Anticonvulsants containing the N-(3-aryl-2-propenoyl) amido pharmacophore.

A series of 1-(3-aryl-2-propenoyl)-4-oxopiperidines (1) as well as some related semicarbazones (2) and thiosemicarbazones (3) were prepared in order to determine whether the relative locations of aryl rings and amidic groups would lead to novel anticonvulsant agents. Initially the compounds were administered intraperitoneally to mice and examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens. The biodata revealed that anticonvulsant properties were displayed by most of the compounds in series (1), in half of the semicarbazones (2) while protection was absent by members of series (3). Molecular modeling was utilized in order to compare the positions of a phenyl ring in relation to amidic groups in representative compounds in series (1-3) with previously reported anticonvulsant agents. Molecular simplification of 4-oxo-1-(3-phenyl-2-propenoyl)piperidine (la) led to 1-(3-phenyl-2-propenoyl)piperidine (7) and N,N-diethylcinnamamide (8) with retention of anticonvulsant properties. Both (la) and (8) afforded protection in the hippocampal kindling screen in rats. When administered orally to rats, (la) and (8) demonstrated activity in the MES screen and in the case of (8), a huge protection index was observed revealing it to be an important lead compound. The IC50 values of all of the compounds towards murine P388 cells were in excess of 50 microM while several compounds displayed cytotoxicity towards Mycobacterium tuberculosis.

Nutrient uptake by viscera drained by the portal vein in neonatal calves during intravenous infusion of glutamine.

OBJECTIVE: To quantify glutamine use by viscera drained by the portal vein in neonatal calves and to determine whether uptake could be stimulated by long-term IV infusion or long-term use of oral supplements. ANIMALS: 4 healthy neonatal calves. PROCEDURE: A femoral artery, jugular vein, and the portal vein were surgically cannulated in each calf. Blood flow in the portal vein was measured, using an ultrasonic transit-time flow probe. Calves were given an IV infusion of glutamine on days 6, 8, and 10 after surgery. Before the first infusion, calves were fed a diet of milk only. The diet was supplemented with glutamine for the second and third infusions. Glutamine was administered via the jugular vein during a 5-hour period. Venous and arterial blood samples were collected every hour for 5 hours. RESULTS: During glutamine infusion, uptake of glutamine by viscera drained by the portal vein increased in association with increased production of ammonia. Glutamine supplementation of the diet did not alter glutamine uptake. Glutamine infusion did not increase viscera uptake of indispensable amino acids. Long-term use of glutamine supplements or infusion of glutamine for periods of more than 1 hour increased glutamine uptake by viscera. Arterial leucine concentration and uptake of leucine by the viscera decreased during glutamine infusion, indicating that leucine became the limiting factor. CONCLUSION: Glutamine administration (supplements or infusions) to calves may require that a mixture of amino acids be provided to improve effectiveness. CLINICAL RELEVANCE: Glutamine may be beneficial in treatments designed to promote intestinal healing in diarrheic calves.

Development of a heating device for sampling arterialized venous blood from a hand vein.

A practical and safe heating device for sampling arterialized venous blood from a hand vein was constructed and tested under experimental conditions. Blood chemistry values (pH, pCO2, pO2 and O2 saturation) were measured in nine individuals from blood sampled from an antecubital vein and a hand vein, as well as from a hand vein that had been heated in the handwarmer. Only blood sampled from the heated hand vein gave blood gas values that were consistently in the arterial range. Mean blood gas values were 38.0 +/- 2.5 mmHg, 79.8 +/- 6.8 mmHg and 95.7 +/- 0.9% for pCO2, pO2 and O2 saturation, respectively, for blood sampled from the heated hand vein. No significant difference (P greater than 0.05) was evident in blood gas values whether blood was sampled 15, 30, 45, 60, 75 or 90 min after placing the hand in the heated handwarmer. The handwarmer enables arterialized venous blood sampling after 15 min of warming and is safe to use in any experimental or clinical situation where sampling from an artery is impractical.