and water diuresis and renal excretion of sodium, potassium and creatinine.

[Effect of 5-hydroxymethyluracil and dimephosphon on the tubular secretion of xenobiotics in the kidney]. / Vliianie 5-oksimetiluratsila i dimefosfona na kanal'tsevuiu sekretsiiu ksenobiotikov v pochke.

The effect of 5-hydroxymethyluracyl and dimephosphon on the tubular secretion of cardiotrast was studied on rats. The both drugs were shown to increase the tubular transport of xenobiotics.

[Characteristics of the granules formed in nucleated erythrocytes as affected by cardiotrast]. / Kharakteristika granul, obrazuiushchikhsia v iadernykh éritrotsitakh pod vliianiem kardiotrasta.

Numerous granules are formed in frog erythrocytes under the influence of cardiotrast (C) (diethanolamine-3,5-diiodo-4-pyridone-1-acetic acid). However, as revealed by cytospectrophotometric investigation and X-ray microanalysis, no C was accumulated in these granules. It is known that C can dissociate into diethanolamine and 3,5-diiodo-4-pyridone-1-acetic acid. It was assumed that under the influence of C granule formation may occur at the expense of an uncharged diethanolamine form penetrating into lysosome-like structures to be accumulated by protonation process. Diethanolamine was found to provoke granule formation in frog erythrocytes. It is impossible to reveal substance in granules because it is colourless and has no ultraviolet absorbtion band. Under the influence of some inhibitors of energy metabolism on granule formation and the granules formed, their inhibitory effect is exerted on the process of granule formation. In granules isolated by differential centrifugation activity of some marker lysosomal enzymes was found which enabled us to attribute these granules to lysosome-like structures.

[Effect of immunostimulants on kidney tubule secretion of xenobiotics]. / Vliianie immunostimuliatorov na kanal'tsevuiu sekretsiiu ksenobiotikov v pochke.

Excretion of cardiotrast (diotrast) was used to study tubular secretion of organic compounds in rats. Immunostimulants prodigiosin (0.05 mg/kg) and levamisole (10 mg/kg) injected subcutaneously three times every other day increased cardiotrast excretion. High levamisole dose (50 mg/kg), having no stimulating effect on the immunity, failed also to influence tubular cardiotrast transport. Possible mechanisms of immunostimulants' action on the tubular secretion of xenobiotics is discussed.

Radiocontrast-induced renal failure.

Review of the literature concerning contrast-induced renal dysfunction shows that the currently used agents are remarkably safe with careful patient selection. Clinically apparent kidney failure after their use is essentially nonexistent in those without preexistent renal insufficiency. The incidence rises rapidly in those with azotemia from any cause, however, and diabetic persons with nephropathy are perhaps at special risk. Vigorous volume expansion is possibly effective as a preventive measure and may attenuate adverse effects in those in whom postcontrast dysfunction occurs. New agents are becoming available. It is not yet known if these will prove safer or cost-effective. They have some experimentally demonstrated and theoretic advantages over the presently used agents.

Does a water soluble contrast enema assist in the management of acute large bowel obstruction: a prospective study of 117 cases.

We have performed a prospective study on 117 patients in order to assess the value of a single contrast water soluble enema in acute large bowel obstruction. In 99 cases where the plain films suggested a diagnosis of mechanical obstruction, the Diodone enema confirmed its presence in 52, and relocated its site in 11. There was free flow of contrast to the caecum in the remaining 35, 11 of whom were shown to have idiopathic pseudo-obstruction. The plain films suggested a diagnosis of pseudo-obstruction in 18 patients. The Diodone enema confirmed this diagnosis in 15, but revealed an unsuspected mechanical obstruction in two. The examination failed in two cases. We conclude that the water soluble single contrast enema is of value in the management of large bowel obstruction. It will confirm the diagnosis of mechanical obstruction and prevent unnecessary surgery in patients with pseudo-obstruction.

[Effect of dopamine on transport of organic substances in dog kidneys]. / Vliianie dofamina na transport organicheskikh veshchestv v pochkakh sobak.

I. v. infusion of dopamine increased diuresis, glomerular filtration rate, maximal reabsorption of glucose and tubular secretion of cardiotrast. Infusion of dopamine into the renal artery did not affect glomerular filtration rate and tubular secretion of cardiotrast while maximal reabsorption rate of glucose was increased. Dopamine exerted some direct effect on the transport of glucose, which effect can be blocked with haloperidol.