Several monomethylated derivatives of a-(N)-heterocyclic carboxaldehyde thiosemicarbazones were prepared to define the molecular dimensions compatible with antineoplastic activity. These were the thiosemicarbazones of 3-, 4-, and 5-methylisoquinoline-l-carboxaldehyde and of 3-, 4-, 5-, and 6-methylpyridine-2-carboxaldehyde. Tests for tumor-inhibitory potency indicate that in general the pyridine derivatives were better inhibitors of the growth of the LI210 lymphoma than were the isoquinolines. Introduction of a 6-Me group in the pyridine ring and of an analogous 3-Me substituent in the isoquinoline structure resulted in compounds with no antineoplastic activity indicating an apparent intolerance to substitution at the a position to the heterocyclic N atom for inhibitory action. Me substituents at the other positions of these ring systems did not significantly increase the carcinostatic potency of the parent compounds.
A fundamental principle of pharmacology is that a relationship exists between a drug's action and its concentration at the site of that action. Pharmacokinetic studies attempt to quantify this relationship by measuring the concentration of the drug in an accessible body¯uid. Traditionally, the body¯uids most conveniently sampled for this purpose are blood, plasma, urine and cerebrospinal¯uid. In the study of drugs active in the alimentary tract, it may be useful to measure their concentrations at the site of action.Sampling methods include biopsy of the intestinal mucosa to measure a drug's tissue concentration, 1, 2 but this technique requires endoscopy, with its attendant risks, the amount of tissue obtained is small and mucosal oedema from in¯ammation may dilute the local tissue concentration. Analysis of drug concentration in stool, speci®cally the faecal water component of stool, is also possible, but variations in the volume and hydration of stool limit the precision of this technique.In this report, we propose and validate an alternative technique for sampling the luminal extracellular¯uid of the large intestine for quantitative drug analyses, dialysis of the rectum. This procedure is a derivation of the technique of in vivo dialysis of faeces, introduced by Wrong in the 1960s. 3, 4 Dialysis of faeces has been used SUMMARY Background: It is useful to measure the luminal concentration of drugs which act in the gut. Dialysis of the rectum has not previously been used or validated for this purpose. Aim: To determine the precision of rectal dialysis for measuring rectal drug concentrations. Methods: To establish the duration of dialysis required to approach equilibrium, the rate of methotrexate diffusion into dialysis bags was ®rst determined in vitro. The precision of rectal dialysis for sampling the methotrexate concentration of colonic lumen extracellular¯uid was determined in seven subjects who underwent two consecutive dialysis procedures. Subjects treated with subcutaneous methotrexate for refractory in¯ammatory bowel disease were studied.
Abstract-A simplified method is presented to calculate moments of failure time and residual lifetime of a fault-tolerant system. The method is based on recent results in queueing theory. Its effectiveness is illustrated by considering a dual repairable system from the literature.
This paper is a comparative study of two switching schemes for isotropic networks, namely, single hop and cut-through communication schemes. The comparison between the two is based on the time delay for a packet to go through a given path, characterized by the number of links between source and destination. Each sclieme is modeled by a discrete Markov chain. The research results show how the performance of the communication schemes depend on the path length, the load on the communication network and the error rate. As expected, the cut-through communication scheme is considerably better than the single hop communication sclicrne when the communication load is light. However, as the load increases, the performance of the cut-through scheme deterie I ates inore rapidly than the single hop, until they are comparable. \\'hen the load is very heavy, the two performance curves actually cross very close to 1 -3 p , so the single hop comnunication scheme works better. The error rate plays a crucial role in the communication process. The time delay becomes infinite when the throughput approaches 1 -p. We present simple formulas for all the analysis.
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