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Biomedical subjects

R Ranganathan

Publications and source records attributed to R Ranganathan.

48 records · Page 3Linked to original sources

Nonionic dimer: development and initial testing of an intrathecal contrast agent.

A nonionic dimer (DL-3-117) containing a novel substituent (D,L amino-threitol) was synthesized and tested as an intrathecal contrast medium. In the complement-mediated assay, the dimer was approximately half as inhibitory of hemolysis as metrizamide or iopamidol. The lethal dose (LD50) in protozoa was 320 mg I/ml for DL-3-117, 96 mg I/ml for metrizamide, and 101 mg I/ml for iopamidol. The intravenous LD50 of DL-3-117 in mice was 26 g/kg, and in rats it was 12.7 g/kg. The effective dose (ED50) of intradiencephalic injection in rats was 219 mg I/kg for DL-3-117, 61.9 mg I/kg for metrizamide, and 154.1 mg I/kg for iopamidol, which are significantly different. A dose of 300 mg I/kg injected into a permanently cannulated lateral ventricle produced neurofunctional deficits with all contrast media except DL-3-117, which scored equal to Ringer's solution. Metrizamide and iopamidol in the same model, adapted for aversion conditioning, induced aversion with 45 mg I/kg, while DL-3-117 did not condition the rats.

Animals↗

Prebiotic peptide-formation in the solid state. I. Reactions of benzoate ion and glycine with adenosine 5'-phosphorimidazolide.

The reactions of benzoate ion and of glycine with adenosine 5-phosphorimidazolide have been investigated. Benzoate reacts first to give the anhydride, benzoyl-adenylate, which, in the presence of excess imidazole, reacts further to give the 2'- and 3'-esters of adenosine 5'-phosphate. Glycine also first attacks the imidazolide to give an anhydride, but this compound may react further either to give 2- and 3'-esters or to form peptides, depending on the reaction conditions.

Adenine Nucleotides↗

Spectral analysis of Lapine EEG: neurotoxicologic evaluation of new nonionic contrast media.

Effects of the injection of 0.25 ml of nonionic radiocontrast media (280 mg I/ml) and/or istonic and/or hypertonic mannitol into the subarachnoid space on the low frequencies (2--5 Hz) of the EEG were studied in nonanesthetized, curarized rabbits. Compared to the noninjected controls, mannitol did not cause any significant EEG spectrum shifts. P-297 and iopamidol caused a slight decrease in the energy content of the 2--5-Hz band, while DS-1-132 and the nonionic dimer ZK 32347 caused a moderate increase. Since an increase in the slow-wave component of the EEG indicates a pacemaking activity, while a decrease indicates stimulation or irritation, none of the tested nonionic media appear to be biological inert. In this test P-297, iopamidol, and DS-1-132 caused fewer disturbances than metrizamide.

Animals↗

Combined methods for assessment of neurotoxicity: testing of new nonionic radiographic media.

A battery of tests for toxicity assessment of new contrast media is reviewed. Cell toxicity in a protozoan culture (Blepharisma americanum); lethal dose determination in mice; EEG Spectral analysis following cisternography in rabbits; ED50 and LD50 determination by intra- and pericerebral injection in rats; intracisternal injection in chronically cannulated, nonanesthetized rats; and aversive conditioning by intracisternal injection in rats were found complementary. By these methods, novel nonionic media phenyl-sugar-ether DS-1-132 and DL-2-99 were found comparable to iopamidol, while all three compounds were superior to metrizamide.

Animals↗

Syntheses of new nonionic radiographic contrast media: acylamino-triiodophenyl ethers of sugars.

New, potentially useful radiographic contrast media, employing hexoses attached to the triiodophenyl moiety by an ether bond, have been synthesized and tested. Two of the nitro groups in trinitrobenzene were displaced by two fully protected glycose-3-yl residues. The bis-ethers (IV) were successively reduced, iodinated, acylated, and then subjected to base and/or acid catalyzed deprotection to obtain the acylamino-triiodophenyl ethers (VIII). The bis-glucose-3-yl ether (VIIIa) was converted into the corresponding bis-arabinos-2-yl ether (XIII) by standard methods. These sugar ethers have high water solubility, hydrolytic stability, and low toxicity. The glycolyl-bis-hexose ether DL-2-98, which has the lowest neurotoxicity in this series of compounds, is comparable to iopamidol, and is potentially useful as a new nonionic radiographic contrast agent.

Animals↗

Stability of nonionic water-soluble contrast media: implications for their design.

The stability of the nonionic contrast media metrizamide, P-297, iopamidol, and nonionic phenyl ether DS-1-132 was studied by exposing their aqueous solutions to 120 C. Metrizamide showed decomposition of the sugar residue, while in P-297 the sugar substituent was cleaved off the triiodoaniline moiety. Iopamidol and DS-1-132 showed no decomposition. For stability, sugar moieties should be attached either by an ether linkage or as amides, as long as the acylamino group is not on a carbon adjacent to the anomeric carbon. Polyhydroxyalkylamines are less hydrophilic but more stable than sugars.

Chemical Phenomena↗

Determination of lethal dose in a protozoa: screening of contrast media toxicity.

Suitability of a protozoan culture for determination of contrast media (CM) toxicity was investigated. A culture of Blepharisma americanum was exposed to varying concentrations of CM and the time elapsed until 50% cell mortality was determined. The cultures were standardized using solutions of Na iothalamate and/or Metrizamide. A standardized culture responded reproducibly between days 6 and 10 of the culture age. Comparison of concentrations of CM needed to achieve LD50 at 7 minutes ranked CM in order of decreasing toxicity as follows: oral cholecystopaques, intravenous cholecystopaques, and urographic agents; ie ionic monomers, ionic dimers, monovalent dimers, nonionic monomers, nonionic dimers. Comparison of CM toxicity determined by protozoa LD50 at 7 minutes with i.v. LD50 in mice showed a good correlation, suggesting usefulness of the protozoan assay as a complementary or screening toxicologic method.

Contrast Media↗

Development and preliminary pharmacologic evaluation of a zwitterionic oral cholecystographic agent.

A new zwitterionic iodinated molecule, 2-[3-(N-ethyl-2-hydroxyethyl) amino-acetamido-2, 4, 6-triiodobenzyl]-butyric acid (RCK-136) was synthesized, and its potential as an oral cholecystopaque was tested. In rats, 15 minutes following intravenous injection, RCK-136 reached maximum biliary concentration; 84% of the dose was excreted into bile. Biliary excretion of RCK-136 elicited a strong choleresis (44 ml of bile flow per mmol compound). Intravenous LD50 in rats averaged 390 mgI/kg. ED50 in rats, intradiencephalic, averaged 1.98 mgI/kg. The average densities of cholecystograms produced in three dogs with iosumetic acid and/or RCK-136 were comparable.

Animals↗

Evaluation of intrathecal contrast media by aversion conditioning in rats.

A method for quantification of aversion conditioning in rats was adapted to assess intrathecal neurotoxicity of contrast media (CM). Metrizamide, iopamidol, nonionic dimers DL-2-87 and DL-3-117, experimental iodophenyl glucose ethers DL-2-98 and DS-1-132, and Ringer's solution were injected into non-anesthetized rats drank water mixed with their preferred flavors, and subsequently were injected with 22.5 and/or 45 mgI/kg (200 and/or 400 mgI/ml concentration). From the intake of the preferred flavored water, expressed as percentage of total fluid intake consumed during a preference test and during a subsequent free choice test, a percentage avoidance/preference score was calculated as a measure of conditioning. At 12.5 mgI/Kg level, DL-2-87, which unexpectedly precipitated from solution in vivo, caused the most aversion, followed by metrizamide. The remaining compounds induced no significant aversion and were statistically indistinguishable from one another. At 45 mgI/kg dose level, all monomeric CM induced aversion of a statistically equal degree, while DL-3-117 proved nonaversive, equal to Ringer's solution.

Animals↗

Iotrol, a new myelographic agent: 2. Comparative electroencephalographic evaluation by spectrum analysis.

Iotrol, a nonionic dimer isotonic with cerebrospinal fluid at 300 mg l/ml, was evaluated against metrizamide, iopamidol, and iohexol by electroencephalography (EEG) in nonanesthetized cynomolgus monkeys. Each of four monkeys was injected intrathecally with 0.5 ml/kg of 300 mg l/ml of each contrast medium. EEG was obtained before, 45 min, and 3 hr postinjection. EEG spikes, motor disturbances, convulsions, and behavior changes were observed. The EEG from C3 channel was also computer-analyzed. Average percentage differences between control and test energy content of the entire EEG and of the EEG spectrum subdivided into five frequency bands were calculated. With metrizamide, three animals suffered seizures, and all were lethargic and irritable. With iopamidol, two animals convulsed; all animals were lethargic. Transient apathy and motor disturbances were observed in the iohexol animals. No motor or behavior changes were produced by iotrol. Metrizamide and iopamidol increased the spectrum energy in all bands. Neither iohexol nor iotrol affected the EEG significantly. On the basis of these findings, iotrol holds promise as a clinical contrast material for the subarachnoid space.

Animals↗