Quantitative evaluation of the relaxivity effects of iodine on GD-DTPA enhanced MR arthrography

PURPOSE: To quantify the effect of iodine on the gadolinium (Gd) contrast-enhanced signal in MR arthrography. MATERIALS AND METHODS: Saline solutions of Gd contrast agent (0-1 mmol/liter) were mixed with iodinated contrast agent (0-185 mmol/liter). The T1 and T2 relaxation constants of these solutions were measured at 1.5T. Different types of commonly used iodinated contrast agents as well as sodium iodide (NaI) solutions were also analyzed. RESULTS: Iodine caused significant T2 shortening and some T1 shortening in Gd contrast solutions. Both contrast agents independently obeyed the standard relaxation relation, and their mixture obeyed a modified version of this relation. The side chains in various iodine molecules and their viscosities affected the relaxation properties differently. For various spin-echo (SE) sequences, the signal from synovial fluid containing different concentrations of the two contrast agents was calculated. The T2-weighted signal appeared to be most affected by the increase in iodine concentrations. In the absence of Gd contrast, all SE sequences showed an initial increase in signal from iodine contrast. CONCLUSION: A generalized relation for the relaxivities of Gd contrast in the presence of iodine was established. The side chains of iodine contrast were found to alter the relaxivities of Gd contrast. Imaging with proton density (PD)-weighted SE with only iodine contrast agent was found to be feasible.     

De novo discovery of serotonin N-acetyltransferase inhibitors

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) is a member of the GCN5 N-acetyltransferase (GNAT) superfamily and catalyzes the penultimate step in the biosynthesis of melatonin; a large daily rhythm in AANAT activity drives the daily rhythm in circulating melatonin. We have used a structure-based computational approach to identify the first druglike and selective inhibitors of AANAT. Approximately 1.2 million compounds were virtually screened by 3D high-throughput docking into the active site of X-ray structures for AANAT, and in total 241 compounds were tested as inhibitors. One compound class, containing a rhodanine scaffold, exhibited low micromolar competitive inhibition against acetyl-CoA (AcCoA) and proved to be effective in blocking melatonin production in pineal cells. Compounds from this class are predicted to bind as bisubstrate inhibitors through interactions with the AcCoA and serotonin binding sites. Overall, this study demonstrates the feasibility of using virtual screening to identify small molecules that are selective inhibitors of AANAT.     

The natural history of smoking.

This study is a small collection of the natural history of smoking of 865 persons - all smokers and majority (97.11%) of them were males, more than 80% were between 21-50 years, most (90%) were Hindus and 75% were service holders. It revealed that most of the subjects started smoking between 10 and 25 years of age, frequently being requested by their friends but felt nothing mentionable at their first experience. Most of them (64%) were smoking for more than 10 years, 48.56% were smoking more than 10 cigarettes in a day, filter-tipped more often (by 64% subjects) and without any history of break by 56% subjects. Majority (80%) used to inhale the smoke and 40% had no specific time of choice. Most of the subjects (80%) like to smoke in deep thoughts, 66% during excitement, 60% when depressed, 82% when relaxed and 62.5% when alone. But most of them (64%) did not smoke when busy. Majority (70.87%) felt relaxed when smoking. Most of the people (45%) stood reasonable having no cigarette in their stock. Majority (84%) used to smoke even when not offered. Tobacco was consumed largely as smoke by 75% subjects; 78% subjects smoked only cigarettes and about half of the smokers smoked even when they did not enjoy it.     

Supersensitivity of spinal dopaminergic receptors in rat after chronic haloperidol.

In order to examine the effect of chronic neuroleptics on spinal dopaminergic system, rats were treated with haloperidol (0.5 mg/kg IP) for 21 days and the monosynaptic mass reflex (MMR) as well as dopamine (DA) metabolism were investigated. MMR, recorded from ventral root L6 following supramaximal stimulation to ipsilateral dorsal root L6 in spinalized rats, were found to be unaffected following chronic haloperidol treatment when compared to control. Apomorphine (0.1 mg/kg IV) caused 10-20% depression of MMR in control animals which was augmented to 40-50% in chronically haloperidol-treated animals suggesting an upregulation of DA receptors in the spinal cord. DA content of lumbar region of the spinal cord was unaffected whereas its major metabolite, homovanillic acid, was significantly reduced in chronic haloperidol-treated animals. This decreased utilization of DA may compensate the upregulation of DA receptors to maintain the physiological homeostasis of the spinal dopaminergic system.     

Hepatic clearance and biliary secretory rate maximum of taurocholate in the recirculating and single pass isolated perfused rat liver. Effects of the cholestatic agent, estradiol-17 beta-(beta-D-glucuronide)

The ability of the cholestatic steroid glucuronide, estradiol-17 beta-(beta-D-glucuronide) (E(2)17G), to inhibit the hepatic clearance (ClH) and biliary secretory rate maximum (SRm) of taurocholate was investigated in the recirculating and single pass isolated perfused male rat liver. In the recirculating perfused liver, E(2)17G (0, 2, 4, or 6 mumol) was added as a bolus dose to the reservoir at zero time while taurocholate was infused into the portal vein in increasing amounts (15, 30, 45, or 60 mumol/mL; 1 mL/hr for 15 min each). E(2)17G (4 mumol) caused a significant (P less than 0.05) inhibition of bile flow and bile acid secretion at 10-15 min during infusion of 15 mumol/hr taurocholate but did not inhibit the SRm which occurred at 42 min, indicating that E(2)17G had not caused an irreversible inhibition of taurocholate transport. E(2)17G (6 mumol) caused a profound and irreversible inhibition of bile flow attributable to retention of E(2)17G in the liver. The noncholestatic estradiol-3-(beta-D-glucuronide) (E(2)3G; 6 mumol) had no significant effect on bile flow or the SRm. In the single pass perfused liver (10 mL/min flow rate), E(2)17G (0, 1, 2, 5, or 10 nmol/mL) or E(2)3G (2 nmol/mL) was added to the perfusate resulting in a stable infusion to the liver. [3H]Taurocholate was infused into the portal vein in increasing amounts to give inflow concentrations (Cin) of 25, 50, 75 or 100 nmol/mL. In the absence of E(2)17G, taurocholate ClH decreased from 0.92 to 0.70 mL/min/g liver with increasing taurocholate concentrations. Neither E(2)17G nor E(2)3G altered the ClH of 25 nmol/mL taurocholate. E(2)17G (10 nmol/mL) inhibited bile flow and bile acid secretion first at 20-25 min, followed by inhibition of ClH of 75 and 100 nmol/mL taurocholate (35-60 min). In contrast, E(2)3G stimulated bile acid secretion and increased the SRm by 80%. Thus, at doses that did not block its own elimination, E(2)17G did not cause an irreversible inhibition of taurocholate transport into bile. E(2)17G did not directly inhibit the uptake of taurocholate into the liver but first inhibited the biliary excretion of taurocholate, resulting in its intrahepatic accumulation and decreased clearance from the perfusate.