Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.     

Random primed polymerase chain reaction differentiates Codonopsis pilosula from different localities

DNA fingerprints distinctive among the samples from different localities in China were successfully reproduced for the Chinese herb Dangshen, the roots of CODONOPSIS PILOSULA, (Campanulaceae). Similarity index (S.I.) analysis revealed that C. PILOSULA samples from the same province generated similar DNA fingerprints, while samples of different provinces displayed different DNA fingerprints. This method may be a general and valuable tool for locality authentication of other Chinese herbal medicinal materials.     

Clinical applications of power spectral analysis of electromyographic investigations in muscle function

Electromyographic (EMG) power spectral analysis of the electrical signals produced by a contracting muscle is emerging as a useful clinical tool. It has the potential to measure objectively the fatigue rate of individual muscles during an exertion. This technical note gives a simple introduction to the spectral changes of the EMG signals during fatigue. It outlines the technical aspects of EMG investigations including the data collection, signal analysis and its interpretation. The clinical applications, its present limitations and future applications are also given. The correct use and interpretation of the power spectral analysis in the clinical environment is important for its further development as a clinical measurement.     

Doppler sonographic detection of reverse twin-twin transfusion after intrauterine death of the donor

We report a "stuck" twin, in which a reverse blood shunt from the recipient to the donor was detected by Doppler sonography after death of the donor. This acute reverse transfusion caused intrauterine fetal distress and severe neonatal anemia of the surviving recipient. We believe that acute hemodynamic change after death of one fetus, in addition to causing a derangement in coagulation, causes immediate danger or subsequent organ damage for the surviving co-twin.     

Reduction of adrenocorticotropic hormone (ACTH) and cortisol in drug addicts treated by acupuncture and electrical stimulation (AES).

Forty-two heroin addicts and 31 normal persons were examined for the effect of acupuncture and electrical stimulation (AES) on plasma ACTH, cortisol and cyclic-AMP levels. Both ACTH and cortisol levels were reduced significantly in the addicts after treatment whereas no such significant reduction was observed in the normals. Plasma cyclic-AMP level was not affected in either group. Taken together, results from the present study suggest that the mechanism of AES in the treatment of addiction may have a neuroendocrinological basis. This hypothesis is particularly attractive in view of the isolation of opiate-like peptides from the brain.     

Performance characteristics of a gamma camera over a wide range of energies

The problem of choosing which collimator to use for imaging a new isotope has been approached by collecting resolution and sensitivity data for a selected group of isotopes. These have been chosen to be readily available and to have generally a single -ray only. Resolution and sensitivity plots for a low energy collimator and a high energy collimator are presented and their use with several isotopes of interest is discussed. The interpretation of recommendations in the literature on the choice of collimators for newly introduced isotopes would be considerably simpler if data in this format were commonly available.     

Attenuation of voluntary ethanol consumption by dopamine-beta-hydroxylase inhibition (FLA-57): mediated by changes in aversion, reinforcement or both

The dopamine-beta-hydroxylase inhibitor, FLA-57, was reported by several investigators to reduce voluntary ethanol consumption in rats. The nature of the effect of FLA-57 on this behavior had been attributed to its involvement in both the mediation of positive reinforcing and aversive processes. In the present study, the capacity of FLA-57 to induce a conditioned taste aversion (CTA) in both a forward and a "nominally backward conditioning" paradigms was investigated. This was done in an attempt to assess the possible contribution of a FLA-57-induced CTA to the previously observed reduction in ethanol intake in several drinking studies. Furthermore, the ability of FLA-57 to induce a CTA in a nonnovel situation, where the taste of the presented solution (ethanol or saccharin) was familiar to the animals, was also assessed. The inclusion of these specific conditions was necessitated by the attempt to create conditions similar to those prevalent in drinking studies. We found that FLA-57, in both conditioning paradigms, induced a significant CTA. Animals, naive and experienced with the taste of ethanol or saccharin, exhibited a CTA following the administration of FLA-57. However, the magnitude and rate of extinction of the observed CTAs did not resemble those observed in studies on the effects of FLA-57 on ethanol intake. The results of this study suggest that while it is possible that FLA-57 exerts its effect on ethanol intake, at least in part, through an aversive mechanism, such a mechanism is unlikely to be the exclusive process through which ethanol ingestion is attenuated.     

Review of methods & simulators for evaluation of noninvasive blood pressure monitors

Automated noninvasive blood pressure (NIBP) monitors have found widespread use both inside and outside clinical environments in recent years. Present methods for evaluating the measurement accuracy of this class of devices involve population studies that are meticulous, time-consuming and costly. These methods are also impractical for routine evaluation. NIBP simulators offer an alternative approach to evaluating automated NIBP monitors without directly using human subjects. They enable evaluation to be carried out on demand with little training, providing a safe and convenient way for manufacturers and hospitals to validate the performance of both new and existing monitors.