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Iopamidol and ioxaglate are two new contrast media which have an osmolality approximately half that of diatrizoate for the same iodine concentration. These three contrast media were compared with each other and with Hartmann's solution during coronary arteriography in dogs using hemodynamic and electrocardiographic parameters in addition to coronary venous sinus sampling to measure changes in osmolality, electrolyte, and contrast media concentration. Iopamidol and ioxaglate had similar, but less toxic, effects in comparison with diatrizoate. These new contrast media may offer a reduction in the morbidity and mortality of coronary arteriography.

Shoot organogenesis occurs when leaf explants of Convolvulus arvensis are cultured on Murashige and Skoog salts, sucrose, vitamins, and 0.05 mg/liter IAA with 7.0 mg/liter 2-isopentenyl adenine. Under the influence of this shoot inducing medium (SIM), the explants become competent for the organogenic effects of SIM and eventually become determined for shoot formation. The induction process includes five separate transient sensitivities to inhibitors. Such stage-specific inhibitions reflect phenocritical times in development rather than general metabolic toxicities. The phenocopying agents are tri-iodobenzoic acid (TIBA), sorbitol, ribose, ammonium ion, and acetylsalicylic acid. The process of in vitro shoot organogenesis from leaf explants is now seen to include a series of discrete steps which precede morphological differentiation. An initial dedifferentiation process results in the formation of competent callus tissue along the cut edges of the explant. Under the influence of the phytohormone balance in SIM, shoot organogenic induction proceeds. This process involves a time which is sensitive to inhibition by salicylates followed by a time sensitive to TIBA which is followed in turn by a time sensitive to sorbitol and culminates in cells or groups of cells determined for shoot formation. This process also includes a time sensitive to inhibition by ribose, although its place in the order of events is not yet firmly assigned. There is also a sensitivity to ammonium ion (or lack of nitrate) at or near the time the explant becomes determined for shoot production.

In 10 patients coronary sinus blood flow (CSBF) was measured during and after injection of iohexol and meglumine-Na-Ca metrizoate in the left coronary artery. Oxygen saturation, lactate concentration and hematocrit were determined in the aorta and coronary sinus before and after a second injection of the two contrast media. The increase in CSBF was significantly more marked and sustained after injection of metrizoate than after iohexol and myocardial arterio-venous oxygen difference was significantly lower. Myocardial oxygen consumption and lactate metabolism were not adversely affected by any of the contrast media. The fall in hematocrit in coronary sinus blood was significantly greater after metrizoate.

Pulmonary inactivation of prostaglandin E2 (PGE2) was investigated in isolated perfused rat lungs during infusion of ionic and nonionic radiographic contrast media (RCM). When 100 nmol of [14C]-PGE2 was infused slowly into the pulmonary circulation, the ionic ioglycamate decreased the metabolism of PGE2, but other ionic (diatrizoate and ioxaglate) and nonionic RCM (iopamidol and metrizamide) had no significant effect. When a smaller amount of [14C]-PGE2 (10 nmol) was injected as a bolus the metabolism of PGE2 was decreased also by diatrizoate and ioxaglate, but not by iopamidol. After a similar bolus injection of 10 nmol of [14C]-PGE2, the efflux of radioactivity from the lungs was increased by diatrizoate, ioglycamate and ioxaglate but remained unchanged by iopamidol and metrizamide. The RCM infusion did not change the perfusion pressure. The present study indicates that ionic RCM decrease the inactivation of PGE2 in rat lungs and thus possibly increase the circulating level of this prostaglandin.

Iotrolan, a nonionic, hexaiodinated dimer, is an extremely hydrophilic compound (P = 0.005). Due to its larger Stokes' radius compared with monomeric compounds such as metrizamide, the diffusion time through membranes is extended. Iotrolan deforms erythrocytes only minimally. There is practically no binding to plasma proteins. The new contrast agent has been shown to exert a very limited effect on the complement system (in vitro); it does not inhibit lysozyme (a standard enzyme) in concentrations less than 100 mg I/ml. To inhibit activity of the enzyme collagenase, much higher concentrations of iotrolan than of metrizamide or iopamidol are needed and this could offer an advantage when used for diskography preceding diskolysis with collagenase. After a single intravenous injection in rats, iotrolan has an LD50 of 28.3 g I/kg - the best general tolerance known for water-soluble contrast media thus far. The superior tolerance of iotrolan compared with iohexol and iopamidol (p less than or equal to 0.05) in rats is statistically significant. On the basis of preclinical experience, iotrolan is a very promising contrast medium for intrathecal and intravascular use.

Injury to the aortic endothelium in rats was evaluated under a light microscope by a silver staining method after application of ionic monomeric (diatrizoate and metrizoate), non-ionic monomeric (C29 with different pH and buffers, 593, iohexol and metrizamide) and monoacidic dimeric (ioxaglate) contrast media, and iso- and hypertonic solutions of sodium chloride. In iodine equivalent concentrations the ionic monomers were significantly more toxic than the other contrast media. No significant was found between the non-ionic monomers, monoacidic dimer and sodium chloride solutions equiosmolal to the ionic monomers. Isotonic saline was the least harmful solution.

The central and renal haemodynamic effects after intravenous infusion (1 ml/s) of a non-ionic (iohexol) and an ionic (metrizoate) contrast medium were investigated in 16 pigs. The injected contrast media induced marked haemodynamic changes compared with normal saline. However, there were no significant differences between the ionic and the non-ionic media. It was concluded that the effects were only partially caused by an increase in the blood volume due to the injected volume. In addition, the effects related to the viscosity, the osmolality and other not specified pharmacodynamic properties of the media are proposed to be of importance.

3,4,5-Triiodobenzoic acid, known as auxin transport inhibitor, stimulates specific [3H]verapamil binding to zucchini microsomes by 100% (EC50 = 1 microM). This stimulatory effect is due to a decrease of the apparent equilibrium dissociation constant KD for verapamil from 60 nM to 33 nM without significantly changing the maximum number of binding sites. 3,4,5-Triiodobenzoic acid also increases specific [3H]verapamil binding to rabbit skeletal muscle membranes (EC50 greater than or equal to 20 microM) without affecting [3H]nitrendipine and [3H]-d-cis-diltiazem binding. If 3,4,5-triiodobenzoic acid is added to isolated rings of rabbit A. saphena contracted by potassium depolarization, a dose-dependent relaxation is observed with an IC50 value of about 8 microM. Contractions initiated by the addition of 3 microM norepinephrine can also be abolished by 3,4,5-triiodobenzoic acid with half maximal inhibition at 40 microM.

The aim of this study was to establish the effects of two iodine-containing radiological contrast media (ioxaglate and diatrizoate) on plasma iodide, thyroid hormones and TSH in a group of 20 subjects (8 females, 12 males). The following were evaluated two, eight and 30 days after administration of the drugs: plasma iodide, T4, T3, rT3, FT41, TSH before and after TRH (250 micrograms IV). 131I uptake was measured before the media were given and 30 days afterwards. The results were compared at the different times during the investigation using Wilcoxon's signed ranking test for non-parametric variables. Plasma iodide was found to be above the normal range two to eight days after ioxaglate and two to eight and 30 days after diatrizoate. After ioxaglate, rT3 was increased at eight days and T3 at 30 days. 131I uptake remained low after the 30th day. After diatrizoate, T4 was decreased on the second day and FT41 was low, on the eighth and 30th day. All figures represent statistically significant but nevertheless minor variations of the initial value of each parameter. In conclusion, although ioxaglate and diatrizoate lead to variations in plasma thyroid hormone levels, they are of little importance.

An in vitro and in vivo study of the effect of ionic and nonionic contrast media (CM) on coagulation and platelet function is reported. The methods employed were tests for extrinsic and intrinsic coagulation together with a fibrinolytic parameter and aggregation using ADP and collagen as inducers. The in vivo study utilized patients undergoing routine cerebral angiography. The in vitro results showed a modest influence of the nonionic CM in contrast to the ionic. The marked inhibitory effect of the latter was mainly caused by inherent toxicity, osmolality/ionic strength being of minor importance. The in vivo results showed a negligible influence of CM on systemic hemostatic parameters, but catheter-derived samples indicated desirability of premedication with ASA or heparin. The nonionic CM caused less discomfort than the ionic CM.

The haemodynamic and cardiac side effects of the new non-ionic contrast medium, iohexol, were investigated anaesthetized rats and isolated perfused rabbit hearts. Iohexol, caused a positive inotropic response in both models, elevated coronary flow and in high doses had an inhibitory influence on the cardiac conducting system. From a comparison with Amipaque and Urografin 76 it was concluded that with respect to cardiac side effects iohexol can be ranked between these media.

Selective visceral angiography was performed with the ionic, monoacidic, dimeric contrast medium ioxaglate (280 and 320 mg I/ml). Twenty patients with and without disease of the liver and/or pancreas were prospectively and consecutively studied. Changes in the serum activities of ALAT, ASAT, GT, AP, and pancreatic isoamylase and changes in the level of serum bilirubin, prothrombin index and haematocrit were evaluated sequentially before and after angiography. The total volume of contrast medium ranged from 100 to 340 ml per patient and the median dosage was 3.5 ml per kg body weight. There was no statistically significant elevation within the entire group of patients in the measured parameters after angiography when compared with pre-angiographic values. No clinically important toxic effect on the liver or pancreas induced by the contrast medium was found.

The pharmacokinetic behaviour of intravascular renal and biliary contrast agents is being evaluated with help of CT-densitometry. Contrast enhancement is best with high-dose bolus injection and rapid sequence CT-scanning of at least 4 cuts per minute.

The effects of the first injections in humans of iopentol, a new non-ionic contrast medium, are briefly reported. Detailed descriptions will be published elsewhere. Iopentol was well tolerated when injected intravenously into 24 healthy male volunteers in doses of 300 to 1,200 mg I/kg body weight and was excreted almost entirely in the urine in unchanged form. The results indicate that iopentol may be used in clinical trials in patients.

In a previous in vitro study we demonstrated reduced CO2 production in rat hippocampal tissue when metrizamide was added. This metabolic depression is believed to be a result of the 2-deoxy-D-glucose (2-DG) portion of the metrizamide molecule since 2-DG is a known competitive inhibitor of glucose metabolism. This competitive inhibition probably occurs at the cell membrane since it has never been shown that metrizamide penetrates neural cells. Further the inhibition is most likely related to competition for the membrane glucose carrier. A new nonionic contrast medium, iohexol, does not contain a 2-DG component and if the hypothesis for the metabolic inhibition is valid we should not expect metabolic inhibition with iohexol. This hypothesis was tested using the rat hippocampus model previously used for metrizamide. We compared iohexol with metrizamide in isotonic concentrations and also examined the effect of hypertonicity. These experiments did not demonstrate inhibition of CO2 production with iohexol at near physiologic osmolalities, however, there was a marked depressive effect with increasing osmolality. This effect from hypertonicity is, however, probably of less importance in vivo where water will rapidly diffuse toward the hypertonic areas. The apparent lack of interference of the iohexol molecule on glucose metabolism should therefore make iohexol a more suitable contrast medium, for subarachnoid investigations than metrizamide.

Low-osmolar intravascular radiographic contrast media have recently been introduced for clinical use in an attempt to reduce the frequency and severity of side effects. This study was undertaken to test patients' subjective reactions to IV injection of three different types of contrast media--iopamidol, meglumine/sodium ioxaglate, and sodium iothalamate. The low-osmolar contrast media (ioxaglate, iopamidol) were found to have a significantly lower frequency of nonidiosyncratic reactions than the high-osmolar contrast media (iothalamate). However, in view of the present cost of low-osmolar contrast media and the relatively minor nature of nonidiosyncratic reactions, it is concluded that high-osmolar contrast media should remain the contrast media of choice for routine IV use.

The effect of thyroid function was investigated in 22 patients undergoing arteriography with a new low osmolality contrast medium--sodium and meglumine ioxaglate (Hexabrix). Plasma thyroxine (T4), thyroxine resin uptake (TRU) and free thyroxine index (FTI) were measured before and at varying intervals up to 56 days after the arteriogram. Despite the large doses of Hexabrix used (up to 89.6 g of iodine), these tests of thyroid function did not reveal any significant change from pre-angiographic levels. It is concluded that Hexabrix as used for arteriography does not affect thyroid function.

The renal blood flow as examined in six dogs for 2 h after contrast agent injection into the renal artery using the dye dilution method. After injection of an ionic contrast agent (iodamide) there was an initial vasodilatation and later constriction, but the blood flow was back to normal after 10-15 min. Ioxaglate caused a similar initial response, but after a relatively large dose the blood flow remained below normal for 2 h. Metrizamide caused an immediate reduction in the blood flow, which remained constantly reduced for 2 h. A total cessation of the renal blood flow was seen in two cases.

Nonionic contrast media represent a significant advance for myelography due to their substantially lower neurotoxicity. Some side effects have been noted with metrizamide, however. Origins of adverse effects have not been clearly defined. Studies reviewed here investigated the effects of two nonionic contrast media, metrizamide and iohexol, on glucose metabolism in neural tissue cells in vitro using rat hippocampal tissue slices. Isotonic metrizamide produced metabolic disturbances that may partially explain some clinical adverse effects. It was hypothesized that iohexol, which, unlike metrizamide, does not contain a 2-deoxy-D-glucose component, would not have this effect. A series of in vitro experiments compared the two media. Results showed no evidence that iohexol caused metabolic disturbances, but in vitro there was a depressive effect on metabolism from hypertonicity. In vivo water will rapidly diffuse toward hypertonic areas, thus neutralizing the osmotic effect. The lesser metabolic effect suggests that iohexol would be safer than metrizamide for subarachnoid examinations.

The effects of intracoronary injection of two nonionic contrast media (iohexol and metrizamide) on myocardial contraction and chemical composition of coronary sinus (CS) blood were compared with those caused by the standard ionic contrast material for coronary angiography, sodium meglumine diatrizoate (R76), in 14 anesthetized dogs. The effects of each agent on regional contractility were compared in the normal state and in the presence of a critical coronary artery stenosis. The three contrast media produced equivalent decreases in hematocrit and sodium (both NS), but R76 caused a greater increase in CS osmolality (p less than 0.02). R76 caused a significant decrease in CS potassium and ionized calcium (both p less than 0.001), but neither nonionic contrast medium caused a significant change in either potassium or calcium. In the normal state, R76 caused initial transient (less than 10 seconds) increases in both end-diastolic (p less than 0.006) and end-systolic segment length (p less than 0.02) and a decrease in rate of change of segment length (dL/dt) (p less than 0.002). The nonionic agents caused a mild increase in dL/dt (p less than 0.04) and a decrease in end-systolic segment length (p less than 0.03); both returned to control levels within 1 minute. In the presence of a stenosis, R76 caused a more severe and prolonged increase in end-diastolic and end-systolic segment lengths (p less than 0.03) and a decrease in dL/dt (p less than 0.002), which did not return to control within 2 minutes. The effects of the nonionic agents were similar in both normal and diseased states. We conclude that nonionic contrast media produce fewer alterations than ionic contrast media in coronary sinus blood chemistry and myocardial contractile state. The effect of ionic contrast media on regional contraction is accentuated in the presence of coronary artery stenosis.

The intravascular contrast media in current use are solutions of salts of tri-iodinated substituted benzoic acids. Haemodynamic changes following injection of these contrast media are due mainly to their high osmolar concentration which is five to eight times physiological levels. In this study we compare the effect in dogs on femoral arterial flow following femoral arterial injection of three new low osmolality contrast media (Amipaque, Iopamidol and Hexabrix) compared to conventional contrast media (Coronary 280). Conventional salts such as Conray 280 cause a marked vasodilatation and increase in femoral blood flow to about twice pre-injection levels. The three new low osmolality contrast media cause much less vasodilation and increase in femoral blood flow (+32%). There was no significant difference between the effects of any of the three new media. The experiment suggests that any of three new low osmolality contrast media should be suitable for femoral arteriography as they cause much less vasodilatation (and therefore discomfort) than conventional contrast media. Our results do not indicate a preference for any of the three new contrast agents.

The effect of phenobarbital pretreatment (PB; 75 mg/kg i.p. once daily for 5 days) and the simultaneous administration of taurocholate (TC; 200 mumol/kg i.v.), eosin(EO; 40-160 mumol/kg i.v.) and iodoxamic acid (IA; 125--500 mumol/kg i.v.) on the hepatic uptake and biliary excretion of BSP (30--120 mumol/kg i.v.) and BSP--GSH (40--160 mumol/kg i.v.) was investigated on diethyl maleate (DEM)-pretreated rats. The biliary excretion of BSP was not influenced by PB and EO, while it was increased by TC and decreased by IA. In contrast, the excretion of BSP--GSH was not influenced by TC or IA, it was stimulated by PB and inhibited by EO. In the different experimental conditions the hepatic uptake of BSP and BSP--GSH changed similarly: PB did not influence, TC, EO and IA decreased the accumulation of BSP and BSP--GSH in the liver. These results indicate that qualitative differences exist in the hepatobiliary transport of BSP and BSP--GSH, which manifest themselves following their hepatic uptake.

The femoral blood flow was measured before, during and three min after random injection of iodixanol, iopentol, iohexol and metrizoate into the femoral arteries of 12 beagle dogs. The doses were 0.15 and 0.30 ml/kg body weight. Concentrations were 320 mg I/ml. The maximal increases in blood flow were (median values are presented and the lower dose is given first): iodixanol 9% and 32%, iopentol 28% and 66%, iohexol 43% and 77%, and metrizoate 161% and 215%. At both doses iodixanol produced significantly smaller flow increase than any other medium. At both doses iopentol and iohexol produced significantly smaller flow increase than metrizoate (p less than 0.005). There was no significant difference between iopentol and iohexol (p greater than 0.1).

In 28 cardioangiographies and 24 peripheral angiographies the dimer ioxaglate (Hexabrix) and conventional monomeric contrast media were compared. The general effects of the media on the patients were the same, while the frequencies of pain, sensations of heat and involuntary movements were significantly lower with Hexabrix.

Some characteristics of the gravity sensing mechanism in maize root caps were investigated using a bioelectric current as an indicator of gravity sensing. This technique involves the measurement of a change in the current density which arises at the columella region coincidently with the presentation time. Two inhibitors of auxin transport, triiodobenzoic acid and naphthylphthalamic acid, blocked gravitropic curvature but not the change in current density. Two inhibitors of calmodulin activity, compound 48/80 and calmidazolium, blocked both curvature and gravity-induced current. The results suggest that auxin transport is not a component of gravity sensing in the root cap. By contrast, the results suggest that calmodulin plays an intrinsic role in gravity sensing.

Forty anaesthetized rabbits were injected subarachnoidally with equimolal doses, 0.48 mmol/kg body weight (= 185 mg I/kg), of iohexol and metrizamide, administered in solutions iso- and hyperosmolal to the CSF. Concentrations of Na, K, Ca and Mg in the CSF were determined before and 3 hours after the contrast medium injections. Iso-osmolal iohexol caused a uniform decrease in all four cations, which was believed to be a simple dilution. The hyperosmolal solution of iohexol caused a significant relative increase in Ca compared with Na, K and Mg. Both metrizamide solutions caused an increase in Ca over its pre-injection level and a significant relative increase of both Ca and Mg as compared with Na and K. The changes caused by the three latter solutions were consistent with an increase in the blood-brain barrier permeability.

The authors studied the effect of the non-ionic radiopaque substance Omnipaque-350 on the central hemodynamics and myocardial contractility. A comprehensive angiographic examination was conducted in 25 patients. Omnipaque-350, when administered intravascularly, was found to induce the same general reactions as ionic triiod-containing radiopaque. It did not exert direct myocardiodepressive effect; yet, upon intracoronary administration it caused uniform changes in myocardial contractility and elasticity which corresponded to transitory alterations in its perfusion. During left ventriculography, Omnipaque-350 as compared with Urografin-76, has less marked hypervolemic properties and a less significant impact on the central hemodynamics and the pump function of the heart.

A test was carried out on 11 young, full sized mongrels to determine whether there is an interaction between chymopapain and the contrast agents iotrolan and iopamidol. A total of 75 intervertebral disks were punctured: nucleolysis alone was performed on 20, diskography with iotrolan and subsequent nucleolysis on 20, and diskography with iopamidol and subsequent nucleolysis on 10. Diskography alone was performed 10 times with iotrolan and 5 times with iopamidol. Aqua dest. was given intradiskally 5 times, and puncture was carried out 5 times without the administration of any substance. Following puncture, x-rays of the lumbar vertebral column were taken laterally: daily for the first 10 days, then weekly. Disk space narrowing typical of nucleolysis with chymopapain was found among the disks that were nucleolyzed only to the same extent as among those that had undergone diskography previously. There was no evidence of narrowing of the other disk spaces which had been punctured but not treated with chymopapain. On some of the dogs, CT and MRI examinations were carried out. The CTs showed a homogenous hypodensity in all of the disks, in which chymopapain had been injected. The MRI revealed a signal loss in all of the nucleolyzed disks. The results of short and long term follow up demonstrate that inhibition of chymopapain by iotrolan or iopamidol is not to be expected and therefore diskography prior to chemonucleolysis can be performed without danger of enzyme inactivation.

We studied the hemodynamic and electrocardiographic responses to left ventriculography and coronary arteriography with three angiographic contrast agents. Two were nonionic agents (ioversol 32% iodine, 60 patients, and iopamidol 37% iodine, 30 patients). The third was a conventional ionic agent (diatrizoate 37% iodine, 30 patients). Cardiovascular hemodynamics and the electrocardiogram were recorded for 5 minutes after left ventricular injection and for 2 minutes after coronary injections. Following left ventriculography, diatrizoate caused a greater increase in cardiac output, left ventricular end diastolic pressure, and corrected QT interval while causing a greater decrease in arterial pressure than did either ioversol or iopamidol, which were indistinguishable from each other. Following left coronary arteriography, diatrizoate caused a significant decrease in heart rate, prolongation of the corrected QT interval, and increase in T wave amplitude. In contrast, neither ioversol nor iopamidol caused significant changes in any electrocardiographic parameters. Adverse reactions were more common with diatrizoate than with either ioversol or iopamidol. There were no recognizable differences in angiographic image quality among the three agents. We conclude that the angiographic performance of ioversol is equivalent to that of iopamidol and that both cause less hemodynamic and electrocardiographic disturbance than diatrizoate.

The authors previously showed that metrizamide causes an inhibition in CO2 production in rat neural tissue. The purposes of this work were to test if this inhibition was the result of a competitive inhibition of metrizamide with the D-glucose transport system and to test the effect of other contrast media. Deoxyglucose was used as a marker for glucose. The first cellular system using rat hippocampus slices was designed to examine the effect of 15 mM and 80 mM metrizamide on deoxyglucose uptake. The second cell-free system, using isolated rat brain synaptosomes, was designed to evaluate more accurately the mechanism and kinetics of metrizamide's inhibitory effect on the uptake of deoxyglucose and to compare metrizamide to other nonionic contrast media (iohexol, iopamidol, iotrol, and iodixanol). These experiments demonstrate that there is inhibition of D-glucose uptake only in hippocampus slices and that the inhibition is dependent on the concentration of metrizamide. This does not, however, appear to be a competitive inhibitory effect on the carrier such as that between D-glucose and 2-deoxy-D-glucose. In synaptosomes, none of the contrast media had a significant effect on the uptake of 2-deoxyglucose.

Ioversol 320, a new nonionic iodinated contrast medium, was injected intravenously into 24 healthy male volunteers using saline as a control. Physical examination, vital signs, electrocardiogram, biochemical and hematological data were recorded before and at intervals after injection. No significant changes were observed. Seventeen volunteers reported no side effects; six volunteers had mild transitory symptoms considered to be related to the contrast medium. The authors conclude that broader clinical trials can be safely conducted to determine safety and tolerability of ioversol.

The hyperosmolality of current ionic angiographic media gives rise to several adverse effects. Use of the first low-osmolality medium, metrizamide (Amipaque), has been inhibited by expense and by the necessity for prior mixing into solution. Hexabrix is the first of such media to be available in stable solution, and its use in angiocardiography is reported, in direct comparison with Urografin, Triosil, Cardio-Conray, and metrizamide. The low osmolality media cause significantly less discomfort than ionic media, and are better tolerated in paediatric angiocardiography. In coronary angiography Hexabrix causes comparable T wave change to Urografin and more than Triosil or metrizamide, but tends to have less effect on heart rate. The risk of exacerbating pulmonary arterial hypertension in right heart angiography appears to be reduced.

The effects of various exogenous auxins and polar auxin transport inhibitors on somatic embryogenesis in carrot cultures were investigated. Indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid do not disrupt the sequence or the polarity of individual stages in embryo development, but tend to cause developing embryos to revert to undifferentiated callus, with increasing frequency in later embryo stages. The transport inhibitors, N-(1-naphthyl)phthalamic acid and 2,3,5-triiodobenzoic acid, block morphological transitions to the subsequent stage; for example, they cause the formation of enlarged globular and oblong embryos. Heart embryos in these treatments usually develop additional lateral growth axes. These results shed light on the role of auxin and its polar transport in somatic embryogenesis.

Trypan blue and 197HgCl2 were used as markers of the increased leakage through the blood-brain barrier which developed after selective injection of different contrast media formulations into the internal carotid arteries of rabbits. Interest was focused on a new, experimental, nonionic medium (C-29) and possible effects resulting from the addition of Ca2+ and Mg2+ to nonionic contrast media. Using 197Hg, it was possible to quantitate the increase in extravasation produced by the contrast media. C-29 caused less damage than either metrizamide or meglumine iothalamate. The addition of Ca2+ and Mg2+ to nonionic contrast media seemed to stabilize the blood-brain barrier.

The tomato (Lycopersicon esculentum, Mill.) mutant diageotropica (dgt) exhibits biochemical, physiological, and morphological abnormalities that suggest the mutation may have affected a primary site of auxin perception or action. We have compared two aspects of the auxin physiology of dgt and wild-type (VFN8) seedlings: auxin transport and cellular growth parameters. The rates of basipetal indole-3-acetic acid (IAA) polar transport are identical in hypocotyl sections of the two genotypes, but dgt sections have a slightly greater capacity for IAA transport. 2,3,5-Triiodobenzoic acid and ethylene reduce transport in both mutant and wild-type sections. The kinetics of auxin uptake into VFN8 and dgt sections are nearly identical. These results make it unlikely that an altered IAA efflux carrier or IAA uptake symport are responsible for the pleiotropic effects resulting from the dgt mutation. The lack of auxin-induced cell elongation in dgt plants is not due to insufficient turgor, as the osmotic potential of dgt cell sap is less (more negative) than that of VFN8. An auxin-induced increase in wall extensibility, as measured by the Instron technique, only occurs in the VFN8 plants. These data suggest dgt hypocotyls suffer a defect in the sequence of events culminating in auxin-induced cell wall loosening.

Over the last two or three years, a considerable and almost universally favorable experience has been obtained in Europe with the low osmolality contrast agents. These agents, such as Hexabrix, iohexol and iopamidol have been shown to reduce the subjective pain and heat sensation associated with hyperosmolar agents. Hexabrix, although an ionic agent, has achieved a slightly greater reduction in osmolality than other low osmolality contrast agents. Low osmolality media have shown reduced chemotoxic effect on red cells, less histamine release, fewer electrocardiographic changes, and less marked hemodynamic changes compared with conventional agents. The new contrast media may be predictably safer, especially for high risk patients.

Monocytes were separated from human blood with Nycodenz, an iodinated gradient medium. Monocytes have a lower average density than lymphocytes, but because of overlapping efficient separation cannot be achieved on the basis of density differences alone. Thus the isolation procedure was based on the assumption that the low-density fraction of lymphocytes increases its density more than monocytes by expelling water when exposed to an increased osmolarity. Thereby they might pass through a density barrier present initially, whereas the monocytes remain at the top of the gradient layer. Separation fluids with densities ranging from 1.061 to 1.096 g/ml were prepared by mixing Nycodenz with NaCl solutions of various concentrations. EDTA-blood (3 ml) or a leucocyte suspension (2-6 ml) obtained by dextran sedimentation was loaded on 3 ml of separation fluid and centrifuged for 15 min at 1900 rpm. Then the cells in the interface region were collected. At each density level it was possible to obtain an almost pure monocyte suspension (95-98%) by increasing the osmolarity. However, the higher the purity, the lower the monocyte yield. Apparently, the viability of monocytes was not affected, even when subjected to an osmolarity of 600 mosmol. For routine use, it appears that separation fluids with densities from 1.061 to 1.078 g/ml and corresponding osmolarity in the 300 to 410 mosmol range are suitable.

The new low-osmolar contrast agent ioversol was compared with the conventional ionic contrast agent diatrizoate in 60 patients undergoing routine abdominal (21 patients) and peripheral (39 patients) arteriography. The effects on hemodynamics, various laboratory parameters, and patient comfort were evaluated. In peripheral arteriography, there was less discomfort with ioversol as well as decreased magnitude and incidence of hypotension (P less than .001) after injection. In visceral arteriography, there was no significant difference between the two agents. Overall, the incidence of ECG changes was small in both groups (ioversol 2%, diatrizoate 8%). The two media were equivalent in incidence of adverse reactions (eg, nausea, vomiting, urticaria), the effect on laboratory parameters, and in the diagnostic adequacy of the radiographs. We conclude that ioversol is safe and efficacious for peripheral and visceral arteriography. In peripheral arteriography it causes less patient discomfort and, perhaps more importantly, fewer hemodynamic alterations than diatrizoate. These differences in hemodynamic effects may be important in patients with hemodynamic instability or limited cardiovascular reserve.

The effects of contrast media on left ventricular (LV) relaxation as assessed by the time constant of isovolumic relaxation have not previously been studied. A new nonionic contrast agent (iohexol) has been shown to have fewer deleterious effects than standard ionic agents. Nineteen patients received iohexol and sodium meglumine diatrizoate (Renografin-76) in a double-blind, crossover study during left and right coronary arteriography and with simultaneous high-fidelity micromanometer measurements of LV pressure. Neither agent induced significant changes in LV end-diastolic pressure after right or left coronary arteriography. After right coronary arteriography, neither agent produced significant deterioration of peak positive dP/dt or (dP/dt)/DP40 (dP/dt at a developed pressure of 40 mm Hg). However, after right coronary arteriography both agents caused a transient deterioration in peak negative dP/dt and the time constant of isovolumic relaxation (p less than 0.05 at 20 seconds after arteriography). After left coronary arteriography, sodium meglumine diatrizoate induced deterioration of systemic blood pressure (p less than 0.05), peak positive dP/dt (p less than 0.01), (dP/dt)/DP40 (p less than 0.05), peak negative dP/dt (p less than 0.01) and the relaxation time constant (p less than 0.01). These effects were not induced by iohexol. Thus, nonionic contrast media exert negligible alterations on LV function when used for coronary arteriography. The findings are of potential clinical importance in view of the large number of patients with depressed LV function who undergo coronary arteriography.

Intravenous administration of radiographic contrast media (CM) significantly decreases cerebrospinal fluid (CSF) production as measured by negative pressure collection from a lateral ventricle of the anesthetized dog. This effect has been shown with the conventional ionic CM, sodium diatrizoate, and is now reported for the new nonionic agent, iohexol. Continuous infusion of either agent maintains the decrease. The magnitude of the CM-induced decreased CSF production is proportional to the dose in the range of 1 to 4 ml/kg. This action of CM cannot be explained by an osmotic mechanism. Two enzymes involved in the elaboration of CSF, carbonic anhydrase and sodium, potassium-adenosine triphosphatase, are not inhibited by sodium diatrizoate sufficiently in vitro to explain this action of CM. These results indicate a pharmacological action by i.v. CM that may require special attention when reduced CSF production would be deleterious.

The Tn3-encoded resolvase protein promotes a site-specific recombination reaction between two directly repeated copies of the recombination site res. Several inhibitors that block this event in vitro have been isolated. In this study four of these inhibitors were tested on various steps in the recombination reaction. Two inhibitors. A9387 and A1062, inhibit resolvase binding to the res site. Further, DNase I footprinting revealed that at certain concentrations of A9387 and A1062, resolvase was preferentially bound to site I of res, the site containing the recombinational crossover point. The two other inhibitors, A20812 and A21960, do not affect resolvase binding and bending of the DNA but inhibit synapse formation between resolvase and two directly repeated res sites.